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    Summary
    EudraCT Number:2018-000457-53
    Sponsor's Protocol Code Number:STREAM
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2018-09-20
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2018-000457-53
    A.3Full title of the trial
    A phase 1/2, 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
    Etude de phase I/II en ouvert, visant à évaluer la sécurité, la tolérance et l’efficacité préliminaire de l’implantation dans un œil de cellules d’épithélium pigmentaire rétinien (EPR) dérivées de cellules souches humaines (CSh) chez des patients atteints de rétinite pigmentaire (RP) due à une mutation monogénique.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Tissue replacement therapy study in Retinitis Pigmentosa
    Etude de thérapie tissulaire dans la rétinite pigmentaire
    A.3.2Name or abbreviated title of the trial where available
    STREAM
    STREAM
    A.4.1Sponsor's protocol code numberSTREAM
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorCECS/I-STEM
    B.1.3.4CountryFrance
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportCECS/I-STEM
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGENETHON
    B.5.2Functional name of contact pointGéraldine HONNET
    B.5.3 Address:
    B.5.3.1Street Address1bis rue de l'internationale
    B.5.3.2Town/ cityEVRY
    B.5.3.3Post code91000
    B.5.3.4CountryFrance
    B.5.4Telephone number33169472964
    B.5.5Fax number33169471946
    B.5.6E-mailclinical_development@genethon.fr
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code ISTEM-01
    D.3.4Pharmaceutical form Implant
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPImplantation
    Subretinal use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Yes
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Retinitis Pigmentosa due to monogenic mutation
    Rétinite Pigmentaire due à une mutation monogénique
    E.1.1.1Medical condition in easily understood language
    Retinitis Pigmentosa
    Rétinite Pigmentaire
    E.1.1.2Therapeutic area Diseases [C] - Eye Diseases [C11]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10038914
    E.1.2Term Retinitis pigmentosa
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess safety and tolerability of implantation of the IMP (ISTEM-01) in patients with retinitis pigmentosa
    E.2.2Secondary objectives of the trial
    - 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
    E.2.3Trial contains a sub-study No
    E.3Principal 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
    E.4Principal 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
    E.5 End points
    E.5.1Primary 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
    E.5.1.1Timepoint(s) of evaluation of this end point
    from baseline to each visit,
    E.5.2Secondary 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
    E.5.2.1Timepoint(s) of evaluation of this end point
    see E.5.2
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Information not present in EudraCT
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months20
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 12
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others Yes
    F.3.3.7.1Details of other specific vulnerable populations
    Blind or visually impaired person
    F.4 Planned number of subjects to be included
    F.4.1In the member state12
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Long-term follow up can be proposed (amendment or new study to be submitted)
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-01-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-02-08
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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