Safety and Efficacy of Autologous Transplantation of iPSC-RPE in the Treatment of Macular Degeneration

Sponsor

Beijing Tongren Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05445063

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This project intends to perform autologous transplantation of induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE). The clinical-grade RPE will be transplanted into subretinal space to treat refractory age-related macular degeneration. The efficacy and safety of RPE transplants to treat macular degeneration will be monitored and analyzed with results from EDTRS, BCVA, OCT, ERG, microperimetry, and fluorescein angiography, before and after the treatment.

Condition or Disease	Intervention/Treatment	Phase
Macular Degeneration	Biological: Autologous iPSC-derived RPE	Phase 1

Detailed Description

The investigators will generate iPSC lines from recruited participants and differentiate the iPSC into RPE. Autologous iPSC-derived RPE will be transplanted into participants eyes by subretinal injections. The safety and efficacy will be closely monitored and analyzed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Safety and Efficacy of Autologous Transplantation of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in the Treatment of Macular Degeneration

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2026

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Participants receiving intervention Participants will receive autologous transplantation of induced pluripotent stem cell-derived retinal pigment epitheliums.	Biological: Autologous iPSC-derived RPE Autologous transplantation of iPSC-derived RPE

Arm

Intervention/Treatment

Experimental: Participants receiving intervention

Participants will receive autologous transplantation of induced pluripotent stem cell-derived retinal pigment epitheliums.

Biological: Autologous iPSC-derived RPE

Autologous transplantation of iPSC-derived RPE

Outcome Measures

Primary Outcome Measures

Safety measure [12 months]
Safety will be assessed by Adverse Events (AEs) of special interest in regards to the investigational product. This will include obtaining information about Serious Adverse Events (SAEs) that are neurologic, infectious, hematologic or fatal, any AE that causes the subject to withdraw from the study, any new diagnosis of an ocular or immune-mediated disorder, cancer (irrespective of prior history), ectopic or proliferative cell growth (RPE or non-RPE) with adverse clinical consequence, unexpected, clinically significant AE possibly related to the cell transplant procedure or the investigational product (autologous iPSC-RPE), pregnancy in a female subject or the partner of a male subject and pregnancy outcome.

Secondary Outcome Measures

Best Corrected Visual Acuity (BCVA) [12 months]
Change in visual acuity will be measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart.
Optical coherence tomography (OCT) imaging [12 months]
The number of patients with serious retinal detachment, retinal hemorrhage, and cystoid macular edema, and the change in target treatment areas.
Color and autofluorescence imaging [12 months]
Change in target treatment areas.
Fluorescein angiography [12 months]
Change in target treatment areas.
Fundus autofluorescence [12 months]
Change in target treatment areas.
Microperimetry [12 months]
Exploratory evaluations for the change of retinal sensitivity from baseline in the region of interest.
Electroretinography (ERG) [12 months]
Exploratory evaluations for the change of retinal electrophysiology responses from baseline.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged 50-75 years;
Clinical diagnosis is consistent with the definition of late dry AMD in the age-related eye disease study (AREDS), with one or more >250 um geographic atrophy in the fovea;
Clinical diagnosis is wet AMD, but no obvious efficacy after conventional treatment;
The BCVA of the target eye will be 0.05 to 0.3;
Voluntary as test subjects, informed consent, regular follow-up on time.

Exclusion Criteria:

One-eyed subjects;
Macular atrophy caused by other diseases in addition to AMD;
Suffer from retinitis pigmentosa, choroidal retinitis, central serous choroiditis, diabetic retinopathy, or other retinal vascular and degenerative diseases besides AMD;
Lens opacities (affecting the central vision), glaucoma, uveitis, retinal detachment, optic neuropathy, and other ocular histories;
Other intraocular surgery histories besides cataract surgery;
Combined with severe systemic diseases, such as heart failure, liver disease, renal insufficiency, cor pulmonale, COPD in the previous 12 months;
Combined with severe infectious diseases, such as HIV, HBV, HCV, syphilis, tuberculosis, etc;
Abnormal blood coagulation function or other laboratory tests;
If female and of childbearing potential, pregnant, breastfeeding, or planning to become pregnant through the study;
If male, refuse to use barrier and spermicide contraception during the study;
Malignant tumor and history of malignancy;
Any immune deficiency;
Allergy to tacrolimus or other macrolides;
Any immune deficiency;
Use glucocorticoids, immunosuppressive drugs, or antipsychotic drugs in the previous 3 months;
Use anticoagulant, or the platelet function is still not restored to normal after stopping antiplatelet drugs for 10 days;
A history of addiction to alcoholism or prohibited drugs;
Be participating in other intervention clinical trials or receiving other study medications;
Poor compliance, difficulty to complete the study, or refusal to informed consent;
Some other situations which might increase the risks of the subjects or interfere with clinical trials, such as mental disorders, cognitive dysfunction, etc.