Research With Retinal Cells Derived From Stem Cells for Myopic Macular Degeneration

NCT02122159 | Withdrawn Phase 1 DMC

• 1 other identifier: JSEI MA09-hRPE MMD
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Myopic Macular Degeneration

Keywords

safety; tolerability; RPE cellular therapy; MMD

Outcome Measures

Primary Outcomes (1)

• Safety of hESC-derived RPE cells

  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

  12 months

Secondary Outcomes (2)

• Evidence of successful engraftment

  12 months

• Evidence of rejection

  12 months

Study Arms (1)

MA09-hRPE Cellular Therapy

EXPERIMENTAL

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

Interventions

MA09-hRPE Cellular Therapy BIOLOGICAL

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.

MA09-hRPE Cellular Therapy

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Ocata Therapeutics: collaborator

Study Officials

• Steven Schwartz, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Retina Division

Study Record Dates

• First Submitted: April 1, 2014
• First Posted: April 24, 2014
• Study Start: March 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: July 18, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will not share