Research With Retinal Cells Derived From Stem Cells for Myopic Macular Degeneration
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|ClinicalTrials.gov Identifier: NCT02122159|
Recruitment Status : Withdrawn (Study to be revised. Future plans to be determined.)
First Posted : April 24, 2014
Last Update Posted : July 18, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Myopic Macular Degeneration||Biological: MA09-hRPE Cellular Therapy||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II, Open-Label, 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 Geographic Atrophy Secondary to Myopic Macular Degeneration|
|Study Start Date :||March 2013|
|Actual Primary Completion Date :||July 2016|
|Actual Study Completion Date :||July 2016|
Experimental: MA09-hRPE Cellular Therapy
MA09-hRPE cells for transplantation will be provided by Ocata Therapeutics as a suspension frozen to the temperature of liquid nitrogen (approximately -196 °C). They will be processed at UCLA under GMPs according to protocol. Following vitrectomy performed under general anesthesia or waking sedation at the surgeon's discretion, hRPE cells will be introduced into a subretinal bleb formed by the injection of balanced salt solution (BSS). Direct viewing will guide the implantation of thawed and washed MA09-hRPE cells, resuspended in BSS, into the created bleb over a period of one minute. To avoid cell reflux, the cannula used to introduce the cells will be held in position for an additional minute. 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.
Biological: MA09-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.
- 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
- Evidence of successful engraftment [ Time Frame: 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 [ Time Frame: 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02122159
|Principal Investigator:||Steven Schwartz, MD||University of California, Los Angeles|