A Phase I/II, Open-Label, Multi-Center, Prospective Study to Determine the Safety and Tolerability of Sub-retinal Transplantation of Human Embryonic Stem Cell Derived Retinal Pigmented Epithelial (MA09-hRPE) Cells in Patients With Stargardt's Macular Dystrophy (SMD)
Overview
- Phase
- Phase 1
- Intervention
- MA09-hRPE
- Conditions
- Stargardt's Macular Dystrophy
- Sponsor
- Astellas Institute for Regenerative Medicine
- Enrollment
- 13
- Locations
- 3
- Primary Endpoint
- Safety Assessments
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a safety and tolerability trial to evaluate the effect of subretinal injection of human embryonic stem cell derived retinal pigment epithelium cells in patients with Stargardt's Macular Dystrophy (SMD).
Detailed Description
This study is a Phase I/II, open-label, non randomized, sequential, multi-center clinical trial. There will be 5 cohorts, the 4 low vision cohorts will contain 3 patients, the better vision cohort will contain 4 patients. The enrolled cohorts will be as follows: Three SMD patients- 50,000 MA09-hRPE cells transplanted Three SMD patients- 100,000 MA09-hRPE cells transplanted Four Better Vison SMD patients- 100,000 MA09-hRPE cells transplanted Three SMD patients- 150,000 MA09-hRPE cells transplanted Three SMD patients- 200,000 MA09-hRPE cells transplanted Patients will be enrolled sequentially, and within each cohort of 3 patients, each patient's clinical course over the first 6 weeks following cell transplantation will be reviewed by an independent (DSMB) before enrollment is opened for the next 2 patients. A full safety assessment of all 3 patients in each cohort will be made by the DSMB when the 3rd patient in each cohort completes 4 weeks of follow-up, and before the first patient in the next cohort receives a cell transplant. The exception is the better vision group where all patients may be enrolled once DSMB approval has been received. Each cohort will be enrolled sequentially in turn, with the exception of the better vision cohort which may be enrolled in parallel with the other cohorts. The day of the cell implantation will be Day 0, and patients will remain in the study until the last visit at 12 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adult male or female over 18 years of age.
- •Clinical diagnosis of advanced SMD.
- •If known, the patient's genotype will be recorded in the medical history, if unknown, patient will allow for the submission of a sample for genotyping.Clinical findings consistent with SMD.
- •The visual acuity of the eye to receive the transplant will be no better than 20/
- •The visual acuity of the eye in the better vision cohort to receive the transplant will be no better than 20/
- •The visual acuity of the eye that is not to receive the transplant will be no better than 20/400 for the worse vision patients and no worse than 20/100 for the better vision patients.
- •Peripheral visual field constriction documented on standard kinetic visual field testing.
- •Electrophysiological findings consistent with SMD.
- •Medically suitable to undergo vitrectomy and subretinal injection.
- •Medically suitable for general anesthesia or waking sedation, if needed.
Exclusion Criteria
- •History of malignancy,with the exception of successfully treated basal cell or squamous cell carcinoma of the skin.
- •History of myocardial infarction in previous 12 months.
- •History of diabetes mellitus.
- •Any immunodeficiency.
- •Any current immunosuppressive therapy other than intermittent or low dose corticosteroids.
- •Serologic evidence of infection with Hepatitis B, Hepatitis C, or HIV.
- •Current participation in any other clinical trial.
- •Participation within previous 6 months in any clinical trial of a drug by ocular or systemic administration.
- •Any other sight-threatening ocular disease.
- •Any chronic ocular medications.
Arms & Interventions
MA09-hRPE
Patients will undergo subretinal injection of MA09-hRPE
Intervention: MA09-hRPE
Outcomes
Primary Outcomes
Safety Assessments
Time Frame: 12 months
* Adverse Event and Serious Adverse Event assessment * Clinical monitoring * Serial vital signs * Clinical laboratory tests * Directed ophthalmological monitoring * Monitoring of RPE cells acceptance/integrity/rejection * Monitoring of local and systemic infection * Monitoring of tumorigenic cell transformation
The safety and tolerance of transplantation of hESC-derived RPE cells MA09-hRPE
Time Frame: 12 months
The transplantation of hESC-derived RPE cells MA09-hRPE will be considered safe and tolerated in the absence of: * Any grade 2 (NCI grading system) or greater adverse event related to the cell product * Any evidence that the cells are contaminated with an infectious agent * Any evidence that the cells show tumorigenic potential
Secondary Outcomes
- Evidence of successful engraftment(12 months)