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

NCT03963154 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: STREAM
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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:

Conditions

Retinitis Pigmentosa

Outcome Measures

Primary Outcomes (1)

• Safety assessment

  Safety and tolerability measured by the incidence of Adverse Events or Serious Adverse Events throughout the study

  From Baseline until Week 56

Secondary Outcomes (4)

• Position of therapeutic patch

  From baseline until Week 56

• Placement of the therapeutic patch

  From Baseline until Week 56

• Change in leakage or perfusion

  At baseline and weeks 24, 48, and 56

• Change in thickness of RPE layer

  At weeks 4, 8, 16, 24, 36, 48 and 56

Study Arms (1)

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.

Biological: Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (RPE)

Interventions

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))

Implantation of a therapeutical patch

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:
• /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

You may not qualify if:

• \- 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

Sponsors & Collaborators

• Centre d'Etude des Cellules Souches: lead

Study Sites (1)

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

Paris, 75012, France

Location

MeSH Terms

Conditions

Retinitis Pigmentosa

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Stéphane BERTIN, MD

  Centre des 15-20

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label study

Study Record Dates

• First Submitted: May 22, 2019
• First Posted: May 24, 2019
• Study Start: August 19, 2019
• Primary Completion: June 22, 2023
• Study Completion (Estimated): December 15, 2026
• Last Updated: November 28, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)