Safety and Tolerability of Sub-retinal Transplantation of Human Embryonic Stem Cell Derived Retinal Pigmented Epithelial (hESC-RPE) Cells in Patients With Stargardt's Macular Dystrophy (SMD)
The purpose of this study is:
To evaluate the safety and tolerability of RPE cellular therapy in patients with SMD .
To evaluate potential efficacy endpoints to be used in future studies RPE cellular therapy.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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 (hESC-RPE) Cells in Patients With Stargardt's Macular Dystrophy (SMD)|
- safety and tolerance of transplantation [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]The safety and tolerance of transplantation of hESC-derived 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, or have tumorigenic potential, Adverse Event and Serious Adverse Event assessment, Serial vital signs and Clinical laboratory tests Direct ophthalmological monitoring Monitoring of RPE cells acceptance/integrity/rejection Monitoring of local and systemic infection or tumorigenic cell transformation
- Evidence of successful engraftment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
•Evidence of successful engraftmentEvidence of successful engraftment will consist of:
- Structural evidence (OCT imaging, fluorescein angiography, autofluorescence photography, slit-lamp examination with fundus photography) that cells have been implanted in the correct location
- Electroretinographic evidence (mfERG) showing enhanced activity in the implant location
|Study Start Date:||November 2011|
|Study Completion Date:||September 2015|
|Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
Experimental: Subretinal injection of MA09-hRPE
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 Vision 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01469832
|Lothian Health Board Headquarters at Waverley Gate|
|Edinburgh, United Kingdom, EH1 3EG|
|Moorefields Eye Hospital NHS Foundation Trust|
|London, United Kingdom, EC1V2PD|
|Newcastle on Tyne NHS Foundation Trust|
|Newcastle upon Tyne, United Kingdom, NE7 7DN|
|Study Director:||Medical Director||Astellas Institute for Regenerative Medicine|