Long Term Follow Up of Sub-retinal Transplantation of hESC Derived RPE Cells in Stargardt Macular Dystrophy Patients

• ClinicalTrials.gov Identifier: NCT02445612
• Recruitment Status: Completed
• First Posted: May 15, 2015
• Last Update Posted: November 13, 2020
• Sponsor: Astellas Institute for Regenerative Medicine
• Information provided by (Responsible Party): Astellas Pharma Inc ( Astellas Institute for Regenerative Medicine )

Study Description

Brief Summary:

The purpose of this study is to evaluate the long term safety and tolerability of MA09-hRPE cellular therapy in patients with advanced Stargardt's Macular Dystrophy (SMD) from one to five years following the surgical procedure to implant the MA09-hRPE cells.

Condition or disease	Intervention/treatment
Stargardt's Macular Dystrophy	Biological: MA09-hRPE

Detailed Description:

This study is a long term, follow up to the ACT MA09-hRPE 001 phase I/II trial, the phase I/II trial (referred to as the core protocol) was an open-label, non-randomized, dose escalation, multi-center trial. Thirteen SMD patients were treated in this trial. Ten patients with profound vision loss (visual acuity <=20/400) received a single subretinal injection of MA09-hRPE cells, starting at a dose of 50,000 MA09-hRPE cells (three patients), 100,000 MA09-hRPE cells transplanted (three patients), 150,000 MA09-hRPE cells transplanted (three patients) and increasing to a maximum dose of 200,000 MA09-hRPE cells transplanted (one patient). Three patients with severe to moderate vision loss (visual acuity <= 20/100) received a dose of 100,000 MA09-hRPE cells. All patients who participated in the core protocol are eligible for participation in this follow-up protocol.

The first visit of this long term follow-up protocol will correspond to the last visit of the core protocol, and will take place at 12 months post cell implantation. Informed consent will be obtained at this visit.

Patients will be evaluated at 18, 24, 36, 48 and 60 months post-transplant (or more frequently as clinically indicated). Follow-up will include obtaining information about ophthalmological findings and events of special interest as defined in the Primary Outcomes. At the last visit of this follow-up study, whether at 60 months post-transplant or at early discontinuation, patients will be invited to participate in a Safety Surveillance Study for an additional 10 years, under a separate protocol, which will continue to monitor the long term risks of MA09-hRPE cell transplantation.

Study Design

• Study Type: Observational
• Actual Enrollment: 13 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Long Term Follow Up to 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 Stargardt's Macular Dystrophy (SMD)
• Actual Study Start Date: July 11, 2012
• Actual Primary Completion Date: June 21, 2019
• Actual Study Completion Date: June 21, 2019

Groups and Cohorts

Group/Cohort	Intervention/treatment
Experimental: MA09-hRPE; Sub-retinal transplantation of MA09-hRPE cells	Biological: 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; Other Name: ASP7316

Outcome Measures

Primary Outcome Measures :

1. Safety assessed by Adverse Events (AEs) of special interest in regards to the investigational product [ Time Frame: 4 years ]
   This will include obtaining information about ophthalmological findings and Serious Adverse Events (SAEs) that are neurologic, infectious, hematologic or fatal, pregnancy in a female subject or the partner of a male subject and pregnancy outcome, any adverse event (AE) that causes a subject to withdraw from the study, any new diagnosis of an ocular or immune-mediated disorder, cancer, ectopic or proliferative cell growth (Retinal pigment epithelium (RPE) or non-RPE) with adverse clinical consequence, and unexpected, clinically significant AEs possibly related to the cell transplant procedure or the investigational product (MA09-hRPE cells).

Secondary Outcome Measures :

1. Incidence of graft failure or rejection [ Time Frame: 4 years ]
   Evidence of graft failure or rejection will consist of: Presence of retinal edema, cystoid macular edema, retinal white dots, retinal hemorrhage, serous retinal detachment, subretinal exudates, subretinal fibrosis, or vascular and/or optic disc leakage, elevated intraocular pressure or hypotony. Evidence of unanticipated and persistent or increasing non-infectious ocular inflammation (e.g., vasculitis, retinitis, choroiditis, vitritis, pars planitis, anterior segment inflammation/uveitis).
2. Number of patients with changes in ocular examinations or images [ Time Frame: 4 years ]
   The number of patients with clinically significant absolute values or changes from baseline in Intra-ocular pressure (IOP) and Best Corrected Visual Acuity (BCVA) will be summarized.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

The study population is by invitation only for previous participants in the core protocol.

Criteria

Inclusion Criteria:

• Must have been treated with hESC-RPE cell transplant in the core protocol.
• Able to understand and willing to sign the informed consent to participate in the follow-up study.

Exclusion Criteria:

• There are no exclusion criteria

Contacts and Locations

Locations

United States, California

Jules Stein Eye Institute, UCLA School of Medicine

Los Angeles, California, United States, 90095

United States, Florida

Bascom Palmer Eye Institute

Miami, Florida, United States, 33136

United States, Pennsylvania

Wills Eye Institute-Mid Atlantic Retina

Philadelphia, Pennsylvania, United States, 19107

Sponsors and Collaborators

Astellas Institute for Regenerative Medicine

Investigators

• Study Director: Medical Director; Astellas Institute for Regenerative Medicine

More Information

Additional Information:

Link to results on the Astellas Clinical Study Results website. 

Publications of Results:

Schwartz SD, Hubschman JP, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, Mickunas E, Gay R, Klimanskaya I, Lanza R. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet. 2012 Feb 25;379(9817):713-20. doi: 10.1016/S0140-6736(12)60028-2. Epub 2012 Jan 24.

Schwartz SD, Regillo CD, Lam BL, Eliott D, Rosenfeld PJ, Gregori NZ, Hubschman JP, Davis JL, Heilwell G, Spirn M, Maguire J, Gay R, Bateman J, Ostrick RM, Morris D, Vincent M, Anglade E, Del Priore LV, Lanza R. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet. 2015 Feb 7;385(9967):509-16. doi: 10.1016/S0140-6736(14)61376-3. Epub 2014 Oct 15.

• Responsible Party: Astellas Institute for Regenerative Medicine
• ClinicalTrials.gov Identifier: NCT02445612
• Other Study ID Numbers: 7316-CL-0004; ACT MA09-hRPE 001(SMD)LTFU ( Other Identifier: Sponsor )
• First Posted: May 15, 2015
• Last Update Posted: November 13, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

Keywords provided by Astellas Pharma Inc ( Astellas Institute for Regenerative Medicine ):

fundus flavimaculatus; ASP7316; SMD; long term follow-up; juvenile macular dystrophy

Additional relevant MeSH terms:

Macular Degeneration; Stargardt Disease; Retinal Degeneration; Retinal Diseases; Eye Diseases; Eye Diseases, Hereditary; Genetic Diseases, Inborn