Sub-retinal Transplantation of hESC Derived RPE(MA09-hRPE)Cells in Patients With Stargardt's Macular Dystrophy
Primary Purpose
Stargardt's Macular Dystrophy
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MA09-hRPE
Sponsored by
About this trial
This is an interventional other trial for Stargardt's Macular Dystrophy focused on measuring juvenile macular dystrophy, SMD, fundus flavimaculatus
Eligibility Criteria
Inclusion Criteria:
- Adult male or female over 18 years of age.
- Clinical diagnosis of advanced 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.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.
- Peripheral visual field constriction documented on standard kinetic visual field testing.
- Electrophysiological findings consistent with SMD.
- 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:
- 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), 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 & if over age 50 years, 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; 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 40 years of age or older, negative mammogram.
- If female and of childbearing potential, willing to use two effective forms 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,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.
- If female, pregnancy or lactation.
- Any other medical condition, which, in the Investigator's judgment, will interfere with the patient's ability to comply with the protocol, compromises patient safety, or interferes with the interpretation of the study results.
Sites / Locations
- Jules Stein Eye Institute, UCLA School of Medicine
- Bascom Palmer Eye institute
- Wills Eye Institute-Mid Atlantic Retina
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
MA09-hRPE
Arm Description
Patients will undergo subretinal injection of MA09-hRPE
Outcomes
Primary Outcome Measures
The safety and tolerance of transplantation of hESC-derived RPE cells MA09-hRPE
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
Safety Assessments
Adverse Event and Serious Adverse Event assessment
Clinical monitoring
Serial vital signs
Clinical laboratory tests
Directed ophthalmological monitoring
Monitoring of RPE cells acceptance/integrity/rejection
Monitoring of local and systemic infection
Monitoring of tumorigenic cell transformation
Secondary Outcome Measures
Evidence of successful engraftment
Evidence of successful engraftment will consist of:
Structural evidence (OCT imaging, fluorescein angiography, autofluorescence 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
Full Information
NCT ID
NCT01345006
First Posted
April 28, 2011
Last Updated
July 4, 2021
Sponsor
Astellas Institute for Regenerative Medicine
1. Study Identification
Unique Protocol Identification Number
NCT01345006
Brief Title
Sub-retinal Transplantation of hESC Derived RPE(MA09-hRPE)Cells in Patients With Stargardt's Macular Dystrophy
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 (MA09-hRPE) Cells in Patients With Stargardt's Macular Dystrophy (SMD)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
June 16, 2011 (Actual)
Primary Completion Date
August 10, 2015 (Actual)
Study Completion Date
August 10, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Institute for Regenerative Medicine
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a safety and tolerability trial to evaluate the effect of subretinal injection of human embryonic stem cell derived retinal pigment epithelium cells in patients with Stargardt's Macular Dystrophy (SMD).
Detailed Description
This study is a Phase I/II, open-label, non randomized, sequential, multi-center clinical trial. There will be 5 cohorts, the 4 low vision cohorts will contain 3 patients, the better vision cohort will contain 4 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
Four Better Vison 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. The exception is the better vision group where all patients may be enrolled once DSMB approval has been received.
Each cohort will be enrolled sequentially in turn, with the exception of the better vision cohort which may be enrolled in parallel with the other cohorts.
The day of the cell implantation will be Day 0, and patients will remain in the study until the last visit at 12 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stargardt's Macular Dystrophy
Keywords
juvenile macular dystrophy, SMD, fundus flavimaculatus
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MA09-hRPE
Arm Type
Experimental
Arm Description
Patients will undergo subretinal injection of MA09-hRPE
Intervention Type
Biological
Intervention Name(s)
MA09-hRPE
Intervention Description
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
Primary Outcome Measure Information:
Title
The safety and tolerance of transplantation of hESC-derived RPE cells MA09-hRPE
Description
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
Time Frame
12 months
Title
Safety Assessments
Description
Adverse Event and Serious Adverse Event assessment
Clinical monitoring
Serial vital signs
Clinical laboratory tests
Directed ophthalmological monitoring
Monitoring of RPE cells acceptance/integrity/rejection
Monitoring of local and systemic infection
Monitoring of tumorigenic cell transformation
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Evidence of successful engraftment
Description
Evidence of successful engraftment will consist of:
Structural evidence (OCT imaging, fluorescein angiography, autofluorescence 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
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult male or female over 18 years of age.
Clinical diagnosis of advanced 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.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.
Peripheral visual field constriction documented on standard kinetic visual field testing.
Electrophysiological findings consistent with SMD.
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:
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), 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 & if over age 50 years, 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; 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 40 years of age or older, negative mammogram.
If female and of childbearing potential, willing to use two effective forms 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,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.
If female, pregnancy or lactation.
Any other medical condition, which, in the Investigator's judgment, will interfere with the patient's ability to comply with the protocol, compromises patient safety, or interferes with the interpretation of the study results.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Astellas Institute for Regenerative Medicine
Official's Role
Study Director
Facility Information:
Facility Name
Jules Stein Eye Institute, UCLA School of Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Bascom Palmer Eye institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Wills Eye Institute-Mid Atlantic Retina
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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."
Citations:
PubMed Identifier
30194931
Citation
Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018 Dec;196:xxv-xxix. doi: 10.1016/j.ajo.2018.08.038. Epub 2018 Sep 5.
Results Reference
derived
PubMed Identifier
25458728
Citation
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.
Results Reference
derived
PubMed Identifier
22281388
Citation
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.
Results Reference
derived
Links:
URL
https://astellasclinicalstudyresults.com/patientStudySearch.aspx?RID=;;;7316-CL-0001
Description
Link to results on the Astellas Clinical Study Results website.
Learn more about this trial
Sub-retinal Transplantation of hESC Derived RPE(MA09-hRPE)Cells in Patients With Stargardt's Macular Dystrophy
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