Stargardt's Macular DystrophyPhase 1/2NCT01469832
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)
A Phase 1/2 study testing MA09-hRPE in people with Stargardt's Macular Dystrophy, run by Astellas Institute for Regenerative Medicine at 3 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stargardt's Macular Dystrophy
- What is being tested?
- MA09-hRPE
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 13 Dec 2011to 30 Sep 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Lothian Health Board Headquarters at Waverley Gate
Edinburgh, EH1 3EG
Moorefields Eye Hospital NHS Foundation Trust
London, EC1V2PD
Newcastle on Tyne NHS Foundation Trust
Newcastle upon Tyne, NE7 7DN
About this study
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)
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.
Read the 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 Vision 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.
- Conditions
- Stargardt's Macular Dystrophy
- Being tested
- MA09-hRPE
- Keywords
- fundus flavimaculatus, Retinal Diseases, Macular Degeneration, SMD, juvenile macular dystrophy
- Medical subject headings
- Stargardt Disease, Retinal Diseases, Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MA09-hRPEBiological
- 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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: MA09-hRPE |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months
Secondary outcomes (1)
Evidence of successful engraftment
•Evidence of successful engraftmentEvidence 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
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2011 (estimated)
- Study start13 Dec 2011
- Primary completion30 Sep 2015
- Study completion30 Sep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Stargardt's Macular DystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Institute for Regenerative Medicine
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Astellas Institute for Regenerative Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01469832
- Sponsor's protocol ID
- 7316-CL-0003
- Other IDs
- 2011-000054-34, ACT hESC-RPE SMD 01 EU
- Status last verified
- Oct 2024
- First submitted
- 8 Nov 2011
- Last updated
- 31 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Publications
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.
PubMed 22281388Schwartz 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.
PubMed 25458728Mehat 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.
PubMed 29884405
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01469832
- Acronym / sponsor ID
- 7316-CL-0003
- Conditions
- Stargardt's Macular Dystrophy
- Keywords
- fundus flavimaculatus, Retinal Diseases, Macular Degeneration, SMD, juvenile macular dystrophy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Astellas Institute for Regenerative MedicineIndustry (pharma, biotech, devices)
- Study start
- 13 Dec 2011 (actual)
- Primary completion
- 30 Sep 2015 (actual)
- Study completion
- 30 Sep 2015 (actual)
- First posted
- 10 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 Vision 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Subretinal injection of MA09-hRPE | Experimental | 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Biological | Subretinal injection of MA09-hRPE |
Primary outcome
safety and tolerance of transplantation
Time frame: 12 months
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
1 secondary outcome
Evidence of successful engraftment
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2024.
- Background: PubMed 22281388Schwartz 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.
- Background: PubMed 25458728Schwartz 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.
- Derived from this study: PubMed 29884405Mehat 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No. Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Astellas Institute for Regenerative Medicine
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MA09-hRPE in people with Stargardt's Macular Dystrophy, run by Astellas Institute for Regenerative Medicine at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety and tolerance of transplantation (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01469832, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2024.