Safety and Efficacy Study of OpRegen for Treatment of Advanced Dry-Form Age-Related Macular Degeneration

Study Overview
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Brief Summary
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The main objective of the study is evaluation of the safety and tolerability of OpRegen - Human embryonic stem cell-derived retinal pigment epithelial (RPE) cells. The study will also include initial exploration of the ability of transplanted OpRegen cells to engraft, survive, and moderate disease progression.

Detailed Description
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OpRegen® is a cell-based product composed of retinal pigment epithelial (RPE) cells, derived from human embryonic stem cells (hESC) and administered as a cell suspension either in ophthalmic Balanced Salt Solution Plus (BSS Plus) or in CryoStor® 5 (Thaw-and-Inject, TAI). This is a Phase I/IIa, dose-escalation, evaluating safety and tolerability of OpRegen transplantation to patients with progressive dry-AMD. The study includes also initial exploration of efficacy. A total of approximately 24 subjects will be enrolled. The subjects should be 50 years of age and older, with non-neovascular (dry) AMD, who have funduscopic findings of GA in the macula, with absence of additional concomitant ocular disorders. The subjects will be divided into four cohorts, according to their best corrected visual acuity (BCVA) and administered OpRegen dose.

Official Title
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Phase I/IIa Dose Escalation Safety and Efficacy Study of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium Cells Transplanted Subretinally in Patients With Advanced Dry-Form Age-Related Macular Degeneration (Geographic Atrophy)

Conditions
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Age-Related Macular Degeneration

Intervention / Treatment
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* Biological: OpRegen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 50 and older; Diagnosis of dry (non-neovascular) age related macular degeneration in both eyes; Funduscopic findings of dry AMD with progressive geographic atrophy in the macula; Best corrected central visual acuity equal or less than 20/200 in cohorts 1-3 and 20/64-20/250 in cohort 4 in the study eye by ETDRS vision testing; Vision in the non-operated eye must be better than or equal to that in the operated eye; Subjects with sufficiently good health to allow participation in all study-related procedures and complete the study follow up period (medical records); Ability to undergo a vitreoretinal surgical procedure under monitored anesthesia care; Blood counts, blood chemistry, coagulation and urinalysis without abnormal significance; Negative for TB (cohort 4), HIV, HBC, and HCV, negative for CMV IgM and EBV IgM; No history of malignancy (other than a non-melanoma skin cancer). For cancers in remission for more then 5 years enrollment is allowed with concurred documented approval of principal investigator and oncologist prior to enrollment; Willing to defer all future blood and tissue donation; Able to understand and willing to sign informed consent. Exclusion Criteria: Evidence of neovascular AMD by history, as well as by clinical exam, fluorescein angiography (FA), or ocular coherence tomography (OCT) at baseline in either eye; History or presence of diabetic retinopathy, vascular occlusions, uveitis, Coat's disease, glaucoma, cataract or media opacity preventing posterior pole visualization or any significant ocular disease other than AMD that has compromised or could compromise vision in the study eye and confound analysis of the primary outcome; History of retinal detachment repair in the study eye; Axial myopia greater than -6 diopters; At least 2 months following cataract removal in the study eye and Yttrium Aluminum Garnet (YAG) laser capsulotomy in the study eye in the past 4 weeks and any other ocular surgery in the study eye in the past 3 months prior to implantation; History of cognitive impairments or dementia; Contraindication for systemic immunosuppression; History of any condition other than AMD associated with choroidal neovascularization in the study eye (e.g. pathologic myopia or presumed ocular histoplasmosis); 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. Pregnancy or breastfeeding; Current participation in another clinical study. Past participation (within 6 months) in any clinical study of a drug administered systemically or to the eye. Currently receiving aspirin, aspirin containing products and/or any other coagulation modifying drugs which cannot be discontinued 7 days prior to surgery; History of cancer (other than a non-melanoma skin cancer). For cancers cured more than five years ago, enrollment is allowed with concurred documented approval of principal investigator and oncologist prior to enrollment.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OpRegen<br>Up to 12 legally blind subjects with best corrected visual acuity of 20/200 or less in first three cohorts and 12 subjects with best corrected visual acuity of 20/64 and 20/250 in fourth cohort | Biological: OpRegen<br>* Targeted dose of 50,000 - 200,000 cells will be delivered into the subretinal space.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment Emergent Adverse Events | An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. The AE's were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 3.0. | From study start till 12 months following last subject dosed, plus up to 90 days (up to approximately 6.5 years) | 
| Change From Baseline in Intraocular Pressure (IOP) |  | Baseline, Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Geographic Atrophy (GA) Lesion Area | The GA lesion area was based on available Fundus Autofluorescence (FAF) imaging data by a central reading center. | Baseline, Month 12 | 
| Change From Baseline in Visual Acuity | Change from baseline in visual acuity was measured by retro illuminated ETDRS chart from 4 meters distance. Visual acuity was reported as the number of letters read correctly. | Baseline, Month 12 | 
| Change From Baseline in National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) Quality of Life | The NEI VFQ-25 is a 25 item patient-reported questionnaire. The composite score ranges from 0-100 with the higher score indicating better visual function. | Baseline, Month 12 |