Study to Understand Safety Efficacy of Novel Stem Cell Formulation to Treat Late Stage Dry Age-related Macular Degeneration (d-AMD)

Phase 1/2

Recruiting

• Conditions: Degeneration of macula and posterior pole,

• Registration Number: CTRI/2024/04/065639
• Lead Sponsor: Eyestem Research Pvt. Ltd.

Brief Summary

Age-related Macular Degeneration (AMD) is a leading cause of vision impairment in the elderly and substantially affects the quality of life of an individua. 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 d-AMD. GA is a slow but inexorably progressive disease that causes irreversible blindness over time. In recent years, several new non-invasive tools are being used to enable early diagnosis and follow up in patients with GA, such as Fundus Autofluorescence (FAF), Optical Coherence Tomography (OCT), and OCT Angiography (OCT-A). 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 AMD, which is an unmet medical need globally, Eyestem has been striving to develop a safe and efficacious stem-cell based therapy.

Theoretically, hiPSCs derived Eyecyte-RPEâ„¢, developed by Eyestem can help replace the damaged or lost 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-RPEâ„¢ 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 this that this therapy may have substantial therapeutic value in dry AMD.

Detailed Description

Not available

Study Timeline

• Last Update Posted: 2024-03-06
• Study Start: 2024-05-13

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

• Men and women greater than or equal to 50 years of age at Screening.
• Diagnosis of Geographic Atrophy secondary to d-AMD 3.
• 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 less than or equal to 20/200 and b.
• Phase 2a less than or equal to 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) 9.
• Willing to provide signed Informed Consent prior to any procedures being performed at visit 1, screening 10.
• Negative for HIV, HbsAg, HCV, TB 11.The GA lesion must meet the following criteria as determined by the central reading centers assessment of Fundus Autofluorescence FAF imaging at screening a.
• Total GA area must be greater than or equal to 1.25 and less than or equal to 17.5 mm2 (0.5 and 7 disk areas [DA] respectively) b.
• The entire GA lesion must be completely visualized on the macula centered image and must be able to be imaged in its entirety and not contiguous with any areas of peripapillary atrophy.
• At least one of the lesions has to be sub-foveal.

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.) 6.
• 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 surgery for retinal detachment in the study eye.
• Have history of a macular hole in the study eye.
• Have had any other ocular surgery (except cataract) within 2 months or Yttrium Aluminum Garnet (YAG) laser capsulotomy in the study eye in the past 4 weeks.
• Have had a prior trabeculectomy or other filtration surgery in the study eye.
• History of any form of glaucoma in the study eye.
• Patients with ocular pathology, particularly that of retina (other than AMD).
• Have active intraocular inflammation or a history or evidence of uveitis in either eye.
• Have active ocular or periocular infection in either eye, or a history of any ocular or periocular infection within the 2 weeks prior to Visit 1, Screening in either eye.
• Have a history of scleromalacia in either eye.
• Have had previous therapeutic radiation in the study eye.
• Have a history of corneal transplant or corneal dystrophy.
• Have any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the subject beyond what is to be expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety.
• Have a history of other diseases, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications.
• Have participated as a subject in any clinical study within 6 months prior to the Screening visit.
• Have a known serious allergy to fluorescein sodium for injection in angiography, Povidone Iodine or any of the other medications required for anesthesia or the subretinal injection procedure.
• Be a female who is pregnant, breastfeeding, or of childbearing potential, unwilling to practice adequate contraception throughout the study at Screening and Baseline.
• Currently receiving aspirin, aspirin containing products and/or any other coagulation modifying drugs which cannot be discontinued 7 days prior to surgery.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary Efficacy Endpoint	At Screening (≥ 28 days), | During Active Follow-up on the following visits | Days- 1, 7, 14, 28, 42, 56, 70, 84, | 120, 150 and 180 | During Safety Follow-up on the following visits | Months- 12, 18, 24, 36, 48 and 60
a Fundus Autofluorescence	At Screening (≥ 28 days), | During Active Follow-up on the following visits | Days- 1, 7, 14, 28, 42, 56, 70, 84, | 120, 150 and 180 | During Safety Follow-up on the following visits | Months- 12, 18, 24, 36, 48 and 60

Secondary Outcome Measures

Name	Time	Method
Secondary Efficacy Endpoints	b. BCVA ETDRS
f. NEI VFQ-25 Quality of Life score	Screening (≥ 28 days),

Trial Locations

Locations (3)

Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences; 🇮🇳 Delhi, DELHI, India

LV Prasad Eye Institute; 🇮🇳 Hyderabad, TELANGANA, India

Shri Ganapati Netralaya; 🇮🇳 Jalna, MAHARASHTRA, India

Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences

🇮🇳Delhi, DELHI, India

Dr Rajpal

Principal investigator

9818598899

vohrarajpal@gmail.com