Currently Enrolling Studies

ARTEMIS / Adverum / ADVM-022-12

A Multi-Center, Randomized, Double-Masked, Active-Comparator-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Ixoberogene soroparvovec (Ixo-vec) in Participants with Neovascular Age-Related Macular Degeneration

Inclusion Criteria

• Able and willing to provide informed consent (or have a legally authorized representative who is able and willing to provide informed consent) prior to any study assessments and procedures and comply with the study requirements and visits
• Male or female with a diagnosis of CNV secondary to nAMD in the study eye, with nAMD disease activity (i.e., any fluid [IRF or SRF] present on SD-OCT) at Screening Visit 1 (Day -56 to -49)
• At least 50 years old at Screening Visit 1 (Day -56 to -49)
• ETDRS BCVA letter score ≥ 35 and ≤ 78 (approximate Snellen equivalent of 20/200 to 20/32) in the study eye at Screening Visit 1 (Day -56 to -49) with no loss of vision ≥ 5 ETDRS letters from Screening Visit 1 (Day -56 to -49) to Day 1
• ETDRS BCVA letter score ≥ 35 (approximate Snellen equivalent of 20/200 or better) in the non-study eye at Screening Visit 1 (Day -56 to -49)

• Demonstrated a meaningful anatomic response to anti-VEGF therapy, as determined by the CRC based on SD-OCT images of the study eye collected at Screening Visit 1 (Day - 56 to Day -49) and at Day 1. A meaningful anatomic response is defined as either:

  • Complete resolution of fluid (SRF/IRF) at Day 1, OR

  • Reduction in CST at Day 1 from Screening Visit 1 (Day -56 to Day -49) of:  

    • 10% for participants with CST > 300 μm at Screening Visit 1

    • 5% for participants with CST ≤ 300 μm at Screening Visit 1

• Able to reliably use eye drops per protocol, according to the Investigator’s judgment

• Women of childbearing potential (i.e., postmenarcheal, has not reached a postmenopausal state [> 12 continuous months of amenorrhea with no identified cause other than menopause], or has not undergone surgical sterilization [removal of both ovaries and/or uterus]) must have a negative pregnancy test during screening and agree to use an acceptable form of contraception that results in a failure rate < 1% per year (e.g., bilateral tubal ligation; surgical sterilization of the participant’s sole male partner; oral, implantable, or injectable hormonal contraceptives that inhibit ovulation; hormone-releasing intrauterine devices; copper intrauterine devices) or agree to remain abstinent (refrain from heterosexual intercourse). Of note, contraception methods that do not result in a failure rate of < 1% per year (e.g., male or female condom with or without spermicide; cap, diaphragm, or sponge with spermicide) are not acceptable. The reliability of sexual abstinence should be evaluated in relation to the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception

• Sexually active male participants must agree to use an acceptable form of contraception that results in a failure rate < 1% per year during the study, if their female partners are of childbearing potential

General Exclusion Criteria

• History of a medical condition (systemic disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding) giving reasonable suspicion of a condition that contraindicates the use of Ixo-vec, compromises the participant’s ability to comply with the planned study activities, or that might affect the interpretation of the results of the study or render the participant at high risk for treatment complications in the opinion of the Investigator. History of severe COVID-19 infection may meet this exclusion criteria if, in the opinion of the Investigator, it is likely to lead to any of the complications listed above.

• Received any prior gene therapy
• Received any non-gene therapy IMP or medical device in the study eye within 3 months of Screening Visit 1 (Day -56 to Day -49) or 5 half-lives of the IMP prior to dosing with Ixo-vec, whichever is longer
• History of allergy, hypersensitivity, or contraindications to the use of any product or its excipients administrated within this protocol including aflibercept, corticosteroids (i.e., difluprednate), or fluorescein dye or sodium fluorescein used in angiography (mild allergy amenable to treatment is allowable)
• Evidence of poorly controlled diabetes or glycated hemoglobin (HbA1c) ≥ 8.0% from Screening Visit 1 (Day -56 to Day -49) to Week 1
• Female participants who are pregnant or breastfeeding or who intend to become pregnant or breastfeed in the future

• History or evidence of any of the following cardiovascular diseases:

  • Myocardial infarction in the 6-month period prior to Day 1

  • Uncontrolled hypertension defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg, despite using blood pressure-lowering medication within the screening period. If blood pressure-lowering medications are required, participant should be on a stable dose of the same medication continuously for 30 days prior to Day 1

  • Stroke in the 6-month period prior to Day 1

• Any history of ongoing bleeding disorders. The use of aspirin or other anticoagulants (e.g., Factor Xa inhibitors) is permitted
• Use of systemic immunosuppressive drugs (e.g., intravenous steroids, methotrexate, azathioprine, cyclosporin, secukinumab, denosumab, and anti-tumor necrosis factors [TNFs], such as adalimumab, infliximab, etanercept) within the 90 days prior to Screening Visit 1 (Day -56 to Day -49). Low stable doses of corticosteroids (defined as ≤ 10 mg prednisolone / prednisolone or equivalent dose) are permitted, as well as any inhaled, nasal or dermal steroid use
• Received anti-VEGF IVT injection in the study eye within 28 days prior to Screening Visit 1 (Day -56 to -49) or systemic anti-VEGF therapy during the 3-month period prior to Screening Visit 1 (Day -56 to Day -49).

• History of malignancy within the 5 years prior to Screening Visit 1 (Day -56 to Day -49), except for the following adequately treated:

  • Local basal cell or squamous cell carcinoma of the skin

  • Carcinoma in situ of the cervix or breast

  • Papillary, non-invasive bladder cancer

  • Prostate cancer Stage 1 and 2 for which observation is clinically indicated with stable prostate-specific antigen for 6 months

  • Any other cancer that has been in complete remission for at least 2 years or considered surgically cured

• Positive for human immunodeficiency virus (HIV) infection or hepatitis B or C virus at Screening Visit 1 (Day -56 to Day -49) unless having received a documented cure for hepatitis C virus.
• History of COVID-19 or syphilis within 6 weeks prior to Week 1
• Any febrile illness within 1 week prior to Day 1

Ocular Exclusion Criteria

• Any active ocular or periocular infection (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in the study eye from Screening Visit 1 (Day -56 to Day -49) to Week 1
• Evidence of the total area of scar or macular fibrosis making up ≥ 50% of the total lesion area, atrophy, or other structural damage in the center of the fovea in the study eye as confirmed by the CRC at Screening Visit 1 (Day -56 to Day -49)
• Central subfield of the study eye affected by fibrosis or geographic atrophy, assessed by color fundus photography (CFP) at Screening Visit 1 (Day -56 to Day -49) and confirmed by the CRC
• Evidence of subretinal hemorrhage that is either 50% or more of the total lesion area, or if the blood is under the fovea and is ≥ 1 disc area in size in the study eye, as confirmed by the CRC at Screening Visit 1 (Day -56 to Day -49) (if blood is under the fovea, fovea must be surrounded 270 degrees by visible CNV)
• Any history or evidence of a concurrent intraocular condition in the study eye, including retinal diseases other than nAMD, that, in the judgment of the Investigator, could reduce the potential for visual improvement, confound assessment of the macula or require medical or surgical intervention during the study

• History or evidence of the following in the study eye:

  • Intraocular or refractive surgery within 90 days prior to Screening Visit 1 (Day -56 to Day -49)

  • Any previous penetrating keratoplasty or vitrectomy

  • Any previous panretinal photocoagulation

  • Any previous submacular surgery, other surgical intervention (including port delivery system) or laser treatment for age-related macular degeneration

• Any history or evidence of retinal detachment (with or without repair) or retinal pigment epithelium rip/tear in the study eye, as determined by the Investigator during screening or at Day 1
• Aphakia and/or complete or partial absence of posterior capsule at Screening Visit 1 (Day -56 to Day -49) or cataract extraction or yttrium aluminum garnet (YAG) laser capsulotomy in the study eye within 3 months prior to Screening Visit 1 (partial absence of the posterior capsule due to YAG laser capsulotomy performed > 3 months prior to Screening Visit 1 is acceptable)
• Uncontrolled ocular hypertension or glaucoma in the study eye from Screening Visit 1 (Day -56 to Day -49) to Week 1 (defined as IOP > 22 mmHg despite treatment with antiglaucoma medication, or according to Investigator’s judgment) or current use of ≥ 2 IOP lowering medications or normal tension glaucoma/suspect in the study eye
• Any history of IOP elevation related to topical steroid administration in either eye
• Any history of uveitis or inflammation (grade trace or above) except mild anticipated post-operative inflammation that resolved in either eye
• Any history of intraocular or periocular steroid treatment for any ocular condition (e.g., IVT Triesence®, Iluvien®, or Ozurdex®) within 6 months prior to Screening Visit 1 (Day -56 to Day -49)

• Any history of treatment with complement inhibitors (e.g., pegcetacoplan and avacincaptad pegol) for geographic atrophy in the study eye

• Known history of ocular herpes simplex virus, varicella-zoster virus, or cytomegalovirus, including viral uveitis, retinitis, or keratitis in either eye
• Previous therapeutic radiation near the region of the study eye

Belvedere / Genentech / ML43000

A PHASE IV, MULTICENTER, OPEN-LABEL STUDY TO ASSESS CORNEAL ENDOTHELIAL CELLS IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATED WITH THE PORT DELIVERY SYSTEM WITH RANIBIZUMAB (PDS)

General Inclusion Criteria

• Age > 50 years, at the time of screening
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures

Study Eye Inclusion

• Initial diagnosis of nAMD < 18 months prior to screening
• Difference of < 10% in ECD at screening between the 2 eyes as measured by specular microscopy and determined by the independent reading center
• Availability of historical VA data and SD-OCT imaging prior to the first anti-VEGF IVT for nAMD
• Availability of comprehensive historical anti-VEGF injection data including anti-VEGF agent administered and date of administration from the first anti-VEGF treatment for nAMD
• Demonstrated response to at least two prior anti-VEGF intravitreal injections since diagnosis, as evidenced by the following:
  • Overall decrease in nAMD disease activity detected on screening SD-OCT as assessed by the investigator and confirmed by the central reading center
  • Stable or improved BCVA
• BCVA of 34 letters (approximate 20/200 Snellen equivalent) or better
• All subtypes of nAMD lesions are permissible
• nAMD lesions at the time of diagnosis must involve the macula (6 mm diameter centered at the fovea)

Exclusion Criteria Study Eye

• Prior treatment with verteporfin for injection, external-beam radiation therapy, or transpupillary thermotherapy
• Previous treatment with corticosteroid intravitreal injection
• Previous laser (any type) used for AMD treatment
• History of vitreous hemorrhage
• History of rhegmatogenous retinal detachment
• History of corneal transplant
• History of conjunctival surgery in the superotemporal quadrant

Exclusion Criteria Both Eyes

• Previous PDS implantation
• Previous intraocular surgery (including cataract surgery) within 6 months of study enrollment
• Prior vitrectomy surgery, submacular surgery, or other surgical intervention for AMD
• Prior pars plana vitrectomy surgery
• Previous intraocular device implantation excluding intraocular lenses
• History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
• Prior participation in a clinical trial involving any intravitreal anti-VEGF agents
• Intraocular laser therapy including selective laser trabeculoplasty, yttrium-aluminum garnet (YAG), prophylactic peripheral iridotomy within 1 year of screening, or YAG capsulotomy within 3 months of screening
• Contact lens wear in either eye within 2 months of screening
• Any prior ocular trauma (blunt or penetrating)
• History of corneal transplantation, including partial-thickness corneal grafts (e.g., Descemet membrane endothelial keratoplasty, Descemet stripping endothelial keratoplasty)
• Prior treatment with brolucizumab
• Prior treatment with any anti-VEGF biosimilar agents
• Prior treatment with faricimab within 2 months of screening
• Prior treatment with aflibercept 8 mg within 2 months of screening
• Prior treatment with external-beam radiation therapy or brachytherapy

Macular Neovascularization Lesion Characteristics

• Study Eye
  • Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is greater than 0.5-disc area (1.27 mm2) in size
  • Subfoveal fibrosis or subfoveal atrophy
• Either Eye
  • MNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
  • MNV masquerading lesions (e.g., cone dystrophy, adult vitelliform dystrophy, pattern dystrophy)

Exclusionary Concurrent Ocular Conditions

• Study Eye
  • Retinal pigment epithelial tear
  • Retinal tears or peripheral retinal breaks on depressed fundus examination that are untreated, or treated within the 3 months prior to study enrollment
  • Previous violation of the posterior capsule is also an exclusion criterion unless it occurred as a result of YAG laser posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation
  • Spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia or evidence of pathologic myopia on depressed fundus examination
  • Preoperative refractive error that exceeds 8 diopters of myopia, for patients who have undergone prior refractive or cataract surgery
  • Spherical equivalent of the refractive error demonstrating more than 5 diopters of hyperopia
  • Preoperative refractive error that exceeds 5 diopters of hyperopia, for patients who have undergone prior refractive or cataract surgery
  • Uncontrolled ocular hypertension or glaucoma (defined as intraocular pressure [IOP] > 25 mmHg or a cup-to-disc ratio > 0.8, despite treatment with antiglaucoma medication) and any such condition the investigator determines may require a glaucoma-filtering surgery during a patient’s participation in the study
  • Scleral pathology in the superotemporal quadrant (e.g., scleral thinning or calcification)
  • Conjunctival pathologies (e.g., pterygium, scarring, thinning, fibrosis) in the superotemporal quadrant
  • History or presence of severe posterior blepharitis, recurrent chalazia or hordeolum, severe dry eye syndrome, or severe allergic conjunctivitis
  • Ectropion, entropion, or other impairment of the upper or lower eyelid impacting lid functionality needed to protect the ocular surface from exposure
  • Trichiasis
  • Corneal neuropathy
  • Lagophthalmos or incomplete blink
  • Active or history of facial nerve palsy/paresis
• Non-Study Eye
  • Concurrent PDS implantation
• Either Eye
  • Aphakia or absence of the posterior capsule
  • Any concurrent intraocular condition (e.g., cataract, glaucoma, diabetic retinopathy, or epiretinal membrane) that would either require surgical intervention during the study to prevent or treat visual loss that might result from that condition or affect interpretation of study results
  • Corneal ECD < 1500 cells/mm2 in either eye at screening as determined by the independent reading center
  • Fuchs endothelial corneal dystrophy Grade > 2
  • Previous corneal endothelial cell damage, including from blunt or surgical trauma (including complicated cataract surgery resulting in complicated lens placement such as anterior chamber intraocular lens, sulcus intraocular lens, or aphakia)
  • Any ocular condition that precludes obtaining an analyzable specular microscopy image
  • Active or history of corneal edema
  • Active or history of corneal dystrophies
  • Active or history of iridocorneal endothelial syndrome
  • Active or history of pseudoexfoliation syndrome
  • Active or history of herpetic keratitis or kerato-uveitis (including herpes simplex virus and herpes zoster virus)
  • Any active or history of uveitis (e.g., idiopathic, drug-associated or autoimmune-associated)
  • Active or history of keratitis, scleritis, or endophthalmitis
  • Active ocular or periocular infection (i.e., conjunctivitis, dacryocystitis)
  • Active or history of Sjogren’s syndrome or keratoconjunctivitis sicca
  • Active or history of floppy eyelid syndrome
  • Active or history of chronic eye rubbing
  • Active thyroid eye disease

Concurrent Systemic Conditions

• History of uncontrolled blood pressure (defined as systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 110 mmHg, while a patient is at rest)
• Active or history of autoimmune diseases, such as rheumatoid arthritis, lupus, granulomatosis with polyangiitis (Wegner’s)
• History of stroke within the last 3 months prior to screening
• Uncontrolled atrial fibrillation within 3 months of screening
• History of myocardial infarction within the last 3 months prior to screening
• History of other disease, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the implant and that might affect interpretation of the results of the study or renders the patient at high risk of treatment complications, in the opinion of the investigator
• Current active systemic infection
• Use of any systemic anti-VEGF agents
• Chronic use of oral corticosteroids (>10 mg/day of prednisone or equivalent)
• Active cancer within 12 months of enrollment except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of < 6 and a stable prostate-specific antigen for > 12 months
• Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month prior to screening (excluding vitamins and minerals)
• Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of the screening visit

Burgundy / Genentech / BP41670

A THREE-PART, PHASE I STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND EFFICACY OF ZIFIBANCIMIG FOLLOWING INTRAVITREAL ADMINISTRATION OF MULTIPLE ASCENDING DOSES AND CONTINUOUS DELIVERY FROM THE PORT DELIVERY IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION (BURGUNDY)

General Inclusion Criteria

• Willing to allow AH collection
• Age > 50 years, at the time of signing the informed consent

Study Eye Inclusion

• CNV exclusively due to AMD and with the following characteristics:
  • Active CNV lesions must be subfoveal or juxtafoveal with a subfoveal component related to CNV activity (e.g., subretinal fluid, intraretinal fluid, retinal pigment epithelium (RPE) detachment, etc.) at the time of screening (as assessed by the central reading center).
  • All subtypes of CNV are permissible
• Diagnosis of nAMD within nine months prior to the screening visit
• Previous treatment with at least two IVT anti-VEGF or anti-VEGF/Ang-2 administrations for nAMD per SoC within six months prior to the screening visit. The last IVT administration must have occurred at least 21 days prior to the screening visit
  • If a participant did not receive at least two IVT anti-VEGF or anti-VEGF/Ang-2 administrations as described above but is otherwise eligible for the study, the participant can be treated in a run-in period to meet this specific criterion
• Demonstrated response to prior IVT anti-VEGF or anti-VEGF/Ang-2 treatment since diagnosis, as evidenced at screening by the following:
  • Previous decrease in nAMD disease activity detected on SD-OCT, as assessed by the Investigator and confirmed by the central reading center AND
  • Previously stabilized or improved BCVA (as assessed by the Investigator)
• Availability of historical VA data prior to the first anti-VEGF or anti-VEGF/Ang-2 treatment for nAMD until the time of study enrollment
• Decreased BCVA attributable primarily to nAMD with letter score of 78 to 34 letters (inclusive) on ETDRS-like charts at screening. In case both eyes of a participant are eligible, the study eye selection is at the Investigator’s discretion

Exclusion Criteria Study Eye

• History of vitrectomy surgery, submacular surgery, other intraocular surgery, or any planned surgical intervention during the study period
• Cataract surgery without complications within three months preceding the screening visit or planned during the study period. Cataract surgery with complications falls under Exclusion Criterion 1.
• Prior macular treatment with verteporfin, external beam radiation therapy, transpupillary thermotherapy, or any type of laser photocoagulation
• Subretinal hemorrhage > 50% of the total lesion area and/or involving the fovea
• Retinal pigment epithelial tear involving the macula
• History of vitreous hemorrhage
• History of rhegmatogenous retinal detachment
• History of rhegmatogenous retinal tears or peripheral retinal breaks within three months prior to the screening visit
• Any concurrent intraocular conditions (e.g., cataract, diabetic retinopathy, epiretinal membrane with traction, macular hole) that, in the opinion of the Investigator, could either:
  • Require medical or surgical intervention during the study period to prevent or treat visual loss that might result from that condition; or
  • Likely contribute to loss of BCVA over the study period if allowed to progress untreated; or
  • Preclude any visual improvement due to substantial structural damage
• Actual or history of myopia > -8 diopters
• Uncontrolled ocular hypertension or glaucoma (defined as IOP >25 mm Hg or a cup to disc ratio > 0.8, despite treatment with antiglaucoma medication) and any such condition the Investigator determines may require a glaucoma-filtering surgery during a participant’s participation in the study
• History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
• History of corneal transplant
• Prior treatment with any medication for geographic atrophy.
• Prior treatment with any anti-VEGF-C or anti-VEGF-D inhibitors

Fellow Eye Exclusion

• BCVA letter score using ETDRS charts of < 34 letters
• Treatment with anti-VEGF or anti-VEGF/Ang-2 agents within one month prior to Day 1.

Either Eye Exclusion

• CNV due to causes other than nAMD, such as ocular histoplasmosis, trauma, pathological myopia, angioid streaks, choroidal rupture, uveitis or central serous chorioretinopathy
• Active intraocular inflammation (grade trace or above), infectious conjunctivitis, keratitis, scleritis, or endophthalmitis.
• History of uveitis, including history of any intraocular inflammation following IVT anti-VEGF or anti-VEGF/Ang-2 injections
• Prior treatment with brolucizumab         
• Prior gene therapy for nAMD

Concurrent Systemic Conditions Exclusions

• Uncontrolled blood pressure ([BP] defined as systolic > 180 mm Hg and/or diastolic > 100 mm Hg while participant at rest), at screening
• Uncontrolled atrial fibrillation within three months of screening
• History of myocardial infarction within last 12 months prior to screening
• History of stroke within last 12 months prior to screening
• Chronic use of oral corticosteroids (> 10 mg/day of prednisone or equivalent).
• Current systemic treatment for a confirmed active systemic infection
• Bleeding disorders, including platelet disorders, acquired or hereditary coagulations disorders, and acquired or hereditary vascular disorders
• Active malignancy within 12 months of screening except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of < 6 and a stable prostate-specific antigen (PSA) for > 12 months
• Any major illness or surgical procedure within one month prior to screening
• Any febrile illness within one week prior to screening or Day 1
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of the IMP or placement of the PD implant that might affect interpretation of the results of the study or renders the participant at high risk for treatment complications in the opinion of the Investigator

Galette / Genentech / GR44251

A PHASE IIa, MULTICENTER, OPEN-LABEL, SINGLE-ARM STUDY TO OPTIMIZE SUBRETINAL SURGICAL DELIVERY AND TO EVALUATE SAFETY AND ACTIVITY OF OPREGEN IN PATIENTS WITH GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION

General Inclusion Criteria

• Signed Informed Consent Form
• Age > 50 years at time of signing Informed Consent Form
• Subjects with sufficient good health that can participate in all study-related procedures and complete the study follow-up period (based on medical records)
• Ability to undergo a vitreoretinal surgical procedure under monitored anesthesia care or general anesthesia at the discretion of the investigator
• Willingness to defer donation of blood and tissues outside the context of this study for 1 year following study treatment

• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs, as defined below:

  • Women must remain abstinent or use two methods of contraception, including at least one method with a failure rate of <1% per year, for at least 6 weeks after the final dose of immunosuppressant treatment and within 1 year following subretinal surgical delivery of OpRegen, whichever is longer. Women must refrain from donating eggs during this same period

  •  A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a woman with a tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.

  • Examples of non-hormonal contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. A barrier method may be used as the second contraceptive method

  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.

• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm, as defined below:

  • With a female partner of childbearing potential who is not pregnant, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year for at least 90 days after the final dose of immunosuppressant treatment. Men must refrain from donating sperm during this same period.

  • With a pregnant female partner, men must remain abstinent or use a condom during the study and for 90 days after the final dose of immunosuppressant treatment to avoid exposing the embryo

  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form

Ocular Inclusion Criteria Study Eye:  

•  BCVA scores > 29 letters and < 60 letters (Snellen equivalent between 20/63 to 20/250) in study eye, as assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) VA chart at starting distance of 4 meters
  • If a patient’s initial BCVA score was outside the above criteria because of confounding reasons other than GA, up to two additional measurements may be taken 30 or more minutes later on the same day prior to pupil dilation or on another day during the screening period, without having to undergo re‑screening.
  • If the initial BCVA score meets the inclusion criteria but is outside the allowable range during the enrollment visit by an insignificant variation (+ 5-letter change), up to two additional measurements may be taken as above at investigator discretion
  • Only the worse-seeing eye can be selected as the study eye. However, if both eyes meet study eligibility criteria and have similar BCVA letter scores (difference between the two eyes is < 5 letters at screening), either eye can be selected according to the discretion of the investigator in consultation with the patient.
• Diagnosis of GA secondary to AMD
• Total GA lesion size > 1 mm2 and < 12.54 mm2 (approximately 0.4-5 disc area)
• GA must involve the foveal center on optical coherence tomography (OCT) images

• Pseudophakic with posterior chamber intraocular lens

  • Patients who receive subretinal cell delivery of OpRegen via suprachoroidal access without vitrectomy may be phakic as long as there is sufficient media clarity to allow evaluation of the retina and vitreous.
•    Sufficiently clear ocular media, adequate pupillary dilation, and fixation to permit quality fundus imaging

Ocular Inclusion Criteria Both Eyes:

• Diagnosis of dry AMD

Exclusion Criteria General Exclusions:

• Pregnancy or breastfeeding, or intention of becoming pregnant between enrollment and within 1 year following subretinal surgical delivery of OpRegen
  • Women of childbearing potential must have two negative serum or urine pregnancy test results, with a sensitivity of at least 25 mIU/mL, with an interval of 8 to 10 days with the second test result immediately prior to initiation of mycophenolate mofetil. If the urine pregnancy test is positive, it must be confirmed by a serum pregnancy test.

• Ongoing or previous participation in an investigational trial that involves treatment with any drug or device (with the exception of vitamins and minerals) within 6 months or 5 half-lives, whichever is longer, prior to enrollment visit 
• Previous participation in an interventional clinical trial for ophthalmic disease testing stem-cell treatments or gene therapy in either eye, regardless of timing of patient participation
• History of cognitive impairment or dementia
• Contraindication for systemic immunosuppression as utilized in the study 
• Any type of systemic disease or its treatment, in the opinion of the investigator, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk

• Currently receiving aspirin, aspirin-containing products, and/or any other coagulation modifying drugs which cannot be discontinued for an adequate time to reasonably ensure normal coagulation status at surgery.

  • Therapy can be restarted after subretinal surgical delivery of OpRegen at the discretion of the investigator.

  • The risks associated with discontinuation of coagulation modifying drug should be discussed with the patient’s primary physician at the discretion of the investigator.

• Active cancer within past 12 months prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or local prostate cancer with a stable prostate-specific antigen for more than 12 months
• Known allergy to any of the study medications or formulations

• Any active infection including, but not limited to, HIV, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV) IgM, or syphilis at screening

  • In the setting of a pandemic or epidemic, screening for active infections should be considered according to local or institutional guidelines or guidelines of applicable professional societies.

• Positive for tuberculosis (TB) during screening, defined as a positive interferon-y (IFN-y) release assay (QuantiFERON-TB Gold or equivalent)
• For patients who will receive OpRegen delivered using the Orbit SDS: metal implants or devices in or near the head, including cochlear implants, deep brain stimulators, vagus nerve stimulators, and other implanted electrodes or stimulators

Ocular Exclusions Study Eye:

• Any current or history of ocular disease other than GA that may confound assessment of the macula or affect central vision (e.g., nAMD, moderate non‑proliferative diabetic retinopathy or greater, diabetic macular edema, retinal vein occlusion, pathological myopia, macular hole)
• Vitreomacular traction or epiretinal membrane involving the fovea or disrupting the macular architecture
• History of retinal detachment
• History of any PPV, glaucoma-filtering surgery (e.g., trabeculectomy, tube-shunt surgery), or corneal transplantation

• Uncontrolled glaucoma (e.g., progressive loss of visual fields or defined as intraocular pressure [IOP] >22 mmHg at screening despite treatment with anti‑glaucoma medication) or advanced glaucoma

  • If the patient’s initial average IOP reading exceeds 22 mmHg at screening because of extenuating circumstances (e.g., forgetting or inability to take anti‑glaucoma medication as prescribed), a second reading may be taken either 30 or more minutes later on the same day or on another day during screening

• Any cataract surgery or intraocular surgery within 3 months prior to subretinal surgical delivery of OpRegen
• Any existing posterior segment device or implant, including any biodegradable/non-biodegradable implants or long-acting delivery formulations
• Ongoing or prior intraocular treatment (approved or experimental) for GA with last administration occurring within 6 months or 5 half-lives, whichever is longer, prior to the enrollment visit and during the first 18 months following surgical delivery of OpRegen
• Prior treatment with verteporfin, external-beam radiation therapy (for intraocular conditions), or transpupillary thermotherapy
• History of prophylactic subthreshold laser treatment for AMD
• History of other ocular or intraocular conditions that contraindicate the use of an investigational drug or may affect interpretation of the study results or may render the patient at high risk for treatment complications

• Any concurrent ocular condition in the study eye that, in the opinion of the investigator, could result in either of the following:

  • Require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition

  • If allowed to progress untreated, could likely contribute to loss of at least two Snellen equivalent lines of BCVA during the study period (except worsening of GA)

Ocular Exclusions Both Eyes:

• Evidence of prior or active CNV, confirmed by OCT and fluorescein angiography (FA)
• Active or history of uveitis and/or vitritis (grade trace or above), and/or scleritis in either eye
• Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis

Sienna / Bayer & Regeneron / R3918-AMD-2326-2326

A MULTICENTER, RANDOMIZED, DOUBLE-MASKED, PLACEBO-CONTROLLED PHASE 3 STUDY OF THE EFFICACY, SAFETY, AND TOLERABILITY OF SUBCUTANEOUSLY ADMINISTERED POZELIMAB IN COMBINATION WITH CEMDISIRAN OR CEMDISIRAN ALONE IN PARTICIPANTS WITH GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION

Ocular Inclusion Criteria

• Male or female ≥50 years of age at the time of signing of ICF
• Study eye with diagnosis of GA of the macula secondary to AMD not involving the foveal center point, confirmed by the CRC at screening visit 2 using multimodal imaging including FAF and SD-OCT

• Total GA area in the study eye measuring between ≥2.5 mm2 and ≤17.5 mm2, determined by screening images (assessed by CRC and confirmed at screening visit 2), and must meet all of the following criteria:

  • If multifocal, at least 1 focal lesion measures ≥1.25 mm2 (~0.5 DA)

  • Presence of perilesional hyperautofluorescence in the banded or diffuse pattern

  • GA lesion is within 1500 μm of foveal center point

  • GA lesion can be completely visualized on the macula centered FAF image

  • GA lesion can be measured separately from areas of peripapillary atrophy

• BCVA of 35 letters or better using ETDRS charts (20/200 Snellen equivalent) in the study eye at screening and randomization
• Sufficiently clear ocular media, adequate pupillary dilation and fixation to permit quality fundus imaging in the study eye at screening and randomization
• Willing and able to comply with clinic visits and study-related procedures, including completion of the full series of meningococcal vaccinations and pneumococcal vaccination required per protocol
• Provide informed consent signed by study participant
• Able to understand and complete study-related questionnaires

Ocular Exclusion Criteria

• GA in either eye due to causes other than AMD such as Stargardt disease, cone rod dystrophy or toxic maculopathies like hydroxychloroquine maculopathy
• History or current evidence of macular neovascularization and/or exudation in either eye as assessed by multimodal imaging including FA, CRC confirmed
• Prior or current IVT treatment of any kind for any indication in study eye, except approved or investigational IVT complement inhibitor therapy as long as last dose was ≥6 months prior to randomization
• Prior or current IVT treatment of any kind for any indication in fellow eye, except approved or investigational IVT complement inhibitor therapy as long as last dose was ≥6 months prior to randomization
• Prior intraocular surgery except cataract extraction or minimally invasive glaucoma surgery in study eye as long as date of these procedures was ≥3 months prior to randomization
• Prior thermal laser in the macula in either eye
• Comorbid progressive ocular condition (eg, diabetic retinopathy, macular edema, uncontrolled glaucoma, full thickness macular hole) in study eye that could affect central vision and confound study

• Any ophthalmologic condition that reduces the clarity of the media and that, in the opinion of the investigator interferes with ophthalmologic examination of the study eye (eg, advanced cataract or corneal abnormalities). Individuals should not be entered into the study if there is likelihood that they will require cataract surgery in the study eye during

  the study

Systemic Exclusion Criteria

• History or current use of systemic complement inhibitor therapy within 6 months prior to randomization or the likelihood of treatment with any such anti-complement agent during the study, with the exception of study treatments
• Known diagnosis of complement deficiency
• History of solid organ or bone marrow transplantation

• Use of chronic (>14 days) systemic corticosteroids (oral or parenteral, ≥20 mg oral prednisone or equivalent) within the previous 30 days prior to the first screening visit or during the screening period or the likelihood of chronic systemic corticosteroid treatment during the study

  • Note: The use of a short course (eg, ≤14 days) of systemic corticosteroids for anintercurrent condition is not an exclusion.

• Current or prior use of systemic immunosuppressive therapy other than corticosteroids (eg, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, cyclophosphamide, JAK inhibitors, TNF inhibitors, IL-6, IL-17, and IL-23 pathway inhibitors, etc) or the likelihood of treatment with any such agent during the study inclusive of the screening period

  • Note: the use of IL-4 or IL-13 pathway inhibitors is allowed

• History of bacterial, protozoal, viral, or parasite infection requiring systemic treatment within the previous 14 days of the screening visit including during the screening period
• Hospitalization for any infectious etiology within 3 years of screening visit #1, including but not limited to pneumonia, urinary tract infection, and cellulitis
• History of HIV infection
• Positive hepatitis B surface antigen or hepatitis C virus RNA during screening
• History of meningococcal infection

• Not meeting meningococcal vaccination requirements for participants on complement inhibitors according to latest ACIP or local guidelines (whichever is more stringent) during the screening period. Participants without prior meningococcal vaccination, or those with documented vaccination occurring greater than 5 years prior to randomization, will be eligible provided they are willing to undergo meningococcal vaccinations (ACWY conjugate and Serogroup B) prior to initiation of study treatment

• Not meeting pneumococcal vaccination requirements according to latest ACIP or local guidelines (whichever is more stringent) during the screening period. Participants without prior pneumococcal vaccination will be eligible provided they are willing to undergo pneumococcal vaccination prior to initiation of the study treatment
• Participants with known contraindication to meningococcal vaccines (ACWY conjugate and group B) and/or pneumococcal vaccine, based on local product information
• Unable to take antibiotics for meningococcal prophylaxis if required by local or national guidelines/local practice, if necessary when vaccination is less than 2 weeks from study treatment initiation, or for any other reason pertaining to risk mitigation for N. meningitidis infection
• Carrier of Neisseria meningitidis based on culture collected during screening
• Has a hemoglobin A1C ≥ 8.0% during screening. One repeat test is allowed
• Any malignancy, except for non-melanoma skin cancer or cervical/anus in-situ, that has not been resected or has any evidence of metastatic disease in the 3 years prior to the screening visit
• Anticipation of any elective surgery during the first year of the study (52 weeks) (eg, hip or knee replacement)
• Has a history of significant multiple and/or severe allergies (eg, latex gloves), or has had an anaphylactic reaction to prescription or non-prescription drugs or food
• Any medical condition or clinically significant abnormality that, in the opinion of the investigator, might interfere with the participant’s participation in the study, poses any added risk for the participant, or confound the assessment of efficacy

• Using the Modification of Diet in Renal Disease equation, has an estimated GFR <30 mL/min/1.73 m2 at the screening visit

  • Note: If an individual has an estimated GFR <30 mL/min/1.73 m2, 1 repeat test is allowed. The individual may be enrolled if repeat demonstrates estimated GFR of ≥30 mL/min/1.73 m2

• Documented history of liver cirrhosis or known liver disease with current evidence of ongoing impaired liver function (eg, screening INR >1.5 x ULN that is considered hepatic in origin)
• Has a screening serum ALT levels >1.5 x ULN and/or total bilirubin >2 x ULN (unless bilirubin elevation is due to suspected Gilbert’s syndrome and only involves elevation in indirect bilirubin) (One repeat serum ALT measurement and 1 repeat total bilirubin measurement are allowed before randomization)
• Known hypersensitivity to pozelimab, cemdisiran, or to any components of their respective formulations
• Has received a COVID-19 vaccination within 1 week of randomization
• Members of the clinical site study team and/or his/her immediate family, unless prior approval granted by the sponsor
• Pregnant or breastfeeding women

• WOCBP* who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 28 weeks after the last dose. Highly effective contraceptive measures include:

  •  stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral,injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening;

  • intrauterine device; intrauterine hormone-releasing system

  • bilateral tubal occlusion/ligation

  • vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure)

  • sexual abstinence

• Is committed to an institution by virtue of an order issued either by the judicial or the administrative authorities (Note: Only for sites in Germany)
• History or current use of any experimental treatment for AMD, with the exception of intravitreal complement inhibitors, which may be used up to 6 months prior to randomization in either eye. (Note: Over-the-counter vitamins, supplements, or diets are not exclusionary)
• Ongoing participation in any clinical research study evaluating an investigational new drug for any condition, or prior participation with the last dose being administered within 30 days or 5 half-lives prior to randomization, whichever is longer

Astellas 7317-CL-0003

A Phase 1b, Multicenter, Dose Escalation, Evaluation of Safety and Tolerability of ASP7317 for Geographic Atrophy Secondary to Age-related Macular Degeneration

Inclusion Criteria

General Inclusion Criteria

1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act [HIPAA] Authorization for US sites) must be obtained from the participant prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Participant is 50 years of age or older at the time of signing the informed consent form (ICF).
3. Participant must be willing to take tacrolimus and willing to discontinue any medications that have a known strong interaction with tacrolimus.
4. Participant is able and willing to undertake all scheduled visits and assessments up to the week 52 visit.
5. Participant who is taking an antidepressant must be on a stable and effective dosage and must be willing to take it reliably for as long as it is required.
6. Participant must be willing and medically suitable to undergo monitored anesthesia care during the vitrectomy and subretinal injection
7. Participant agrees to conform to local and institutional policies regarding active COVID-19 infections.
8. Participant agrees not to participate in another interventional study until the 52-week visit has been completed.
9. Female participant is not pregnant and at least one of the following conditions apply:
   • Not a woman of childbearing potential (WOCBP)
   • WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 52 weeks after investigational product (IP) administration.
10. Female participant must agree not to breastfeed starting at screening and throughout the study period and for 52 weeks after IP administration.
11. Female participant must not donate ova starting at first dose of IP and throughout the study period and for 52 weeks after IP administration.
12. Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception  throughout the treatment period and for 52 weeks after IP administration.
13. Male participant must not donate sperm during the treatment period and for 52 weeks after IP administration.
14. Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 52 weeks after IP administration.

Ocular Inclusion Criteria 

Study Eye (Both Groups)

1. Participant has bilateral GA secondary to AMD. GA is defined as sharply demarcated areas of loss of the RPE.
2. Participant has no known history of CNV (wet AMD) in either eye prior to enrollment in the trial and no evidence of prior or active CNV with optical coherence tomography-angiography (OCT-A) or indocyanine green angiography (ICG-A), as assessed by the reading center.
3. Participant has absence of exudation as assessed by fluorescein angiography (FA) and spectral domain-optical coherence tomography (SD-OCT).
4. Participant has presence of either banded or diffuse hyper autofluorescence in the junctional zone of GA as assessed by the central reading center.
5. Participant has sufficiently clear ocular media, adequate pupillary dilation, and fixation to permit quality fundus imaging.
6. Participant is pseudophakic.

Study Eye (Group 1 Only)

1. For Cohort 1, the participant has a BCVA between light perception and ≤ 23 ETDRS letters at the screening visit. For Cohorts 2 and 3, the participant has a BCVA score between 20 (≥ 20/400) and 37 (≤ 20/200) ETDRS letters at the screening visit.
2. Participant has the total GA area < 30.5 mm2 (< 12 disc areas [DA]).

Study Eye (Group 2 Only)

1. Participant has BCVA score between 38 (> 20/200) and 63 (≤ 20/63) ETDRS letters during the screening visit.
2. Participant has the total GA area of > 5.1 mm2 and < 17.8 mm2 (≥ 2 and ≤ 7 DA, respectively) and must reside completely within the FAF imaging field (Field 2 to 30 degree image centered on the fovea). If GA is multifocal, at least 1 focal lesion must be ≥ 2.5 mm2 (≥ 1 DA).
3. Participant has a difference in mean mesopic sensitivity ≤ 2 dB between 2 tests at screening. If not ≤ 2 dB, a third test may be conducted and mean values between the second and third assessments must be ≤ 2 dB.

Selection of the Study Eye

1. If the participant’s eligibility is confirmed and both eyes meet all ocular eligibility criteria, then the study eye will be the eye with the worst BCVA score at the screening visit; however, if the BCVA scores for the 2 eyes are within 10 letters (logMAR 0.2), then the eye with the larger GA will be selected as the study eye.

Exclusion Criteria

General Exclusions

1. Participant has a history of recurrent VZV infection or a clinical diagnosis of VZV infection within 4 weeks of the baseline visit or positive anti-VZV immunoglobulin M (IgM). Being positive for immunoglobulin G (IgG), indicative of a past infection (or vaccination), is not an exclusionary criterion.
2. Participant has a history of recurrent cytomegalovirus (CMV) infection or a clinical diagnosis of CMV infection within 4 weeks of the baseline visit or positive anti-CMV IgM. Being positive for IgG, indicative of a past infection, is not an exclusionary criterion
3. Participant has a positive tuberculosis (TB) test during the screening period by an interferon gamma release assay (e.g., QuantiFERON) within the 6 months prior to the screening. If a participant has tested negative for TB within the 6 months prior to the screening visit, retesting is not required unless clinically indicated
4. Participant has a history or suspected active infection of toxoplasmosis or presence of elevated immunoglobulin M (IgM) toxoplasmosis titer within 4 weeks of the baseline visit
5. Participant has an active infection (ocular or non-ocular) requiring the prolonged or chronic use of antimicrobial or anti-infective agents
6. Participant has a current malignancy or history of malignancy within the past 5 years*, except non-metastatic basal or squamous cell carcinoma or keratoacanthoma or Bowen’s disease or carcinoma-in-situ of the cervix that has been successfully treated
   • Participants with a history of malignancy that is cured or in remission > 5 years may be included if his/her treating physician (e.g., oncologist or hematologist) provides a written confirmation to support that the participant is fit to receive the study adjunct immunosuppressive medication
7. Participant has a history of a solid organ or bone marrow transplant
8. Participant has any condition that would prohibit the use of systemic immunosuppression with tacrolimus
9. Participant is receiving or has received any immunosuppressive therapy (IMT) (other than topical, inhaled or low-dose systemic corticosteroid use not exceeding 7.5 mg of prednisone daily [or equivalent]) within 6 weeks or 5 plasma half-lives, whichever is longer, prior to the administration of adjunct study medications
10. Participant has a history of myocardial infarction in previous 12 months and whose disease is either unstable and/or symptomatic (e.g., angina, dyspnea, etc.).

11. Participant has electrocardiogram (ECG) results that are clinically significant and could either jeopardize the safety of the participant, impact the participant’s ability to comply with study visit schedule or impact the validity of the study results. Participants with a mean Fridericia-corrected QT interval of > 430 ms (for males) and > 450 ms (for females) at screening must be cleared by a cardiologist prior to the baseline visit.

12. Participant has a study day diastolic blood pressure > 95 mmHg, at either the screening or baseline visit. Study day blood pressure is defined as the average of the second and third readings at a study visit. If the study day blood pressure exceeds the limits, 1 additional triplicate can be taken.
13. Participant has an estimated glomerular filtration rate (eGFR) of ≤ 45 mL/min, calculated by the chronic kidney disease epidemiology collaboration (CKD-EPI) equation
14. Participant has an alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma-glutamyl transferase (GGT) and total bilirubin (TBL) ≥ 2 times the upper limit of normal (ULN).
15. Participant has severe anemia (hemoglobin < 9 g/dL [male] or hemoglobin < 8 g/dL [female]), leucopenia (white blood cell count < 2500/mm3), thrombocytopenia (platelet count < 80000/mm3) or polycythemia (hematocrit > 54% [male] or hematocrit > 49% [female])
16. Participant has a hemoglobin A1c > 8.5%.
17. Participant has a clinically significant coagulopathy (i.e., activated partial thromboplastin time [aPTT] ≥ 1.5 times the ULN and/or prothrombin time adjusted for the international normalized ratio [PT-INR] ≥ 2.0).
18. Participant has serology results indicative of having syphilis, Lyme disease, human immunodeficiency virus infection or active infection with HAV, HBV, HCV, or VZV.
19. Participant has a history of familial adenomatous polyposis or inflammatory bowel disease (i.e., Crohn’s disease, ulcerative colitis).
20. Participant has a history of allergic reaction to mydriatics or fluorescein.
21. Participant has a history of gene therapy or cell transplant therapy, including ASP7316, in a prior clinical study.
22. Participant has participated in any studies of an investigational drug (excluding vitamins and minerals for AMD studies) within 12 weeks prior to the screening visit.
23. Participant has participated with the study eye in any trial of a now FDA-approved complement inhibitor and/or has received an FDA approved complement inhibitor injection in the study eye within 24 weeks of the screening visit. After a washout period of 24 or more weeks, participants previously treated with a complement inhibitor will be eligible for participation, but participants will not be allowed to resume receiving any approved or investigational complement inhibitor in the study eye until the completion of the 52-week follow up period of the A7317-CL-0003 trial. Use of an FDA-approved complement inhibitor in the fellow, non-study eye is allowable.
24. Participant is unwilling to discontinue or avoid any CYP3A4 inducers (e.g., rifampin, rifabutin, phenytoin, carbamazepine, phenobarbital, St John's Wort) or participant is unwilling to discontinue or avoid protease inhibitors (e.g., nelfinavir, telaprevir, boceprevir), direct Factor Xa inhibitors, direct thrombin inhibitors, verapamil, diltiazem or erythromycin while taking tacrolimus.
25. Participant has a positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, opiates, cocaine, phencyclidine and methadone), unless the drug is taken for a documented medical condition and under the supervision of a physician

Ocular Exclusions

Study Eye

1. Participant has macular degeneration due to causes other than AMD (e.g., Stargardt disease, cone rod dystrophy, toxic maculopathies, etc.)
2. Participant has developed CNV (wet AMD), also known as exudative AMD in either eye
3. Participant has foveal sparing as determined by the presence of potentially viable photoreceptors, as evidenced by presence of ellipsoid zone (EZ) ≤ 250 microns from the foveal center, based on reading center assessments at the screening visit.
4. Participant has a history of vitrectomy or submacular surgery, or any surgical intervention for AMD. Participants with a history of non-AMD-related surgical interventions (other than vitrectomy and submacular surgery) are potentially eligible if they meet all other inclusion/exclusion criteria
5. Participant has prior treatment with photodynamic therapy (e.g., Visudyne®), intraocular external-beam radiation therapy or transpupillary thermotherapy.
6. Participant has a history of previous laser photocoagulation for CNV, diabetic macular edema, retinal vein occlusion and proliferative diabetic retinopathy.
7. Participant has a history of intravitreal drug delivery (e.g., anti-VEGF drugs, intravitreal corticosteroid injection or device implantation) in either eye within 1 year prior to the screening visit for any condition other than AMD. Use of anti-VEGF injections at any point in time due to prior history of CNV (wet AMD) is not permitted as prior history of wet AMD is an exclusionary criterion. Note: A single intraoperative administration of a corticosteroid during cataract surgery for cystoid macular edema prophylaxis or a single administration of anti-angiogenic agent > 1 year prior to screening is permitted
8. Participant has an abnormality of vitreoretinal interface (e.g., tractional epiretinal membrane), which can interfere with measurement of macular thickness or with the potential for macular structural damage.
9. Participant has a history of cystoid macular edema, retinal vascular occlusion, central serous chorioretinopathy, macular hole or retinoschisis.
10. Participant has peripheral holes or other peripheral retinal lesions that are considered of rhegmatogenous potential (that is, with a risk of causing retinal detachment).
    • Note: A prior hole, tear or other retinal lesion of rhegmatogenous potential that was treated at least 3 months prior and no longer poses a risk is permitted, as is an atrophic hole that the investigator deems to be without rhegmatogenous potential

11. Participant has active or history of intraocular inflammation such as uveitis, chorioretinitis and optic neuropathy. (other than glaucoma).

12. Participant has presence of an ocular toxoplasmosis scar.
13. Participant has nevus of Ota (oculodermal melanocytosis), a pigmented choroidal lesion showing characteristics associated with high risk of malignancy (e.g., elevated lesion) or a choroidal nevus in the macula.
14. Participant has pathologic myopia defined as a spherical equivalent of > 8.00 diopters or axial length > 28 mm at the screening visit, or myopic macular degeneration or posterior staphyloma.
15. Participant has glaucoma with uncontrolled IOP (defined as IOP > 25 mmHg despite treatment with anti-glaucoma medication) or is using more than 2 agents to control IOP or a history of glaucoma-filtering surgery.
16. Participant has a history of corneal transplantation
17. Participant has monocular vision; no light perception in the fellow eye or anophthalmic in the fellow eye.
18. Participant has a contraindication to pupil dilation
19. Participant has any other ocular condition that can interfere with the assessment of imaging data by the investigator’s discretion

EyeBio LTD, EYE-RES-103

A Randomized, Double-masked, Multi-center, 3-Arm Pivotal Phase 2/3 Study to Evaluate the Efficacy and Safety of Intravitreal EYE103 Compared with Intravitreal ranibizumab (0.5mg) in Participants with Diabetic Macular Edema

General Inclusion Criteria:

1. Be willing and able to understand the study procedures and the risks involved and provide written informed consent before the first study-related activity.
2. Be male or female ≥18 years of age
3. If female, have a negative serum pregnancy test at screening and further negative urine tests immediately before each dose of study medication if the participant is a female of childbearing potential (including those with <2 years since the onset of menopause, amenorrhea for <1 year, or not surgically sterile); such participants must agree to use a highly effective method of contraception from screening up to and including 3 months after the last dose of study drug (see Appendix B). She must also agree not to donate oocytes from screening up to and including 3 months after the last dose of study drug.
4. If male, be surgically sterile for at least 12 weeks, or agree to use a highly effective method of contraception, such as a condom and a second highly effective method of contraception from screening up to and including 90 days after the last dose of study drug (see Appendix B). He must also agree not to donate sperm from the time of the first dose until 12 weeks after the last dose of study drug.
5. Have type 1 or type 2 diabetes mellitus and a HbA1c of ≤12% and should be under regular investigation by a trained specialist as per local standard of care prior to and during the trial.
6. Have a BCVA ETDRS letter score between 75 and 24, inclusive, in the study eye at screening and on day 1. In the event both eyes are eligible, the worse-seeing eye should be enrolled in the trial.
7. Have a decrease in vision in the study eye determined by the investigator to be primarily the result of DME.
8. For participants who are treatment naïve for DME, the diagnosis must have been made within 9 months of screening. For all treatment-experienced participants, the first treatment should have been no longer than 3 years prior to the screening visit. If the participant has received anti-VEGF therapy previously, the last treatment must have been ≥90 days prior to the screening visit. For patients treated previously with 8 mg aflibercept (EYLEA HD) or faricimab (VABYSMO), treatment must have been ≥120 days prior to the Screening visit.
9. Have a CST of ≥325 μm in the study eye on SD-OCT as determined by the IRC at screening.

General Exclusions

1. Be pregnant or breastfeeding
2. Have been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
3. Have had renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis or have renal failure anticipated to require hemodialysis or peritoneal dialysis at any time during the study.

4. Have uncontrolled blood pressure, defined as systolic ≥180 mmHg and/or diastolic ≥100 mmHg while a participant is at rest

   • If a participant’s initial reading exceeds these values, a second reading may be obtained later the same day or on another day during the screening period. If the participant’s blood pressure is controlled by antihypertensive medication, the participant should be taking the same medication continuously for at least 30 days prior to Day 1

5. Have history of stroke (cerebral vascular accident) or myocardial infarction within 180 days prior to Day 1.
6. Have any active malignancy.
7. Have any history of organ transplant.
8. Newly diagnosed or previously untreated diabetes mellitus and initiated oral or injectable anti-diabetic medication within 3 months prior to Day 1. (This does not impact any changes to a participant’s medication regimen that may be deemed necessary for optimal glycemic control over the course of the study.)
9. If treatment-experienced for DME have a history of any of the following treatments within the noted time windows:
   • Have had prior treatment with 8 mg aflibercept (EYLEA HD) or faricimab (VABYSMO) within 120 days prior to the Screening visit in the study eye
   • Have had an IVT with other anti-VEGF treatments (ranibizumab, bevacizumab, aflibercept [2 mg], brolucizumab, pegaptanib sodium) in the study eye within 90 days of the Screening visit
   • Had prior IVT investigational agents in either eye at any time
   • Had treatment with ocriplasmin (JETREA®) in the study eye at any time
   • Had previous use of ILUVIEN® at any time, of OZURDEX® IVT implants within 180 days of the Screening visit, or any other intraocular or periocular corticosteroids in the study eye within 90 days of the Screening visit
10. Are currently using drugs with known retinal toxicity (e.g., Hydroxychloroquine, pentosan polysulfate sodium, and amiodarone).
11. Have history of cataract surgery and/or minimally invasive glaucoma surgery in the study eye within 90 days of screening.
12. Have any treatment for complications of cataract surgery with steroids or yttrium-aluminum garnet (YAG) laser capsulotomy within 90 days of Screening.
13. Have had pan-retinal photocoagulation or focal/grid thermal laser photocoagulation in the study eye within 90 days of screening
14. Have tractional retinal detachment in the study eye
15. Have advanced or uncontrolled glaucoma (defined as IOP ≥25 mmHg despite treatment with antiglaucoma medication) in the study eye.
16. Have had glaucoma-filtering surgery (trabeculectomy or tube shunt) in the study eye.
17. Have any history of retinal detachment or treatment or surgery for retinal detachment in the study eye
18. Have any history of uveitis in either eye
19. Have significant media opacities, including cataract, in the study eye that might interfere with VA, assessment of safety, OCT, or fundus photography in the opinion of the reading center.
20. Have a cataract in the study eye that, in the judgment of the investigator is expected to require surgical extraction within 4 months of screening.
21. Have aphakia in the study eye
22. Have an allergy to fluorescein dye
23. Have had vitrectomy in the study eye
24. Have known or former (if the participant has undergone refractive and/or cataract surgery) refractive error with a spherical equivalent of ≥±8 diopters
25. Have active retinal disease other than the condition (DME/diabetic retinopathy) under investigation in the study eye
26. Have any history or evidence of a concurrent ocular condition present in the study eye that, in the opinion of the investigator, could require either medical or surgical intervention or affect macular edema or alter VA during the study (e.g., Vitreomacular traction, epiretinal membrane, choriodal neovascularization due to NVAMD or other causes, such as pathological myopia, angioid streaks, presumed ocular histoplasmosis syndrome, and multifocal choroiditis)
27. Have active or suspected ocular or periocular infection or inflammation in either eye at day 1
28. Currently have evidence of, or a history of any clinically significant autoimmune, cardiovascular, hematologic, hepatic, metabolic, peripheral vascular, renal, or respiratory disease, which, in the opinion of the investigator, would prevent the participant from completing the required assessments for this study
29. Have a known hypersensitivity to any of the components of EYE103 formulation or prior hypersensitivity to mAbs
30. Have previously participated in any study of EYE103
31. Presence of amblyopia, amaurosis or ocular disorders with BCVA <35 letters (ETDRS testing charts) in the fellow eye at screening. This includes conditions that are anticipated to be transient, such as vitreous hemorrhage.
32. Have macular edema in the study eye considered to be secondary to a cause other than DME (e.g., Retinal vein occlusion, Irvine-Gass syndrome).
33. Have active iris or angle neovascularization or neovascular glaucoma in the study eye.
34. Have active proliferative diabetic retinopathy (PDR) in the study eye (e.g., Any vitreous or preretinal hemorrhage, active neovascularization at optic disc [NVD], or active neovascularization elsewhere [NVE]) as determined by the IRC at screening.
35. Have structural damage to the center of the macula in the study eye that, in the opinion of the investigator or sponsor, is likely to preclude improvement in BCVA, including atrophy of the retinal pigment epithelium, subretinal fibrosis or scar, significant macular ischemia, organized hard exudates in the foveal center, or other evidence of chronic disruption of the macular architecture.

PEDIG ATS-23

A Randomized Trial of Dichoptic Treatment for Amblyopia in Children 4 to 7 Years of Age

Participant Inclusion Criteria

• Age 4 to 7 years
•  Visual acuity, measured in each eye without cycloplegia in current refractive correction (if applicable) using the ATS-HOTV VA protocol on a study-approved device displaying single surrounded optotypes, as follows:
  • VA in the amblyopic eye 20/40 to 20/200 inclusive
  • Age-normal VA in the fellow eye:
    • 4 years: 20/40 or better; 5-6 years: 20/32 or better; 7 years: 20/25 or better
  • Interocular difference ≥ 3 logMAR lines (i.e., amblyopic eye VA at least 3 logMAR lines worse than fellow eye VA)
• Amblyopia associated with strabismus, anisometropia, or both (previously treated or untreated)
  • Criteria for strabismic amblyopia: At least one of the following must be met:
    • Presence of a heterotropia on examination at distance or near fixation (with optical correction), must be <=5 prism diopters (∆) by SPCT at distance and near fixation
    • Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia)
  • Criteria for anisometropia: At least one of the following criteria must be met:
    • ≥1.00 D difference between eyes in spherical equivalent (SE)
    • ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes
  • Criteria for combined-mechanism: Both of the following criteria must be met:
    • A criterion for strabismus is met (see above)
    • ≥1.00 D difference between eyes in spherical equivalent OR ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes
• No more than 2 weeks (cumulative) of prior dichoptic treatment
•  No treatment with cycloplegic eyedrops (e.g., atropine) in the past 2 weeks; other treatments allowed up to enrollment but then must be discontinued.
•  Refractive correction is required (single vision lenses or contact lenses) for any of the following refractive errors based on a cycloplegic refraction completed within the last 7 months:
  
  • Hypermetropia of 2.50 D or more by SE
  • Myopia of amblyopic eye of 0.50D or more SE
  • Astigmatism of 1.00D or more
  • Anisometropia of more than 0.50D SE
• Spectacles/contact lens correction prescribing instructions referenced to the cycloplegic refraction completed within the last 7 months:
  • SE must be within 0.50D of fully correcting the anisometropia (if new glasses are prescribed, reduction in plus sphere must be symmetric in the two eyes).
  • SE must not be under corrected by more than 1.50D SE
  • Cylinder power in both eyes must be within 0.50D of fully correcting the astigmatism
  • Axis must be within +/- 10 degrees if cylinder power is ≤1.00D, and within +/- 5 degrees if cylinder power is >1.00D
  • Myopia must not be under corrected by more than 0.25D or over corrected by more than 0.50D SE, and any change must be symmetrical in the two eyes.
• Spectacles/contact lens correction (with or without other treatment such as patching) meeting the above criteria must be worn:
  • For at least 18 weeks (immediately prior to enrollment) OR until VA stability is documented (defined as <0.1 logMAR change by the same testing method measured on 2 consecutive exams at least 9 weeks apart)
    • For determining VA stability (non-improvement):
      • The first of two measurements may be made 1) in current correction, or 2) in trial frames with or without cycloplegia or 3) without correction (if new correction is prescribed)
      • The second measurement must be made without cycloplegia in the correct spectacles/contact lens correction that has been worn for at least 9 weeks.
      • NOTE: Because this determination is a pre-randomization, the method of measuring VA is not mandated.
•  Participant is willing to wear the Luminopia headset
•  Participant is willing to continue full-time spectacles/contact lens wear (if needed)
•  Participant is willing to accept assignment to either dichoptic shows (view 1 hour per day 6 days per week) OR part-time patching (2 hours per day 7 days per week) for 26 weeks.
• Interpupillary distance of 52mm to 72mm inclusive
• Investigator is willing to prescribe Luminopia or patching per protocol
• Parent understands the protocol and is willing to accept randomization
• Parent has phone (or access to phone) and is willing to be contacted by JAEB Center
• Relocation outside area of active PEDIG site within the next 52 weeks is not anticipated

Participant Exclusion Criteria

• Heterotropia more than 5∆ at distance or near (measured by SPCT in current correction)
• Prism lenses or need of a prism prescription at enrollment
• Current bifocal spectacles (eligible only if bifocal discontinued 2 weeks prior to enrollment)
• Myopia greater than -6.00D spherical equivalent in either eye
• Previous intraocular or refractive surgery
• Known skin reactions to patch or bandage adhesives
• Ocular co-morbidity that may reduce VA determined by an ocular examination performed within the past 7 months (Note: nystagmus per se does not exclude the participant if the above visual acuity criteria are met using patch occlusion. Fogging is not permitted)
• Diplopia more than once per week over the last week prior to enrollment by parental report
• History of light-induced seizures
• Severe developmental delay that would interfere with treatment or evaluation (in the opinion of the investigator). Participants with mild speech delay or reading and/or learning disabilities are not excluded.
• Immediate family member (biological or legal guardian, child, sibling, parent) of investigative site personnel directly affiliated with this study or an employee of the JAEB center for Health Research.

PEDIG / AST-24

A Randomized Trial of Dichoptic Treatment for Amblyopia in Children 8 to 12 Years of Age

Participant Inclusion Criteria

• Age 8 to <13 years
• VA, measured in each eye without cycloplegia in current refractive correction (if applicable) using the E-ETDRS VA protocol on a study-approved device displaying single surrounded optotypes, as follows:
  • VA in the amblyopic eye 20/40 to 20/200 inclusive (33 to 72 letters with E-ETDRS)
  • VA in the fellow eye 20/25 or better (≥ 78 letters with E-ETDRS)
  • Interocular difference ≥ 3 logMAR lines (≥ 15 letters) i.e., amblyopic eye VA at least 3 logMAR lines worse than fellow eye VA)
• Amblyopia associated with strabismus, anisometropia, or both (previously treated or untreated)
  • Criteria for strabismic amblyopia: At least one of the following must be met:
    • Presence of a heterotropia on examination at distance or near fixation (with optical correction), must be <=5 prism diopters (∆) by SPCT at distance and near fixation.
    • Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia)
  • Criteria for anisometropia: At least one of the following criteria must be met:
    • ≥1.00 D difference between eyes in spherical equivalent (SE)
    • ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes
  • Criteria for combined-mechanism: Both of the following criteria must be met:
    • A criterion for strabismus is met (see above)
    • ≥1.00 D difference between eyes in SE OR ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes
• No more than 2 weeks (cumulative) of prior dichoptic treatment
• No treatment with cycloplegic eyedrops (e.g., atropine) in the past 2 weeks; other treatments allowed up to enrollment but then must be discontinued
• Refractive correction is required (single vision lenses or contact lenses) for any of the following refractive errors based on a cycloplegic refraction completed within the last 7 months
  • Hypermetropia of 2.50 D or more by SE
  • Myopia of amblyopic eye of 0.50D or more SE
  • Astigmatism of 1.00D or more
  • Anisometropia of more than 0.50D SE
• Spectacles/contact lens correction prescribing instructions referenced to the cycloplegic refraction completed within the last 7 months:
  • SE must be within 0.50D of fully correcting the anisometropia (if new glasses are prescribed, reduction in plus sphere must be symmetric in the two eyes)
  • Hyperopia must not be under corrected by more than 1.50D SE or over corrected by more than 0.25D SE
  • Cylinder power in both eyes must be within 0.50D of fully correcting the astigmatism
  • Axis must be within +/- 10 degrees if cylinder power is ≤1.00D, and within +/- 5 degrees if cylinder power is >1.00D
  • Myopia must not be under corrected by more than 0.25D or over corrected by more than 0.50D SE, and any change must be symmetrical in the two eyes
• Spectacles/contact lens correction (with or without other treatment such as patching) meeting the above criteria must be worn:
  • For at least 18 weeks (immediately prior to enrollment) OR until VA stability is documented (defined as <1-line change by the same testing method measured on 2 consecutive exams at least 9 weeks apart)
    • For determining VA stability (non-improvement):
      • The first of two measurements may be made 1) in current correction, or 2) in trial frames with or without cycloplegia or 3) without correction (if new correction is prescribed)
      • The second measurement must be made without cycloplegia in the correct spectacles/contact lens correction that has been worn for at least 9 weeks.
      • NOTE: Because this determination is a pre-randomization, the method of measuring VA is not mandated
• Participant is willing to wear a headset
• Participant is willing to continue full-time spectacles/contact lens wear (if needed)
• Interpupillary distance of 52mm to 72mm inclusive
• Investigator is willing to prescribe continued spectacles/contact lens correction (if needed) or either dichoptic device per protocol
• Participant is willing to accept assignment to either continued spectacles/ contact lens wear alone, dichoptic movies/shows (view 1 hour per day 6 days per week) OR dichoptic games (play approximately 25 minutes per day, 6 days per week) for 19 weeks
• Parent understands the protocol and is willing to accept randomization.
• Parent has phone (or access to phone) and is willing to be contacted by JAEB Center staff.
• Relocation outside of area of an active PEDIG site for this study within the next 36 weeks is not anticipated

Participant Exclusion Criteria

• Heterotropia more than 5∆ at distance or near (measured by SPCT in current correction)
• Prism lenses or need of a prism prescription at enrollment
• Current bifocal spectacles (eligible only if bifocal discontinued 2 weeks prior to enrollment)
• Myopia greater than -6.00D spherical equivalent in either eye
• Ocular co-morbidity that may reduce VA determined by an ocular examination performed within the past 7 months (Note: nystagmus per se does not exclude the participant if the above visual acuity criteria are met using patch occlusion. Fogging is not permitted)
• Diplopia more than once per week over the last week prior to enrollment by parental report
•  History of light-induced seizures
• Previous intraocular or refractive surgery
• Strabismus surgery or Botox planned or within the past 6 months
• Severe developmental delay that would interfere with treatment or evaluation (in the opinion of the investigator). Participants with mild speech delay or reading and/or learning disabilities are not excluded
• Immediate family member (biological or legal guardian, child, sibling, parent) of investigative site personnel directly affiliated with this study or an employee of the JAEB center for Health Research

Protocol AM / DRCR

Randomized Trial Comparing Immediate versus Deferred Surgery for Symptomatic Epiretinal Membranes

• Age ≥50 years
• Vision better than 20/40
• Willing to wait for surgery
• No history of (DME), (RVO), or uveitis
• No retinal vascular disease, vitreous hemorrhage, retinal detachment, inflammatory disease, or associations other than vitreous syneresis, retinal break, or posterior vitreous detachment
• No known medical problems that will be a contraindication to surgery

COAST SLT study/ University of Pittsburg Collaborative study

A 48 month randomized clinical trial to compare the efficacy and safety of standard versus low energy primary SLT in eyes with OHT, mild-moderate POAG, and to determine the optimal interval and energy for repeat SLT (as needed at initially assigned energy versus annually at low energy)

Major Inclusions:

• Age 18 years or older
• Each eye with BCVA at least 20/200
• Both eyes with a qualifying diagnosis:
  • Ocular hypertension: IOP > 21 mmHg without glaucomatous optic neuropathy,
  • Early primary open-angle glaucoma: glaucomatous optic neuropathy, visual field mean deviation >-6.0 dB with no points in the central 5° 12 dB and no more than 1 central 5° point
  • Moderate primary open-angle glaucoma: glaucomatous optic neuropathy, visual field mean deviation -6.0 dB to >-12 dB and no more than 1 central 5° point

Major Exclusions:

• Severe POAG, pigmentary glaucoma, narrow angle glaucoma and all other types other than POAG.
• Mean IOP > 35 mmHg in either eye at the Eligibility or Baseline visit
• Contraindications to SLT, brimonidine, or any other study intervention
• Any intraocular surgical procedure within the past 6 months in either eye
• Pregnancy or planning to become pregnant in next four years