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 Advanced Dry AMD
Overview
- Phase
- Phase 1
- Intervention
- MA09-hRPE
- Conditions
- Dry Age Related Macular Degeneration
- Sponsor
- Astellas Institute for Regenerative Medicine
- Enrollment
- 13
- Locations
- 4
- Primary Endpoint
- Safety of hESC derived RPE cells
- 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 dry Age Related Macular Degeneration (AMD) and to perform exploratory evaluation of potential efficacy endpoints to be used in future studies retinal pigment epithelium (RPE) cellular therapy.
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 AMD patients- 50,000 MA09-hRPE cells transplanted Three AMD patients- 100,000 MA09-hRPE cells transplanted Four Better Vision AMD patients- 100,000 MA09-hRPE cells transplanted Three AMD patients- 150,000 MA09-hRPE cells transplanted Three AMD 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 55 years of age.
- •Patient should be in sufficiently good health to reasonably expect survival for at least four years after treatment
- •Clinical findings consistent with advanced dry AMD with evidence of one or more areas of \>250microns of geographic atrophy (as defined in the Age-Related eye Disease Study \[AREDS\] study) involving the central fovea.
- •GA defined as attenuation or loss of RPE as observed by biomicroscopy, OCT, and FA.
- •No evidence of current or prior choroidal neovascularization in the treated eye
- •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.
- •Electrophysiological findings consistent with advanced dry AMD.
- •Medically suitable to undergo vitrectomy and subretinal injection.
Exclusion Criteria
- •Presence of active or inactive CNV in the eye to be treated.
- •Presence or history of retinal dystrophy, retinitis pigmentosa, chorioretinitis, central serious choroidopathy, diabetic retinopathy or other retinal vascular or degenerative disease other than ARMD.
- •History of optic neuropathy.
- •Macular atrophy due to causes other than AMD.
- •Presence of glaucomatous optic neuropathy in the study eye, uncontrolled IOP, or use of two or more agents to control IOP (acetazolamide, beta blocker, alpha-1-agonist, antiprostaglandins, anhydrous carbonic inhibitors).
- •Cataract of sufficient severity likely to necessitate surgical extraction within 1 year.
- •History of retinal detachment repair in the study eye.
- •Axial myopia of greater than -8 diopters
- •Axial length greater than 28 mm.
- •History of malignancy (with the exception of successfully treated \[excised\] basal cell carcinoma\[skin cancer\] or successfully treated squamous cell carcinoma of the skin).
Arms & Interventions
MA09-hRPE
Experimental: Subretinal injection of MA09-hRPE * Cohort 1 50,000 cells * Cohort 2 100,000 cells * Cohort 2a Better Vision 100,000 cells * Cohort 3 150,000 cells * Cohort 4 200,000 cells
Intervention: MA09-hRPE
Outcomes
Primary Outcomes
Safety of hESC derived RPE cells
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
- exploratory evaluations for potential efficacy endpoints.(12 months)