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) - Full Text View

Sponsor:	Advanced Cell Technology
Information provided by (Responsible Party):	Advanced Cell Technology
ClinicalTrials.gov Identifier:	NCT01469832

Purpose

The purpose of this study is:

To evaluate the safety and tolerability of RPE cellular therapy in patients with SMD Group 3.

To evaluate potential efficacy endpoints to be used in future studies RPE cellular therapy.

Condition	Intervention	Phase
Stargardt's Macular Dystrophy Fundus Flavimaculatus Juvenile Macular Dystrophy	Biological: Biological: MA09-hRPE Cellular therapy	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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 (hESC-RPE) Cells in Patients With Stargardt's Macular Dystrophy (SMD)

Resource links provided by NLM:

Genetics Home Reference related topics: age-related macular degeneration X-linked juvenile retinoschisis

MedlinePlus related topics: Eye Diseases Macular Degeneration Retinal Disorders

U.S. FDA Resources

Further study details as provided by Advanced Cell Technology:

Primary Outcome Measures:

safety and tolerance of transplantation [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
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

Secondary Outcome Measures:

Evidence of successful engraftment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
•Evidence of successful engraftmentEvidence of successful engraftment will consist of:
- Structural evidence (OCT imaging, fluorescein angiography, autofluorescense photography, 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

Estimated Enrollment:	12
Study Start Date:	November 2011
Estimated Study Completion Date:	April 2014
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Patients will undergo subretinal injection of MA09-hRPE Cohort 1 50,000 cells Cohort 2 100,000 cells Cohort 3 150,000 cells Cohort 4 200,000 cells	Biological: Biological: MA09-hRPE Cellular therapy Cohort 1 50,000 cells Cohort 2 100,000 cells Cohort 3 150,000 cells Cohort 4 200,000 cells

Detailed Description:

This study is a Phase I/II, open-label, non randomized, sequential, multi-center clinical trial. There will be 3 cohorts, each consisting of 3 patients. The enrolled cohorts will be as follows:

Three SMD patients- 50,000 MA09-hRPE cells transplanted
Three SMD patients- 100,000 MA09-hRPE cells transplanted
Three SMD patients- 150,000 MA09-hRPE cells transplanted
Three SMD patients- 200,000 MA09-hRPE cells transplanted Patients will be enrolled sequentially, and within each cohort of 3 patients, each patient's clinical course over the first 6 weeks following cell transplantation will be reviewed by an independent (DSMB) before enrollment is opened for the next 2 patients. A full safety assessment of all 3 patients in each cohort will be made by the DSMB when the 3rd patient in each cohort completes 4 weeks of follow-up, and before the first patient in the next cohort receives a cell transplant.

Each cohort will be enrolled sequentially in turn.

The day of the cell implantation will be Day 0, and patients will remain in the study until the last visit at 12 months.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adult male or female over 18 years of age. Clinical diagnosis of SMD Group 3 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 that is not to receive the transplant will be no worse than 20/400 Electrophysiological findings consistent with SMD Group 3. 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.
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.

Exclusion Criteria:

History of malignancy. History of myocardial infarction in previous 12 months. History of diabetes mellitus. Any immunodeficiency. Any current immunosuppressive therapy other than intermittent or low dose cortico steroids.

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01469832

Locations

United Kingdom
Grampian University Hospitals NHS Trust, Foresterhill, Aberdeen Royal Infirmary Eye Unit	Recruiting
Aberdeen, United Kingdom
Contact: Vikki McBain 01224 552543
Principal Investigator: Noemi Lois
Moorefields Eye Hospital NHS Foundation Trust	Recruiting
London, United Kingdom, EC1V2PD
Contact: Heather Kneale 44(0) 207 608 4023 mol.therapy@ucl.ac.uk
Principal Investigator: James Bainbridge, MA MB BChir PhD FRCOpth

Sponsors and Collaborators

Advanced Cell Technology

Investigators

Principal Investigator:	James Bainbridge, MA MB BChir PhD FRCOpth	Moorefields Eye Hospital NHS Foundation Trust
Principal Investigator:	Noemi Lois, MD,PhD, FRCS	Aberdeen Royal Infirmary Eye Unit

More Information

No publications provided

Responsible Party:	Advanced Cell Technology
ClinicalTrials.gov Identifier:	NCT01469832 History of Changes
Other Study ID Numbers:	ACT hESC-RPE SMD 01 EU, 2011-000054-34
Study First Received:	November 8, 2011
Last Updated:	January 30, 2012
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Advanced Cell Technology:

Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
SMD

Additional relevant MeSH terms:

Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on May 23, 2012