Safety and Tolerability of Sub-retinal Transplantation of Human Embryonic Stem Cell Derived Retinal Pigmented Epithelial (hESC-RPE) Cells in Patients With Stargardt's Macular Dystrophy (SMD)

NCT01469832 | Completed Phase 1 DMC

• 3 other identifiers: 7316-CL-00032011-000054-34ACT hESC-RPE SMD 01 EU
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is: To evaluate the safety and tolerability of RPE cellular therapy in patients with SMD . To evaluate potential efficacy endpoints to be used in future studies RPE cellular therapy.

Conditions

Stargardt's Macular Dystrophy

Keywords

fundus flavimaculatus; Retinal Diseases; Macular Degeneration; SMD; juvenile macular dystrophy

Outcome Measures

Primary Outcomes (1)

• safety and tolerance of transplantation

  The safety and tolerance of transplantation of hESC-derived 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, or have tumorigenic potential, Adverse Event and Serious Adverse Event assessment, Serial vital signs and Clinical laboratory tests Direct ophthalmological monitoring Monitoring of RPE cells acceptance/integrity/rejection Monitoring of local and systemic infection or tumorigenic cell transformation

  12 months

Secondary Outcomes (1)

• Evidence of successful engraftment

  12 months

Study Arms (1)

Subretinal injection of MA09-hRPE

EXPERIMENTAL

* 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

Biological: MA09-hRPE

Interventions

MA09-hRPE BIOLOGICAL

* 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

Subretinal injection of MA09-hRPE

Eligibility Criteria

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

You may qualify if:

• Adult male or female over 18 years of age. Clinical diagnosis of SMD If known, the patient"s genotype will be recorded in the medical history, if unknown, patient will allow for the submission of a sample for genotyping.
• Independently verified clinical findings consistent with SMD. 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 SMD . Medically suitable to undergo vitrectomy and subretinal injection. Medically suitable for general anaesthesia or waking sedation, if needed.
• Medically suitable for transplantation of an embryonic stem cell line:
• 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.
• Negative urine screen for drugs of abuse.
• Negative human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV) serologies.
• No history of malignancy, with the exception of successfully treated basal cell or 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 chest roentgenogram (CXR); normal CBC \& manual differential; negative urinalysis (U/A);normal thyroid exam and thyroid panel; if male, normal testicular examination; if over age 40, 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 if 50 years of age or older, negative mammogram.
• If female and of childbearing potential, willing to use an effective form of birth control during the study.
• If male, willing to use barrier and spermicide 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.

You may not qualify if:

• History of malignancy, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin.
• History of myocardial infarction in previous 12 months. History of diabetes mellitus. Any immunodeficiency. Any current immunosuppressive therapy other than intermittent or low dose corticosteroids.
• Serologic evidence of infection with Hepatitis B, Hepatitis C, or HIV. Current participation in any other clinical trial. Participation within previous 6 months in any clinical trial of a drug by ocular or systemic administration.
• Any other sight-threatening ocular disease. Any chronic ocular medications. Any history of retinal vascular disease (compromised blood-retinal barrier. Glaucoma. Uveitis or other intraocular inflammatory disease. Significant lens opacities or other media opacity. Ocular lens removal within previous 3 months

Sponsors & Collaborators

• Astellas Institute for Regenerative Medicine: lead

Study Sites (3)

Lothian Health Board Headquarters at Waverley Gate

Edinburgh, EH1 3EG, United Kingdom

Location

Moorefields Eye Hospital NHS Foundation Trust

London, EC1V2PD, United Kingdom

Location

Newcastle on Tyne NHS Foundation Trust

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 22281388 BACKGROUND

• 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.

  PMID: 25458728 BACKGROUND

• Mehat MS, Sundaram V, Ripamonti C, Robson AG, Smith AJ, Borooah S, Robinson M, Rosenthal AN, Innes W, Weleber RG, Lee RWJ, Crossland M, Rubin GS, Dhillon B, Steel DHW, Anglade E, Lanza RP, Ali RR, Michaelides M, Bainbridge JWB. Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration. Ophthalmology. 2018 Nov;125(11):1765-1775. doi: 10.1016/j.ophtha.2018.04.037. Epub 2018 Jun 5.

  PMID: 29884405 DERIVED

Related Links

• Link to results on the Astellas Clinical Study Results website.
• Related Info

MeSH Terms

Conditions

Stargardt Disease; Retinal Diseases; Macular Degeneration

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Degeneration; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Medical Director

  Astellas Institute for Regenerative Medicine

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2011
• First Posted: November 10, 2011
• Study Start: December 13, 2011
• Primary Completion: September 30, 2015
• Study Completion: September 30, 2015
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)