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    Summary
    EudraCT Number:2016-002109-20
    Sponsor's Protocol Code Number:AAV2-hRPE65v2-301
    Clinical Trial Type:Outside EU/EEA
    Date on which this record was first entered in the EudraCT database:2016-10-24
    Trial results View 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
    H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED
    Expand All   Collapse All
    A. Protocol Information
    A.2EudraCT number2016-002109-20
    A.3Full title of the trial
    A Safety and Efficacy Study in Subjects with Leber Congenital Amaurosis (LCA) Using Adeno-Associated Viral Vector to Deliver the Gene for Human RPE65 to the Retinal Pigment Epithelium (RPE) [AAV2-hRPE65v2-301]
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Safety and Efficacy Study of Gene Therapy for RPE65-mediated Inherited Retinal Disease
    A.3.2Name or abbreviated title of the trial where available
    Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
    A.4.1Sponsor's protocol code numberAAV2-hRPE65v2-301
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT00999609
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/221/2015
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorSpark Therapeutics, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportSpark Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSpark Therapeutics, Inc.
    B.5.2Functional name of contact pointJennifer Wellman
    B.5.3 Address:
    B.5.3.1Street Address3737 Market St Suite 1300
    B.5.3.2Town/ cityPhiladelphia, PA
    B.5.3.3Post code19104
    B.5.3.4CountryUnited States
    B.5.4Telephone number001855772-7589
    B.5.5Fax number001215689-3760
    B.5.6E-mailclinicaltrials@sparktx.com
    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/3/12/981; EU/3/15/1518
    D.3 Description of the IMP
    D.3.1Product nameAdeno-associated viral vector serotype 2 carrying human RPE65 cDNA
    D.3.2Product code AAV2-hRPE65v2
    D.3.4Pharmaceutical form Concentrate and solvent for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntraocular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNVoretigene neparvovec
    D.3.9.2Current sponsor codeAAV2-hRPE65v2
    D.3.9.3Other descriptive nameVORETIGENE NEPARVOVEC
    D.3.9.4EV Substance CodeSUB182301
    D.3.10 Strength
    D.3.10.1Concentration unit billion organisms/ml billion organisms/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5000
    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) No
    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 Yes
    D.3.11.3.5.1CAT classification and reference numberGene therapy medicinal product; Ref.: EMA/CAT/38194/2016.
    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
    Leber Congenital Amaurosis (LCA)
    E.1.1.1Medical condition in easily understood language
    Inherited Retinal Disease due to RPE65 mutations
    E.1.1.2Therapeutic area Diseases [C] - Eye Diseases [C11]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level PT
    E.1.2Classification code 10070667
    E.1.2Term Leber's congenital amaurosis
    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
    The primary objective of this study is to determine whether non-simultaneous, bilateral, subretinal
    administration of AAV2-hRPE65v2 improves the ability to navigate as measured by mobility
    testing in adults and children, three years of age or older. Mobility test performance
    one year following vector administrations will be compared to subjects’ pre-administration,
    baseline mobility test performance; independent, masked reviewers will be trained to assess ability to navigate.
    E.2.2Secondary objectives of the trial
    The secondary objective of this study is to continue to assess the safety and tolerability of AAV2-hRPE65v2.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Male and female subjects of any ethnic group are eligible for participation in this study, providing
    they meet the following criteria:
    1. Willingness to adhere to protocol and long-term follow-up as evidenced by written informed consent or parental permission and subject assent (where applicable).
    2. Diagnosis of LCA due to RPE65 mutations; molecular diagnosis is to be performed, or confirmed, by a CLIA-certified laboratory.
    3. Age three years old or older.
    4. Visual acuity worse than 20/60 (both eyes) and/or visual field less than 20 degrees in any meridian as measured by III4e isopter or equivalent (both eyes).
    5. Sufficient viable retinal cells as determined by non-invasive means, such as optical coherence tomography (OCT) and/or ophthalmoscopy. Must have either: 1) an area of retina within the posterior pole of >100 μm thickness shown on OCT; 2) >3 disc areas of retina without atrophy or pigmentary degeneration within the posterior pole; or 3)
    remaining visual field within 30 degrees of fixation as measured by III4e isopter or equivalent.
    6. Subjects must be evaluable on mobility testing (the primary efficacy endpoint) to be eligible for the study. Evaluable is defined as:
    a. The ability to perform mobility testing within the luminance range evaluated in the study. Individuals must receive an accuracy score of ≤ 1 during screening mobility
    testing at 400 lux or less to be eligible; individuals with an accuracy score of > 1 on all screening mobility test runs at 400 lux, or those who refuse to perform mobility testing at screening, will be excluded.
    b. The inability to pass mobility testing at 1 lux. Individuals must fail screening mobility testing at 1 lux to be eligible; individuals that pass one or more screening mobility test runs at 1 lux will be excluded.
    E.4Principal exclusion criteria
    1. Unable or unwilling to meet requirements of the study, including receiving bilateral
    subretinal vector administrations.
    2. Any prior participation in a study in which a gene therapy vector was administered.
    3. Participation in a clinical study with an investigational drug in the past six months.
    4. Use of retinoid compounds or precursors that could potentially interact with the biochemical activity of the RPE65 enzyme; individuals who discontinue use of these compounds for 18 months may become eligible.
    5. Prior intraocular surgery within six months.
    6. Known sensitivity to medications planned for use in the peri-operative period.
    7. Pre-existing eye conditions or complicating systemic diseases that would preclude the planned surgery or interfere with the interpretation of study. Complicating systemic diseases would include those in which the disease itself, or the treatment for the disease, can alter ocular function. Examples are malignancies whose treatment could affect central nervous system function (for example: radiation treatment of the orbit; leukemia with CNS/optic nerve involvement). Subjects with diabetes or sickle cell disease would be excluded if they had any manifestation of advanced retinopathy (e.g., macular edema or
    proliferative changes). Also excluded would be subjects with immunodeficiency (acquired
    or congenital) as there could be susceptibility to opportunistic infection (such as CMV retinitis).
    8. Individuals of childbearing potential who are pregnant or unwilling to use effective
    contraception for four months following vector administration.
    9. Individuals incapable of performing mobility testing (the primary efficacy endpoint) for
    reason other than poor vision, including physical and attentional limitations.
    10. Any other condition that would not allow the potential subject to complete follow-up examinations during the course of the study or, in the opinion of the investigator, makes the potential subject unsuitable for the study.
    E.5 End points
    E.5.1Primary end point(s)
    Mobility testing
    E.5.1.1Timepoint(s) of evaluation of this end point
    One year
    E.5.2Secondary end point(s)
    Additional visual/retinal function tests
    E.5.2.1Timepoint(s) of evaluation of this end point
    One year
    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) No
    E.7.1.1First administration to humans No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over Yes
    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 Yes
    E.8.2.3.1Comparator description
    Subjects in control group crossover receive IMP after at least one year from baseline evaluation
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 Will this trial be conducted at a single site globally? No
    E.8.4 Will this trial be conducted at multiple sites globally? Yes
    E.8.6 Trial involving sites outside the EEA
    E.8.6.2Trial being conducted completely outside of the EEA Yes
    E.8.6.3Specify the countries outside of the EEA in which trial sites are planned
    United States
    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.8.9.2In all countries concerned by the trial years15
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 20
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 17
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 3
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 11
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Paediatric subjects under age incapable of giving consent personally.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 27
    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)
    Subjects will be monitored annually for a period of 15 years from IMP administration.
    G. Investigator Networks to be involved in the Trial
    H.4 Third Country in which the Trial was first authorised
    H.4.1Third Country in which the trial was first authorised: United States
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