CTRI/2024/04/065639 [Registered on: 15/04/2024] Trial Registered Prospectively
Last Modified On:
03/06/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug Biological Stem Cell Therapy
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
Study to Understand Safety Efficacy of Novel Stem Cell Formulation to Treat Late Stage Dry Age-related Macular Degeneration (d-AMD)
Scientific Title of Study
A Phase 1/2a Multi-Center Dose-Escalation Dose-Expansion Study to
Evaluate the Safety and Efficacy of Eyecyte-RPE™ when administered as a
Single-dose Subretinal Injection in Subjects with Geographic Atrophy
GA Secondary to Dry Age-related Macular Degeneration d-AMD
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Raja Narayanan
Designation
Director of Clinical Research
Affiliation
LV Prasad Eye Institute,
Address
Hyderabad Eye Research Foundation (HERF),
LV Prasad Eye Institute, Kallam Anji Reddy Campus, Banjara Hills, Hyderabad- 500034,
Telangana, India
Hyderabad TELANGANA 500034 India
Phone
9177111975
Fax
Email
narayanan@lvpei.org
Details of Contact Person Scientific Query
Name
Dr Rajani Battu
Designation
Co-founder and Chief Medical Officer
Affiliation
Eyestem Research Pvt. Ltd.
Address
Centre for Cellular and Molecular Platforms (C-CAMP)
NCBS-TIFR, GKVK Post, Bellary Road,
Bengaluru, Karnataka 560065 (INDIA)
Bangalore KARNATAKA 560065 India
Phone
9900265081
Fax
Email
rajani.battu@eyestem.com
Details of Contact Person Public Query
Name
Dr Jogin Desai
Designation
Founder and Chief Executive Officer
Affiliation
Eyestem Research Pvt. Ltd.
Address
Centre for Cellular and Molecular Platforms (C-CAMP)
NCBS-TIFR, GKVK Post, Bellary Road,
Bengaluru, Karnataka 560065 (INDIA)
Bangalore KARNATAKA 560065 India
Phone
9739383877
Fax
Email
jogin.desai@eyestem.com
Source of Monetary or Material Support
Eyestem Research Pvt. Ltd.
Centre for Cellular and Molecular Platforms (C-CAMP)
NCBS-TIFR, GKVK Post, Bellary Road,
Bengaluru, Karnataka 560065 (INDIA)
Primary Sponsor
Name
Eyestem Research Pvt. Ltd.
Address
Centre for Cellular and Molecular Platforms (C-CAMP)
NCBS-TIFR, GKVK Post, Bellary Road,
Bengaluru, Karnataka 560065 (INDIA)
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 3
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Rajpal
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences
Ansari
Nagar, New Delhi 110029 India
New Delhi DELHI
9818598899
vohrarajpal@gmail.com
Dr Raja Narayanan
LV Prasad Eye Institute
Hyderabad Eye Research Foundation (HERF),
LV Prasad Eye Institute, Kallam Anji Reddy Campus, Banjara Hills, Hyderabad- 500034,
Telangana, India Hyderabad TELANGANA
Institute Ethics Committee All India Institute of Medical Sciences
Approved
LV Prasad Eye Institute Ethics Committee
Approved
Shri Ganapati Netralaya Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: H353||Degeneration of macula and posterior pole,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Eyecyte-RPE™
Eyecyte-RPE™ is a suspension of hiPSCs (human induced Pluripotent Stem Cells)
derived Retinal Pigment Epithelial Cells.
Eyecyte-RPE™, developed by Eyestem can help to replace the damaged or lost RPE cells and potentially enable tissue regeneration in the diseased retina
Comparator Agent
NA
NA
Inclusion Criteria
Age From
50.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Men and women greater than or equal to 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.
a. 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.
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 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.
c. At least one of the lesions has to be sub-foveal.
ExclusionCriteria
Details
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 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 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.
23. Have participated as a subject in any clinical study within 6 months prior to the Screening visit.
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).
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
Primary Efficacy Endpoint
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
Outcome
TimePoints
Secondary Efficacy Endpoints
b. BCVA ETDRS
c. Fundus Photography
d. SD-OCT
e. Microperimetry
b. BCVA ETDRS
Screening (≥ 28 days),
Active Follow-up
Days- 1, 7, 14, 28, 42, 56, 70, 84,
120, 150 and 180
Safety Follow-up
Months- 12, 18, 24, 36, 48 and 60
c. Fundus Photography, d. SD-OCT and e. Microperimetry
Screening (≥ 28 days),
Active Follow-up
Days- 1, 7, 14, 28, 42, 56, 70, 84,
120, 150 and 180
Safety Follow-up
Months- 12, 18, 24, 36, 48 and
60
f. NEI VFQ-25 Quality of Life score
Screening (≥ 28 days),
Active Follow-up
Day 180
Safety Follow-up
Months- 12, 18, 24, 36, 48 and 60
Target Sample Size
Total Sample Size="54" Sample Size from India="54" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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-RPE™, 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-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 this that this therapy may have substantial therapeutic value in dry AMD.