A Phase 1/2a Multi-Center, Dose-Escalation Study to Evaluate the Safety & Efficacy of Eyecyte-RPE™ When Administered as a Single-dose Subretinal Injection in Subjects With Geographic Atrophy Secondary to Dry Age-related Macular Degeneration
Overview
- Phase
- Phase 1
- Intervention
- Eyecyte-RPE™
- Conditions
- Retinal Disease
- Sponsor
- Eyestem Research Pvt. Ltd.
- Enrollment
- 54
- Locations
- 3
- Primary Endpoint
- Fundus Autofluorescence-
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
The goal of this clinical study is to evaluate the safety and efficacy of novel stem cell formulation in patients having Geographic Atrophy (GA) Secondary to Dry Age-related Macular Degeneration (d-AMD).
The main questions it aims to answer are:
- Safety and tolerability of the novel stem cell formulation
- Potential efficacy of the novel stem cell formulation
Participants will receive a single subretinal injection in their study eye and followed up for safety.
This is an India only study and the product is developed indigenously.
Detailed Description
Age-related Macular Degeneration (AMD) is a leading cause of vision impairment in the elderly and substantially affects the quality of life of an individual. Although the exact pathophysiological mechanisms behind the disease are multifactorial and complex, several genetic and environmental risk factors are associated with AMD, such as age, cigarette smoking, hypertension, abdominal obesity, dietary fat, and low physical activity. Geographic Atrophy (GA) is the late stage of dry AMD(d-AMD). GA is a slow but inexorably progressive disease that causes irreversible blindness over time. Several new non-invasive tools such as Fundus Autofluorescence (FAF), Optical Coherence Tomography (OCT), and OCT Angiography (OCT-A) are being used to enable early diagnosis and follow up in these patients. Despite these advances, there are currently no approved treatments for GA that can replace the damaged RPE, photoreceptors, or outer retinal layers. In recent years, stem cell replacement therapy is being evaluated as an alternative to treat d-AMD. In the pursuit to find a promising solution for d-AMD, which is an unmet medical need globally, Eyestem has been striving to develop a safe and effective stem-cell based therapy. Theoretically, human induced pluripotent stem cells(hiPSCs) derived Eyecyte-RPE™, developed by Eyestem can help replace the damaged or lost retinal pigment epithelial (RPE) cells and potentially enable tissue regeneration in the diseased retina. In addition, stem cells can perform multiple functions, such as immunoregulation, prevention of apoptosis in sensory neurons, and secretion of neurotrophic factors. The latest stem cell transplantation studies performed by other research groups has been able to demonstrate that this therapy has a promising approach to restore visual function in eyes with degenerative retinal diseases. The results of the pre-clinical safety and efficacy studies with Eyecyte-RPE™ have been very encouraging. It has been shown to provide significant beneficial effects on the degenerating retina in animals without any significant safety concerns, suggesting that this therapy may have substantial therapeutic value in d-AMD.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Men and women ≥ 50 years of age at Screening.
- •Diagnosis of Geographic Atrophy secondary to d-AMD
- •Have Best Corrected Visual Acuity (BCVA) equal to or less than 20/200 Snellen (ETDRS letter score ≤ 35) in the study eye at screening.
- •Phase 1 ≤ 20/200 and
- •Phase 2a ≥ 20/64 (ETDRS letter score 60) in the study eye at Screening.
- •Vision in the unoperated eye must be better or equal to vision in the study eye.
- •Willing, committed, and able to return for ALL clinic visits and complete all study related procedures.
- •Be medically suitable to undergo anesthesia, vitrectomy and subretinal injection in the opinion of the Investigator.
- •Be medically suitable for immunosuppression therapy in accordance with the requirements of this protocol in the opinion of the Investigator.
- •Able to read (or if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member) and understand, and willing to sign the informed consent form (ICF)
Exclusion Criteria
- •Have evidence of neovascular AMD in either eye by clinical examination, fluorescein angiography or optical coherence tomography.
- •Have GA secondary to a condition other than AMD such as Stargardt disease, cone rod dystrophy or toxic maculopathies like Chloroquine maculopathy in either eye.
- •Have any evidence of active or inactive choroidal neovascularization (CNV) due to other causes such as ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, uveitis, punctate inner choroidopathy, or multifocal choroiditis in the study eye.
- •Axial myopia greater than -6 diopters or axial length more than 26 mm.
- •Have a decrease in BCVA in the study eye due to causes other than GA (e.g., pigment abnormalities, dense sub foveal hard exudates, previous vitreoretinal surgery, retinal dystrophies, non-retinal conditions, visually significant cataract, macular ischemia, etc.).
- •Have the presence of retinal pigment epithelial tears or rips involving the macula in the study eye at screening.
- •Have a history or evidence of vitreous hemorrhage in the study eye.
- •Have a history or clinical evidence of severe diabetic retinopathy, diabetic macular edema, retinal vein occlusion or any other vascular disease affecting the retina in the study eye.
- •Have had a prior pars plana vitrectomy in the study eye.
- •Have a history of retinal detachment or treatment or surgery for retinal detachment in the study eye.
Arms & Interventions
Dose Level 3-Cohort 3
Subjects who are allocated to Dose Level 3-Cohort 3 will receive 300,000 cells of Eyecyte-RPE™
Intervention: Eyecyte-RPE™
Dose Level 1-Cohort 1
Subjects who are allocated to Dose Level 1-Cohort 1 will receive 100,000 cells of Eyecyte-RPE™
Intervention: Eyecyte-RPE™
Dose Level 2-Cohort 2
Subjects who are allocated to Dose Level 2-Cohort 2 will receive 200,000 cells of Eyecyte-RPE™
Intervention: Eyecyte-RPE™
Outcomes
Primary Outcomes
Fundus Autofluorescence-
Time Frame: Upto 12 months
Overall change in the geographic atrophy (GA) lesion area of the study eye over time using Fundus Autofluorescence (FAF)
Secondary Outcomes
- Best Corrected Visual Acuity (BCVA)-Mean change from baseline in BCVA score in study eye and fellow eye.(Upto 12 months)
- Microperimetry-Mean change from baseline in mean sensitivity(Upto 12 months)
- National Eye Institute-Visual Function Questionnaire Quality of Life score(Upto 12 months)
- Spectral-Domain Optical Coherence Tomography (SD-OCT)-Mean change from baseline in the Geographic Atrophy (GA) area in study eye and fellow eye(Upto 12 months)
- Fundus Photography- Changes between study eye and fellow eye(Upto 12 months)