Dry Age Related Macular Degeneration
Conditions
Keywords
Dry AMD, Geographic atrophy
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.
Interventions
BIOLOGICALMA09-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
Sponsors
Astellas Institute for Regenerative Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
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 20/400. The visual acuity of the eye in the better vision cohort to receive the transplant will be no better than 20/100. * 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. * Medically suitable for general anesthesia or waking sedation, if needed. * Medically suitable for transplantation of an embryonic stem cell line: Any laboratory value which falls slightly outside of the normal range will be reviewed by the Medical Monitor and Investigators to determine its clinical significance. If it is determined not to be clinically significant, the patient may be enrolled into the study. * Normal serum chemistry (sequential multi-channel analyzer 20 \[SMA-20\]) and hematology (complete blood count \[CBC\], prothrombin time \[PT\], and activated partial thromboplastin time \[aPTT\]) screening tests. (NOTE:With the exception of abnormalities specifically identified in the
Exclusion criteria
) * Negative urine screen for drugs of abuse. * Negative human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV) serologies. * No history of malignancy (with the exception of successfully treated (excised) basal cell carcinoma\[skin cancer\] or successfully treated squamous cell carcinoma of the skin). * Negative cancer screening within previous 6 months: * complete history & physical examination; * dermatological screening exam for malignant lesions; * negative fecal occult blood test & negative colonoscopy within previous 7 years; * negative chest roentgenogram (CXR); * normal CBC & manual differential; * negative urinalysis (U/A); * normal thyroid exam; * if male, normal testicular examination; digital rectal examination (DRE) and prostate specific antigen (PSA); * if female, normal pelvic examination with Papanicolaou smear; and * If female, normal clinical breast exam and, negative mammogram. * If female and of childbearing potential, willing to use two effective forms of birth control during the study. * If male, willing to use barrier and spermicidal contraception during the study. * Willing to defer all future blood, blood component or tissue donation. * Able to understand and willing to sign the informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of hESC derived RPE cells | 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
| Measure | Time frame | Description |
|---|---|---|
| exploratory evaluations for potential efficacy endpoints. | 12 months | Secondary endpoints will be evaluated as exploratory evaluations for potential efficacy endpoints. * Change in the mean of BCVA * Autofluorescence photography * Reading speed Evidence of successful engraftment will consist of: * Structural evidence (OCT imaging, fluorescein angiography, 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 |
Countries
United States
Outcome results
None listed