Myopic Macular Degeneration
Conditions
Keywords
safety, tolerability, RPE cellular therapy, MMD
Brief summary
Pathologic myopia is a major cause of legal blindness worldwide. In myopic macular degeneration (MMD), there is degeneration of the retinal pigment epithelial (RPE) layer, and associated photoreceptors, resulting in vision loss. There is currently no standard treatment for MMD. Transplantation of intact sheets of RPE and suspensions of isolated individual RPE cells as well as autologous translocation of RPE cells has been attempted as treatment for AMD. Human photoreceptors are comprised of two cell types-rods and cones. Both have a close relationship with the outermost retinal cells, the retinal pigmented epithelium (RPE). The RPE is located between the choroid and the photoreceptors. The RPE maintains photoreceptor function by recycling photopigments,delivering, metabolizing and storing vitamin A, phagocytosing rod photoreceptor outer segments, transporting iron and small molecules between retina and choroid, maintaining Bruch's membrane and absorbing stray light to allow better image resolution. In essence, the RPE layer is critical to the function and health of photoreceptors and the retina as a whole. Human PRE (hRPE) transplantation may be a viable option for treatment of degenerative diseases of the retina. MA09-hRPE cells are fully differentiated human RPE cells derived from embryonic stem cells. Transplanted hRPE cells prepared by Advanced Cell Technology have been studied in rodent models of macular degenerative disease. The data suggests that the subretinal injection of ACT's hRPE cell products rescues, or at least delays, loss of visual function in two animal models of retinal degenerative diseases. The main purpose of this study is to evaluate the safety and tolerability of MA09-hRPE cellular therapy in patients with Myopic Macular Degeneration (MMD). Another objective is to evaluate potential efficacy endpoints to be used in future studies of RPE cellular therapy.
Interventions
BIOLOGICALMA09-hRPE Cellular Therapy
A suspension of either 50,000 MA09-hRPE cells (first cohort), 100,000 MA09-hRPE cells (second cohort), 150,000 MA09-hRPE cells (third cohort) or 200,000 MA09-hRPE cells (fourth cohort) in 150 uL of BSS plus will be implanted over 1 minute in the space created.
Sponsors
Ocata Therapeutics
University of California, Los Angeles
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult male or female over 40 years of age. * Patient should be in sufficiently good health to reasonably expect survival for at least four years after treatment * Axial myopia of equal to or greater than -8 diopters and/or axial length equal to or greater than 28 mm * Clinical findings consistent with MMD 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 * The visual acuity of the eye to receive the transplant will be no better than 20/80. * The visual acuity of the eye that is NOT to receive the transplant will be no worse than 20/400. * The eye with the more advanced disease and worse vision will be the study eye. * Electrophysiological findings consistent with macula-involving geographic atrophy. * 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 |
|---|---|---|
| Evidence of successful engraftment | 12 months | 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 |
| Evidence of rejection | 12 months | Evidence of rejection will consist of: • Structural (imaging) evidence that implanted MA09-hRPE cells are no longer in the correct location or the presence of vascular leakage If enhanced electroretinographic activity is observed after the transplantation, subsequent electroretinographic evidence that activity has returned to pre-transplant conditions may be an indication of graft rejection |
Outcome results
None listed