Safety & Efficacy of Eyecyte-RPE™ in Patients With Geographic Atrophy Secondary to Dry Age-related Macular Degeneration.

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

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.

Study Overview

• Status: Recruiting
• Conditions: Eye Diseases; Age-Related Macular Degeneration; Macular Degeneration; Geographic Atrophy; Retinal Disease
• Intervention / Treatment: Drug: Eyecyte-RPE™

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.

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Dr Jogin Desai, MBBS; Phone Number: +91 7676235515; Email: jogin.desai@eyestem.com
• Study Contact Backup: Name: Dr Rajani Battu, MBBS,MS,DNB,FRCS(Edin),PhD; Phone Number: +91 7676235515; Email: rajani.battu@eyestem.com

Study Locations

• India
  • Maharashtra
    • Jalna, Maharashtra, India, 431203
      • Recruiting
      • Shri Ganapati Netralaya
      • Contact: Dr.Rushikesh Arunrao, MBBS,DNB
  • New Delhi
    • Delhi, New Delhi, India, 110029
      • Recruiting
      • All India Institute of Medical Sciences
      • Contact: Dr.Rajpal, MBBS,MD
  • Telangana
    • Hyderabad, Telangana, India, 500034
      • Recruiting
      • L V Prasad Eye Institute
      • Contact: Dr.Raja Narayanan, MBBS,MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men and women ≥ 50 years of age at Screening.
2. 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.

   1. Phase 1 ≤ 20/200 and
   2. Phase 2a ≥ 20/64 (ETDRS letter score 60) in the study eye at Screening.
4. Vision in the unoperated eye must be better or equal to vision in the study eye.
5. Willing, committed, and able to return for ALL clinic visits and complete all study related procedures.
6. Be medically suitable to undergo anesthesia, vitrectomy and subretinal injection in the opinion of the Investigator.
7. Be medically suitable for immunosuppression therapy in accordance with the requirements of this protocol in the opinion of the Investigator.
8. 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 center's assessment of Fundus Autofluorescence (FAF) imaging at screening:

    1. Total GA area must be ≥ 1.25 and ≤ 17.5 mm2 (0.5 and 7 disk areas [DA] respectively)
    2. 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.
    3. At least one of the lesions has to be sub-foveal.

Exclusion Criteria:

1. Have evidence of neovascular AMD in either eye by clinical examination, fluorescein angiography or optical coherence tomography.
2. 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.
3. 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.
4. Axial myopia greater than -6 diopters or axial length more than 26 mm.
5. 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.
7. Have a history or evidence of vitreous hemorrhage in the study eye.
8. 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.
9. Have had a prior pars plana vitrectomy in the study eye.
10. Have a history of retinal detachment or treatment or surgery for retinal detachment in the study eye.
11. Have history of a macular hole in the study eye.
12. 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.
13. Have had a prior trabeculectomy or other filtration surgery in the study eye.
14. History of any form of glaucoma in the study eye.
15. Patients with ocular pathology, particularly that of retina (other than AMD).
16. Have active intraocular inflammation or a history or evidence of uveitis in either eye.
17. 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.
18. Have a history of scleromalacia in either eye.
19. Have had previous therapeutic radiation in the study eye.
20. Have a history of corneal transplant or corneal dystrophy.
21. 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.
22. Have a history of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding 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.
23. Have participated as a subject in any clinical study within 6 months prior to Day 0, Baseline.
24. 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.
25. Be a female who is pregnant, breastfeeding, or of childbearing potential, unwilling to practice adequate contraception throughout the study at Screening and Baseline.
26. Currently receiving aspirin, aspirin containing products and/or any other coagulation modifying drugs which cannot be discontinued 7 days prior to surgery.
27. Have any systemic condition that would qualify the subject as being immunocompromised (e.g., severely uncontrolled diabetes, cancer).
28. Patients with Optic Atrophy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1-Cohort 1; Subjects who are allocated to Dose Level 1-Cohort 1 will receive 100,000 cells of Eyecyte-RPE™	Drug: Eyecyte-RPE™; Eyecyte-RPE™ is a suspension of hiPSCs (human induced Pluripotent Stem Cells) derived Retinal Pigment Epithelial Cells; Other Names: Subretinal Injection; Oral Tacrolimus; Oral Mycophenolate Sodium
Experimental: Dose Level 2-Cohort 2; Subjects who are allocated to Dose Level 2-Cohort 2 will receive 200,000 cells of Eyecyte-RPE™	Drug: Eyecyte-RPE™; Eyecyte-RPE™ is a suspension of hiPSCs (human induced Pluripotent Stem Cells) derived Retinal Pigment Epithelial Cells; Other Names: Subretinal Injection; Oral Tacrolimus; Oral Mycophenolate Sodium
Experimental: Dose Level 3-Cohort 3; Subjects who are allocated to Dose Level 3-Cohort 3 will receive 300,000 cells of Eyecyte-RPE™	Drug: Eyecyte-RPE™; Eyecyte-RPE™ is a suspension of hiPSCs (human induced Pluripotent Stem Cells) derived Retinal Pigment Epithelial Cells; Other Names: Subretinal Injection; Oral Tacrolimus; Oral Mycophenolate Sodium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fundus Autofluorescence-	Overall change in the geographic atrophy (GA) lesion area of the study eye over time using Fundus Autofluorescence (FAF)	Upto 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Corrected Visual Acuity (BCVA)-Mean change from baseline in BCVA score in study eye and fellow eye.	Change from baseline over time in BCVA as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The BCVA score (in letter units) will be reported.	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	Overall change in the GA lesion area of the study eye over time using SD-OCT	Upto 12 months
Fundus Photography- Changes between study eye and fellow eye	Correlation assessment between quantitative metrics derived from Color fundus photography images	Upto 12 months
Microperimetry-Mean change from baseline in mean sensitivity	Change from initial assessment over time in retinal sensitivity, as assessed by Microperimetry (MP)	Upto 12 months
National Eye Institute-Visual Function Questionnaire Quality of Life score	Change over time in National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) Quality of Life (QoL) score	Upto 12 months

Collaborators and Investigators

• Sponsor: Eyestem Research Pvt. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: April 15, 2024
• First Submitted That Met QC Criteria: April 30, 2024
• First Posted (Actual): May 1, 2024

Study Record Updates

• Last Update Posted (Actual): September 24, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Stem cells; Age Related Macular Degeneration; Geographic Atrophy; Visual Impairment; Subretinal injection; Retinal Pigment Epithelial Cells
• Additional Relevant MeSH Terms: Retinal Degeneration; Pathological Conditions, Anatomical; Macular Degeneration; Retinal Diseases; Geographic Atrophy; Eye Diseases; Atrophy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid
• Other Study ID Numbers: ERPL-CTP-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No