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    Summary
    EudraCT Number:2016-005000-26
    Sponsor's Protocol Code Number:4658-us-201
    Clinical Trial Type:Outside EU/EEA
    Date on which this record was first entered in the EudraCT database:2017-03-16
    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 number2016-005000-26
    A.3Full title of the trial
    A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Efficacy, Safety, Tolerability, and Pharmacokinetics Study of AVI-4658 (Eteplirsen), a Phosphorodiamidate Morpholino Oligomer, Administered Over 28 Weeks in the Treatment of Ambulant Subjects with Duchenne Muscular Dystrophy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A research study of a new investigational medicinal product for the treatment of patients with Duchenne Muscular Dystrophy.
    A.4.1Sponsor's protocol code number4658-us-201
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01396239
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/279/2016
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorSarepta 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 supportSarepta Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSarepta Therapeutics, Inc.
    B.5.2Functional name of contact pointMedical Director
    B.5.3 Address:
    B.5.3.1Street Address215 First Street
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post code02142
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1617274-4000
    B.5.6E-mailtrialinfo@sarepta.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 Yes
    D.2.1.1.1Trade name Exondys 51
    D.2.1.1.2Name of the Marketing Authorisation holderSarepta Therapeutics, Inc.
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEMEA/OD/049/08
    D.3 Description of the IMP
    D.3.1Product nameEteplirsen Injection
    D.3.2Product code AVI-4658
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAVI-4658
    D.3.9.1CAS number 1173755-55-9
    D.3.9.2Current sponsor codeAVI-4658
    D.3.9.3Other descriptive nameETEPLIRSEN
    D.3.9.4EV Substance CodeSUB129287
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    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) No
    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 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 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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboConcentrate for solution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping
    E.1.1.1Medical condition in easily understood language
    Duchenne muscular dystrophy
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.1
    E.1.2Level PT
    E.1.2Classification code 10013801
    E.1.2Term Duchenne muscular dystrophy
    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 the efficacy, safety, tolerability, and pharmacokinetics (PK) of AVI-4658 (eteplirsen) in subjects diagnosed with Duchenne muscular dystrophy (DMD).
    E.2.2Secondary objectives of the trial
    Not applicable
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Be a male with DMD and have an out-of-frame deletion(s) that may be corrected by skipping exon 51.

    2. Be between the ages of 7 and 13 years, inclusive.

    3. Have stable cardiac function and stable pulmonary function.

    4. Be receiving treatment with oral corticosteroids and have been on a stable dose for at least 24 weeks before study entry.

    5. Have intact right and left biceps muscles or an alternative upper arm muscle group.

    6. Achieve an average distance within 200m and 400m ±10% (i.e. within 180m and 440m) while walking independently over six minutes.

    7. Have a left ventricular ejection fraction (LVEF) of >40% based on the ECHO that is obtained at the screening visit (Visit 1). A subject who has abnormal ECHO findings but who has an LVEF of >40% may be enrolled in the study at the Investigator’s discretion; however, the subject must have been receiving stable doses of ACE inhibitors or β-blockers for at least 24 weeks before study entry.
    E.4Principal exclusion criteria
    1. Use of any pharmacologic treatment, other than corticosteroids, that might have an effect on muscle strength or function within 12 weeks before study entry (e.g., growth hormone, anabolic steroids).

    2. Previous treatment with the experimental agents eteplirsen, BMN-195, or PRO051.

    3. Previous treatment with any other experimental agents or participation in any other DMD interventional clinical study within 12 weeks before entry into this study; including use of the shock training system (STS) or planned use during this study.

    4. Surgery within 3 months before study entry or planned surgery at any time during this study.

    5. Presence of other clinically significant illness at the time of study entry, including significant renal dysfunction, or average heart rate during screening Holter monitoring in excess of 110 bpm or QTc >450 ms.

    6. Use of any aminoglycoside antibiotic within 12 weeks before the screening visit (Visit 1) or need for use of an aminoglycoside antibiotic during the study.
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline in the percentage of dystrophin-positive fibers as measured in muscle biopsy tissue using immunohistochemistry (IHC) at Week 12 for the 50 mg/kg/wk eteplirsen and matching placebo groups (Groups 1 and 3a) and at Week 24 for the 30 mg/kg/wk eteplirsen and matching placebo groups (Groups 2 and 3b).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 12
    Week 24
    E.5.2Secondary end point(s)
    Additional biopsy-related endpoints include the change from baseline to Week 12 for Groups 1 and 3a and to Week 24 for Groups 2 and 3b in:
    dystrophin intensity levels as measured by IHC
    total dystrophin protein levels as measured by Western blot analysis
    exon skipping as measured by reverse transcription polymerase chain reaction (RT-PCR)
    CD3, CD4, and CD8 lymphocyte counts as measured by IHC

    Functional efficacy endpoints include the change from baseline to week 24 in the:
    6-Minute Walk Test (6MWT)
    Timed 4-Step Test
    Maximum Voluntary Isometric Contraction Test (MVICT)
    North Star Ambulatory Assessment (NSAA) total score, and NSAA components including the Timed
    10-Meter Run and rise time
    9-Hole Peg Test
    Pulmonary Function Testing (PFT) including forced vital capacity (FVC), percent predicted FVC (%FVC), forced expiratory volume in 1 second (FEV1), percent predicted FEV1 (%FEV1), FEV1/FVC ratio; maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP)

    An additional endpoint is the change from baseline to week 24 on the Pediatric Quality of Life Inventory (PedsQL).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 12
    Week 24
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    After week 25 placebo patients receive either 30mg/kg or 50mg/kg eterplirsen
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 Will this trial be conducted at a single site globally? Yes
    E.8.4 Will this trial be conducted at multiple sites globally? No
    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 months8
    E.8.9.2In all countries concerned by the trial days11
    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: 12
    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: 12
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female No
    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 No
    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
    Males between the ages of 7 and 13, inclusive
    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 12
    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)
    Patients completing the trial have the option to enroll in the 4658-us-202 study (Open-Label, Multiple-Dose, Efficacy, Safety, and Tolerability Study of Eteplirsen in Subjects with Duchenne Muscular Dystrophy who Participated in Study 4658-us-201)
    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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