Interventional Study of Implantation of hESC-derived RPE in Patients With RP Due to Monogenic Mutation

• ClinicalTrials.gov Identifier: NCT03963154
• Recruitment Status: Active, not recruiting
• First Posted: May 24, 2019
• Last Update Posted: January 12, 2023
• Sponsor: Centre d'Etude des Cellules Souches
• Information provided by (Responsible Party): Centre d'Etude des Cellules Souches

Study Description

Brief 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.

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:

Condition or disease	Intervention/treatment	Phase
Retinitis Pigmentosa	Biological: Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE)	Phase 1; Phase 2

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: Open-label study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: August 19, 2019
• Estimated Primary Completion Date: August 15, 2023
• Estimated Study Completion Date: December 15, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Implantation of a therapeutical patch; 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.	Biological: 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))

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. Position of therapeutic patch [ Time Frame: From baseline until Week 56 ]
   Position of the therapeutic patch by serial images assessment
2. Placement of the therapeutic patch [ Time Frame: From Baseline until Week 56 ]
   Placement of the therapeutic patch by serial spectral domain Ocular Coherence Tomography (OCT) scan at baseline and by study visit
3. Change in leakage or perfusion [ Time Frame: At baseline and weeks 24, 48, and 56 ]
   Change in leakage or perfusion in normal fundal vasculature and presence of abnormal vasculature by fundus fluorescein angiography
4. Change in thickness of RPE layer [ Time Frame: At weeks 4, 8, 16, 24, 36, 48 and 56 ]
   Change in thickness of RPE layer by B-mode orbital ultrasound

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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
• 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

Exclusion Criteria:

• - 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
• 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

Contacts and Locations

Locations

France

•Centre Hospitalier National d'Ophtalmologie (CHNO) des Quinze-Vingts

Paris, France, 75012

Sponsors and Collaborators

Centre d'Etude des Cellules Souches

Investigators

• Principal Investigator: Stéphane BERTIN, MD; Centre des 15-20

More Information

• Responsible Party: Centre d'Etude des Cellules Souches
• ClinicalTrials.gov Identifier: NCT03963154
• Other Study ID Numbers: STREAM
• First Posted: May 24, 2019
• Last Update Posted: January 12, 2023
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Retinitis; Retinitis Pigmentosa; Retinal Diseases; Eye Diseases; Eye Diseases, Hereditary; Retinal Dystrophies; Retinal Degeneration; Genetic Diseases, Inborn