Retinitis PigmentosaPhase 1/2NCT03963154
Interventional Study of Implantation of hESC-derived RPE in Patients With RP Due to Monogenic Mutation
A Phase 1/2 study testing Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE) in people with Retinitis Pigmentosa, run by Centre d'Etude des Cellules Souches at 1 site in France.
Trial summary
Phase I/II open-label, safety, tolerability and preliminary efficacy study of implantation into one eye of hESC-derived RPE (Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE)) in patients with retinitis pigmentosa due to monogenic mutation. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Retinitis Pigmentosa
- What is being tested?
- Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteFrance
- Study dates
- 19 Aug 2019to 15 Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented diagnosis of retinitis pigmentosa based on a genetic test confirming the presence of a monogenic mutation that affects a gene involved in the visual signalling process specifically at the level of RPEs, namely RPE65 or LRAT, or MerTK
- 18 years old ≤ Age ≤ 65 years old
- For patient of the first cohort:
- Visual acuity ≤ 20/200 in the best eye (legally blind)
- For patient of the second cohort:
- 20/63 > Visual acuity > 20/200 in the worst eye And
Show all 13Show fewer
- Visible photoreceptor outer nuclear layer (ONL) on a spectral domain optical coherence tomography (OCT) scan
- For the two cohorts:
- Negative serum pregnancy test in women of childbearing potential (a woman who is two years post-menopausal confirmed by a physician or surgically sterile is not considered to be of childbearing potential)
- Female patients of childbearing potential (if sexually active), committed to use two methods of contraception starting from the enrollment, during Mycophenolate Mofetil (MMF) treatment and for 6 weeks after the last dose of MMF
- Sexually active men (including vasectomized men) committed to use condoms during from the first day of MMF treatment and for at least 90 days after cessation of treatment
- Signed informed consents by the patient or legal guardian(s). For patients unable to give consent, authorization to participate to the study will be collected close to their legally authorized representative
- Affiliated to or a beneficiary of a health care system
Who cannot join
- - Patient unable or unwilling to comply with the protocol requirements
- History of allergy or sensitivity to one of the products used during the study
- Patients with known serious allergies to the fluorescein
- Patients with a contraindication to general anesthesia
- Prior treatment with a gene or cell therapy product
- Patients with chronic hepatitis B or C, i.e. positive hepatitis B surface antigen or hepatitis C RNA viral load positive
Show all 16Show fewer
- Patients infected with Human immunodeficiency virus (HIV)
- Anti-HLA antibodies positive at screening
- Pregnancy or breastfeeding
- Presence of any ocular disease or ocular media opacity which in the opinion of the investigator precludes accurate evaluation
- Participation in another drug or device clinical study within last 6 months prior to baseline
- Patients known to be affected by pathologies for which the symptoms or associated treatments can alter the visual function and/or affect the retina
- Systemic corticosteroid therapy or other immunosuppressive / immunomodulating or anti-retroviral drugs within 2 months prior to baseline
- Patients with a contraindication to immunosuppressive/immunomodulating therapy (MMF) such as severe chronic renal impairment, severe digestive system disease, Lesch-Nyhan disease, Kelley-Seegmiller syndrome…
- Acute illness or infection within 4 weeks of the anticipated administration of study medication which may interfere with study assessments and immunosuppressive/immunomodulating therapy
- Any other condition or history that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful completion of the study
Trial locations and contacts
1 site in 1 country.
France1 site
•Centre Hospitalier National d'Ophtalmologie (CHNO) des Quinze-Vingts
Paris, 75012
About this study
Official title: STREAM: A Phase 1/2, Open-label, Safety, Tolerability and Preliminary Efficacy Study of Implantation Into One Eye of hESC-derived RPE in Patients With Retinitis Pigmentosa Due to Monogenic Mutation
Phase I/II open-label, safety, tolerability and preliminary efficacy study of implantation into one eye of hESC-derived RPE (Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE)) in patients with retinitis pigmentosa due to monogenic mutation.
Study non randomized single group assignment consisting in 2 sequential cohorts of patients:
- First cohort of 2 patients with very advanced loss of visual acuity (legally blind)
- Second cohort of 10 patients with less advanced loss of visual acuity:
Read the detailed description
Monocentric study (Hospital of 15-20 at Paris) of duration of 106 weeks.
At total,12 evaluable patients will be enrolled and assigned in 2 cohorts as described above in brief summary.
Expected follow-up for one patient is about 64 weeks including 8 weeks of screening and baseline period and 56 weeks of follow-up after implantation of hESC-derived RPE.
After 56 weeks of follow-up, patients will be enrolled in a long term follow-up study during 4 additional years.
The primary objective is to assess safety and tolerability of implantation of the Investigational Medecinal Product (ISTEM-01) in patients with retinitis pigmentosa.
Secondary objectives are:
- To evaluate the placement and position of the patch
- To assess preliminary efficacy based on:
- Evaluation of visual function
- Eye fundus
- Evaluation of photoreceptor survival
Assessment of visual function by Diagnosys-Full-field stimulus threshold (D-FST) is the only exploratory objective.
- Conditions
- Retinitis Pigmentosa
- Being tested
- Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE)
- Medical subject headings
- Retinitis Pigmentosa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE)Biological
Implantation into one eye of hESC-derived RPE (Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE))
| Study group | Role | What they receive |
|---|---|---|
| Implantation of a therapeutical patch | Experimental | All the patients will receive a single central subretinal implantation in one eye of a monolayer of Human Embryonic Stem Cells-derived Retinal Pigmented Epithelium (hESC-derived RPE). The implanted eye will be the one with the worst visual acuity. Receives: Biological: Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety assessment
Safety and tolerability measured by the incidence of Adverse Events or Serious Adverse Events throughout the study
Measured: From Baseline until Week 56
Secondary outcomes (4)
Position of therapeutic patch
Position of the therapeutic patch by serial images assessment
Measured: From baseline until Week 56
Placement of the therapeutic patch
Placement of the therapeutic patch by serial spectral domain Ocular Coherence Tomography (OCT) scan at baseline and by study visit
Measured: From Baseline until Week 56
Change in leakage or perfusion
Change in leakage or perfusion in normal fundal vasculature and presence of abnormal vasculature by fundus fluorescein angiography
Measured: At baseline and weeks 24, 48, and 56
Change in thickness of RPE layer
Change in thickness of RPE layer by B-mode orbital ultrasound
Measured: At weeks 4, 8, 16, 24, 36, 48 and 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2019
- Study start19 Aug 2019
- Primary completion22 Jun 2023
- Study completion15 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Retinitis PigmentosaStudies 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
- Sequential
- Model description
- Open-label study
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre d'Etude des Cellules Souches
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stéphane BERTIN, MD, Principal investigator, Centre des 15-20
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03963154
- Sponsor's protocol ID
- STREAM
- Status last verified
- Nov 2023
- First submitted
- 22 May 2019
- Last updated
- 28 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- STREAM: A Phase 1/2, Open-label, Safety, Tolerability and Preliminary Efficacy Study of Implantation Into One Eye of hESC-derived RPE in Patients With Retinitis Pigmentosa Due to Monogenic Mutation
- ClinicalTrials.gov ID
- NCT03963154
- Acronym / sponsor ID
- STREAM
- Conditions
- Retinitis Pigmentosa
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Centre d'Etude des Cellules SouchesUniversity, hospital or other
- Study start
- 19 Aug 2019 (actual)
- Primary completion
- 22 Jun 2023 (actual)
- Study completion
- 15 Dec 2026 (estimated)
- First posted
- 24 May 2019 (actual)
- 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.
Phase I/II open-label, safety, tolerability and preliminary efficacy study of implantation into one eye of hESC-derived RPE (Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE)) in patients with retinitis pigmentosa due to monogenic mutation.
Study non randomized single group assignment consisting in 2 sequential cohorts of patients:
- First cohort of 2 patients with very advanced loss of visual acuity (legally blind)
- Second cohort of 10 patients with less advanced loss of visual acuity:
Detailed description
Monocentric study (Hospital of 15-20 at Paris) of duration of 106 weeks.
At total,12 evaluable patients will be enrolled and assigned in 2 cohorts as described above in brief summary.
Expected follow-up for one patient is about 64 weeks including 8 weeks of screening and baseline period and 56 weeks of follow-up after implantation of hESC-derived RPE.
After 56 weeks of follow-up, patients will be enrolled in a long term follow-up study during 4 additional years.
The primary objective is to assess safety and tolerability of implantation of the Investigational Medecinal Product (ISTEM-01) in patients with retinitis pigmentosa.
Secondary objectives are:
- To evaluate the placement and position of the patch
- To assess preliminary efficacy based on:
- Evaluation of visual function
- Eye fundus
- Evaluation of photoreceptor survival
Assessment of visual function by Diagnosys-Full-field stimulus threshold (D-FST) is the only exploratory objective.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label study
| Arm | Type | Receives |
|---|---|---|
| Implantation of a therapeutical patch | Experimental | Biological: Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE)All the patients will receive a single central subretinal implantation in one eye of a monolayer of Human Embryonic Stem Cells-derived Retinal Pigmented Epithelium (hESC-derived RPE). The implanted eye will be the one with the worst visual acuity. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Documented diagnosis of retinitis pigmentosa based on a genetic test confirming the presence of a monogenic mutation that affects a gene involved in the visual signalling process specifically at the level of RPEs, namely RPE65 or LRAT, or MerTK
- 18 years old ≤ Age ≤ 65 years old
- Visual acuity ≤ 20/200 in the best eye (legally blind)
- 20/63 > Visual acuity > 20/200 in the worst eye And
- Visible photoreceptor outer nuclear layer (ONL) on a spectral domain optical coherence tomography (OCT) scan
Key exclusion criteria (16 listed)
- - Patient unable or unwilling to comply with the protocol requirements
- History of allergy or sensitivity to one of the products used during the study
- Patients with known serious allergies to the fluorescein
- Patients with a contraindication to general anesthesia
- Prior treatment with a gene or cell therapy product
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 |
|---|---|---|
| Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE)Implantation into one eye of hESC-derived RPE (Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE)) | Biological | Implantation of a therapeutical patch |
Primary outcome
Safety assessment
Time frame: From Baseline until Week 56
Safety and tolerability measured by the incidence of Adverse Events or Serious Adverse Events throughout the study
4 secondary outcomes
Position of therapeutic patch
Time frame: From baseline until Week 56
Placement of the therapeutic patch
Time frame: From Baseline until Week 56
Change in leakage or perfusion
Time frame: At baseline and weeks 24, 48, and 56
Change in thickness of RPE layer
Time frame: At weeks 4, 8, 16, 24, 36, 48 and 56
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2023.
- Individual participant dataSharing planned: No
Related trials for Retinitis Pigmentosa
RecruitingObservational study
Rod and Cone Mediated Function in Retinal Disease
Retinal Degeneration, Retinitis Pigmentosa
RecruitingObservational study
Cell Collection to Study Eye Diseases
Retinal Disease, AMD
Recruiting
Brain Stimulation Effects on Orientation and Mobility Skills in Adults With Vision Impairment
Retinitis Pigmentosa (RP), Rod Cone Dystrophy
RecruitingObservational study
Universal Rare Gene Study: A Registry and Natural History Study of Retinal Dystrophies Associated With Rare Disease-Causing Genetic Variants
Inherited Retinal Degeneration, Retinitis Pigmentosa
Active, not recruitingObservational study
Rate of Progression in EYS Related Retinal Degeneration
Retinitis Pigmentosa, Eye Diseases
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.
Stéphane BERTIN, MD principal investigator
Centre des 15-20
1 site 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 Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE) in people with Retinitis Pigmentosa, run by Centre d'Etude des Cellules Souches at 1 site in France.
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 16 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: under way, not looking for participants, as of the sponsor's last update on 28 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
This study is still under way. Results are not available in the source record yet.
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 assessment (time frame: From Baseline until Week 56). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Nov 2023.