Retinitis Pigmentosa due to monogenic mutation MedDRA version: 20.0 Level: PT Classification code 10038914 Term: Retinitis pigmentosa System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Code: ISTEM-01
Pharmaceutical Form: Implant
Sponsors
CECS/I-STEM
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Documented diagnosis of retinis 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: o Visual acuity = 20/200 in the best eye (legally blind) - For patient of the second cohort: o Visual acuity > 20/200 in the worst eye And o Visible photoreceptor outer nuclear layer (ONL) on a spectral domain optical coherence tomography (OCT) scan - For the two cohorts: o 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) o 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 o 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 - 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) - 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) - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess safety and tolerability of implantation of the IMP (ISTEM-01) in patients with retinitis pigmentosa ;Secondary Objective: - To evaluate the placement and position of the patch - To assess preliminary efficacy based on: o Evaluation of visual function o Eye fundus o Evaluation of photoreceptor survival ;Primary end point(s): Safety and tolerability measured by the incidence of adverse events (AE) or serious adverse events (SAE) evaluated by changes in ophthalmologic exams, laboratory parameters, vital signs and in the physical examination from baseline to each visit, will be evaluated for each patient and for the study as a whole ;Timepoint(s) of evaluation of this end point: from baseline to each visit, | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): All implanted patients: Evaluation of IMP placement and position. - Position of the therapeutic patch by serial biomicroscopic fundus photography evaluation at baseline and by study visit and by SLO autofluorescence at baseline and weeks 4, 8, 12, 24, 36 and 48 - Placement of the therapeutic patch by serial spectral domain Ocular Coherence Tomography (OCT) scan at baseline and by study visit - Change in leakage or perfusion in normal fundal vasculature and presence of abnormal vasculature by fundus fluorescein angiography at baseline and weeks 24 and 48 - Change in thickness of RPE layer by B-mode orbital ultrasound at weeks 4, 8, 16, 24, 36 and 48. For the second cohort only, preliminary efficacy based on: 1 - Visual function and eye assessment - Change in ETDRS/ best corrected visual acuity (BCVA) from baseline by study visit - Change in eye exam and IntraOcular Pressure (IOP) from baseline by study visit - Change in pupillometry and color vision from baseline, at weeks 4, 8, 12, 24, 36 and 48 - Change in central 30 degree of visual function (by Humphrey Field test) from baseline, at weeks 4, 8, 12, 24, 36 and 48 - Change in kinetic perimetry from baseline, at weeks 4, 8, 12, 24, 36 and 48 2 - Photoreceptor survival assessment: - Evidence of retinal and RPE functionnality by global, pattern and multifocal ERG at baseline and weeks 4, 8, 12, 24, 36 and 48 - Photoreceptor survival (indirect indication of RPE survival) by Adaptive Optics at baseline and at weeks 24 and 48 - Functional survival of retinal photoreceptors by microperimetry over hESC-derived RPE at weeks 4, 8, 12, 24, 36 and 48 ;Timepoint(s) of evaluation of this end point: see E.5.2 | — |
Countries
France
Contacts
Public ContactGéraldine HONNET
GENETHON
Outcome results
None listed