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    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2016-002790-35
    Sponsor's Protocol Code Number:C12-48
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2018-01-17
    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 number2016-002790-35
    A.3Full title of the trial
    Phase I/II ex vivo gene therapy clinical trial for RDEB using autologous skin equivalent grafts genetically corrected with a
    COL7A1-encoding SIN retroviral vector
    A.3.2Name or abbreviated title of the trial where available
    EBGraft
    A.4.1Sponsor's protocol code numberC12-48
    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 SponsorINSERM
    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 supportEuropean commission (FP7)
    B.4.2CountryEuropean Union
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationINSERM
    B.5.2Functional name of contact pointSonia GUEGUEN
    B.5.3 Address:
    B.5.3.1Street Address8 rue de la Croix Jarry
    B.5.3.2Town/ cityPARIS
    B.5.3.3Post code75013
    B.5.3.4CountryFrance
    B.5.6E-mailrqrc.siege@inserm.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/09/630
    D.3 Description of the IMP
    D.3.1Product nameSIN RV-mediated COL7A1 corrected autologous skin equivalent
    D.3.4Pharmaceutical form
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPRoute of administration not applicable
    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 Yes
    D.3.11.3.3Tissue Engineered Product No
    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 Yes
    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
    The trial aims to treat the recessive dystrophic epidermolysis bullosa (RDEB) by grafting one to three subjects with RDEB with autologous COL7A1-modified skin equivalents, using SIN-RV encoding COL7A1 cDNA.
    E.1.1.1Medical condition in easily understood language
    The trial aims to treat the recessive dystrophic epidermolysis bullosa (RDEB) by grafting subjects with RDEB with autologous COL7A1-modified skin equivalents.
    E.1.1.2Therapeutic area Diseases [C] - Skin and Connective Tissue Diseases [C17]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10074980
    E.1.2Term Epidermolysis bullosa aquisita
    E.1.2System Organ Class 100000004858
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this phase I/II clinical trial is to evaluate the safety of grafting SIN RV-mediated COL7A1 gene-modified autologous SE in adults with RDEB.
    E.2.2Secondary objectives of the trial
    The secondary objectives are:
    1) To assess the efficacy of SIN RV-mediated COL7A1 gene-modified autologous SE in adults with RDEB at W2, M1, M3, M6 and M12 after grafting;
    2) To evaluate the immune response against the recombinant C7 at M1, M3, M6 and M12 after grafting;
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. ≥ 18 year-old
    2. Clinical and molecular diagnosis of RDEB with confirmed bi-allelic COL7A1 mutations
    3. Significantly reduced staining of C7 on skin biopsy, measured by immunofluorescence microscopy (IF)
    4. A reduced number of or morphologically abnormal anchoring fibrils confirmed by TEM
    5. Presence of non-collagenous-1 domain (NC-1) of C7 on skin biopsy, measured by immunofluorescence microscopy (IF) and/or Western blot analysis
    6. Presence of ≥100cm2 of blistered and/or erosive skin areas including chronic wounds suitable for skin grafting
    7. Ability to undergo anaesthesia for grafting procedures
    8. Subjects aged ≥ 18years, willing and able to give informed consent
    E.4Principal exclusion criteria
    1. Recipients of other investigational medicinal products within 6 months prior to enrolment into this study
    2. Past medical history of biopsy proven skin malignancy
    3. Immunotherapy including oral corticosteroids (Prednisolone >1mg/kg) for more than one week (intranasal and topical preparations are permitted) or chemotherapy within 60 days of enrolment into this study
    4. Known allergy to any of the constituents of the investigational medicinal product (IMP) including Penicillin
    5. Subjects with BOTH:
    • positive serum antibodies to C7 confirmed by ELISA and
    • positive IIF with binding to the base of salt split skin and/or
    • positive Western blot
    6. Positive results for HIV, Hepatitis BsAg, Hepatitis BcAb, Hepatitis C IgG, HTLV1&2 or Syphilis serology
    7. Clinically significant medical, psychological or laboratory abnormalities limiting the ability of the subject to travel to the trial site(s) and to undergo grafting and follow-up procedures, as determined by the Investigator
    8. Absence of adequate social support
    9. Subjects who are pregnant, breast-feeding or of child-bearing potential who are neither abstinent nor practicing an acceptable means of contraception when this is in line with the usual and preferred lifestyle of the subject, as determined by the Investigator, for the duration of the trial
    E.5 End points
    E.5.1Primary end point(s)
    Primary Endpoints: Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit over a 12 months follow-up period.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At each visit over a 12 months follow-up period.
    E.5.2Secondary end point(s)
    Molecular endpoints
    1) Skin biopsy analysis of grafted skin at M1, M3, M6 and M12 compared to baseline for:
    a) C7 protein expression by immunofluorescence microscopy (IF)
    b) Morphology of anchoring fibrils (AFs) at the dermal-epidermal junction (DEJ) by transmission electron microscopy (TEM)

    2) Serum analysis at M1, M6 and M12 compared to baseline for:
    a) Detection of anti-C7 antibodies by enzyme-linked immunosorbent assay (ELISA) (against the entire C7 molecule) indirect immunofluorescence (IIF) and/or Western blot (WB)
    b) Detection of T-cell responses to the full length C7 by enzyme-linked immunosorbent spot (ELISPOT) assay

    Clinical endpoints
    Clinical assessment at M1, M3, M6 and M12 compared to baseline for:
    a) The scar quality measured by the Vancouver Scar Scale (VSS)
    b) Changes in blister numbers over the grafted skin
    c) Changes in the clinical appearance of grafted skin through clinical photographs at each visit
    d) Changes in pruritus measured by the Leuven Itch Scale (LIS)
    e) Changes in Quality of Life Score measured by the QOLEB
    E.5.2.1Timepoint(s) of evaluation of this end point
    Molecular endpoints
    1) Skin biopsy analysis of grafted skin at M1, M3, M6 and M12
    2) Serum analysis at M1, M6 and M12

    Clinical endpoints
    Clinical assessment at M1, M3, M6 and M12
    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 Yes
    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 No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    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: 3
    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 No
    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 No
    F.4 Planned number of subjects to be included
    F.4.1In the member state3
    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)
    None
    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 Decision2018-07-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-02-07
    P. End of Trial
    P.End of Trial StatusOngoing
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