Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42869   clinical trials with a EudraCT protocol, of which   7063   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).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2017-004087-35
    Sponsor's Protocol Code Number:AVXS-101-CL-304
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2018-05-08
    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
    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 ConcernedUK - MHRA
    A.2EudraCT number2017-004087-35
    A.3Full title of the trial
    A Global Study of a Single, One-Time Dose of AVXS-101 Delivered to Infants with Genetically Diagnosed and Pre-symptomatic Spinal Muscular Atrophy with Multiple Copies of SMN2
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Single dose gene replacement therapy clinical trial for infants with genetically diagnosed and pre-symptomatic Spinal Muscular Atrophy
    A.3.2Name or abbreviated title of the trial where available
    SPR1NT
    A.4.1Sponsor's protocol code numberAVXS-101-CL-304
    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 SponsorNovartis Gene Therapies, 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 supportNovartis Gene Therapies, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Gene Therapies, Inc.
    B.5.2Functional name of contact pointSr. Global Trial Operations Manager
    B.5.3 Address:
    B.5.3.1Street Address2275 Half Day Road, Suite 200
    B.5.3.2Town/ cityBannockburn IL
    B.5.3.3Post code60015
    B.5.3.4CountryUnited States
    B.5.4Telephone number1224500 2097
    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/3/15/1509
    D.3 Description of the IMP
    D.3.1Product nameAVXS-101 (previously known as scAAV9.CB.SMN)
    D.3.2Product code AVXS-101
    D.3.4Pharmaceutical form Infusion
    D.3.4.1Specific paediatric formulation Yes
    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 INNonasemnogene abeparvovec
    D.3.9.1CAS number 1922968-73-7
    D.3.9.2Current sponsor codeAVXS-101
    D.3.10 Strength
    D.3.10.1Concentration unit vector genomes (vg)/mL
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number20000000000000 to 60000000000000
    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
    Spinal Muscular Atrophy
    E.1.1.1Medical condition in easily understood language
    Spinal Muscular Atrophy
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Safety
    • Evaluate the safety of AVXS-101 through incidence of adverse events (AEs) and/or serious adverse events (SAEs)
    •Evaluate the safety of AVXS-101 based on the change from baseline in clinical laboratory parameters
    Efficacy objectives will be assessed independently for each cohort.
    Efficacy for patients with bi-allelic SMN1 deletions and 2 copies of SMN2:
    •Assess the efficacy of AVXS-101 by demonstrating functional independent sitting for at least 30 seconds as defined by Bayley Scales of Infant and Toddler Development© Version 3 (BSIDv03) Gross Motor Subset Item #26 at any visit up to 18 months of age
    Efficacy for patients with 3 copies of SMN2:
    •Assess the efficacy of AVXS-101 based on the proportion of patients achieving the ability to stand without support for at least three seconds as defined by Bayley Scales of Infant and Toddler Development© Version 3 (BSIDv03) Gross Motor Subset Item #40 at any visit up to 24 months of age
    E.2.2Secondary objectives of the trial
    Efficacy for patients with 2 copies of SMN2:
    •Determine the efficacy of AVXS-101 based on survival, defined as avoidance of death or the requirement of permanent ventilation in the absence of acute illness or perioperatively as assessed at 14 months of age
    •Assess efficacy of AVXS-101 by demonstrating the ability to maintain weight at or above the third percentile without need for non-oral/mechanical feeding support at any visit up to 18 months of age

    Efficacy for patients with 3 copies of SMN2:
    •Assess the efficacy of AVXS-101 by demonstrating the ability to walk alone defined as the ability to take at least five steps independently displaying coordination and balance, as defined by BSIDv03 Gross Motor Subtest Item #43, at any visit up to 24 months of age
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    All patients:
    •Age ≤6 weeks (≤42 days) at time of dose
    •Ability to tolerate thin liquids as demonstrated through a formal bedside swallowing test
    •Compound muscle action potential (CMAP) ≥2 mV at Baseline
    •Gestational age of 35 to 42 weeks
    •Genetic diagnosis as described below, obtained from an acceptable newborn or pre-natal screening test method

    Patients with 2 copies of SMN2
    •Patients with pre-symptomatic SMA Type 1 as determined by the following features:
    •Bi-allelic deletion of SMN1
    •2 copies of SMN2

    Patients with 3 copies of SMN2
    •Patients with pre-symptomatic SMA Type 2 as determined by the following features:
    •Bi-allelic deletion of SMN1
    •3 copies of SMN2
    E.4Principal exclusion criteria
    •Weight at screening visit <2 kg
    •Hypoxemia (oxygen saturation <96% awake or asleep without any supplemental oxygen or respiratory support) at the screening visit
    •Any clinical signs or symptoms at screening or immediately prior to dosing that are, in the opinion of the Investigator, strongly suggestive of SMA (e.g., tongue fasciculation, hypotonia, areflexia)
    •Tracheostomy or current prophylactic use or requirement of non invasive ventilatory support at any time and for any duration prior to screening or during the screening period
    •Patients with signs of aspiration/inability to tolerate non thickened liquids based on a formal swallowing test performed as part of screening or patients receiving any non-oral feeding method
    •Clinically significant abnormal laboratory values (GGT, ALT and AST, or total bilirubin > 2 x the ULN, creatinine ≥ 1.0 mg/dL, haemoglobin [Hgb] < 8 or > 18 g/dL; white blood cell [WBC] > 20,000 per cmm) prior to gene replacement therapy. Patients with an elevated bilirubin level that is unequivocally the result of neonatal jaundice shall not be excluded.
    •Patients with any other clinically significant abnormalities in hematology or clinical chemistry parameters as determined by the investigator or medical monitor
    •Treatment with an investigational or commercial product, including nusinersen, given for the treatment of SMA. This includes any history of gene therapy, prior antisense oligonucleotide treatment, or cell transplantation.
    •Patients whose weight-for-age is below the third percentile based on World Health Organization (WHO) Child Growth Standards
    •Serious non respiratory tract illness requiring systemic treatment and/or hospitalization within 2 weeks prior to screening
    •Upper or lower respiratory infection requiring medical attention, medical intervention, or increase in supportive care of any manner within 4 weeks prior to dosing
    •Previous, planned or expected major surgical procedure including scoliosis repair surgery/procedure during the study assessment period
    •Concomitant use of any of the following: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, immunosuppressive therapy within 4 weeks prior to gene replacement therapy (e.g., corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, IV immunoglobulin, rituximab)
    •Anti AAV9 antibody titer >1:50 as determined by Enzyme linked Immunosorbent Assay (ELISA) binding immunoassay
    E.5 End points
    E.5.1Primary end point(s)
    Criteria for Evaluation:
    Safety:
    Primary:
    •Incidence of adverse events (AEs) and/or serious adverse events (SAEs)
    •Change from baseline in clinical laboratory parameters

    Efficacy objectives will be assessed independently for each cohort.

    Efficacy for patients with 2 copies of SMN2:
    Primary:
    •Proportion of patients achieving the development milestone of functional independent sitting at any visit up to 18 months of age

    Efficacy for patients with 3 copies of SMN2:
    Primary:
    •Proportion of patients achieving the ability to stand without support for at least three seconds at any visit up to 24 months of age
    E.5.1.1Timepoint(s) of evaluation of this end point
    Patients with 2 copies of SMN2:
    18 months of age
    Patients with 3 copies of SMN2:
    24 months of age
    E.5.2Secondary end point(s)
    Patients with 2 copies of SMN2:
    •Proportion of patients that have survived and have not required permanent ventilation in the absence of acute illness or perioperatively assessed at 14 months of age
    •Proportion of patients that have achieved the ability to maintain weight at or above the third percentile without need for non-oral/mechanical feeding support at any visit up to 18 months of age


    Patients with 3 copies of SMN2:
    •Proportion of patients demonstrating the ability to walk alone defined as the ability to take at least five steps independently displaying coordination and balance at any visit up to 24 months of age
    E.5.2.1Timepoint(s) of evaluation of this end point
    Patients with 2 copies of SMN2:
    •Proportion of patients that have survived and have not required permanent ventilation assessed at 14 months of age
    •Proportion of patients that have achieved the ability to maintain weight at or above the third percentile without need for non-oral/mechanical feeding support at any visit up to 18 months of age

    Patients with 3 copies of SMN2:
    •24 months of age
    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 No
    E.8.1.1Randomised No
    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 No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Open-label, single-arm, single-dose
    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 Yes
    E.8.5.1Number of sites anticipated in the EEA6
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Belgium
    Canada
    Germany
    Israel
    Italy
    Japan
    Korea, Democratic People's Republic of
    Netherlands
    Spain
    Taiwan
    United Kingdom
    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.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    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: 29
    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) Yes
    F.1.1.3.1Number of subjects for this age range: 14
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 15
    F.1.1.5Children (2-11years) No
    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 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 Information not present in EudraCT
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    F.3.3.3Pregnant women Information not present in EudraCT
    F.3.3.4Nursing women Information not present in EudraCT
    F.3.3.5Emergency situation Information not present in EudraCT
    F.3.3.6Subjects incapable of giving consent personally Information not present in EudraCT
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 12
    F.4.2.2In the whole clinical trial 29
    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)
    After the End of Trial Visit, eligible patients will be asked to rollover into the long-term follow up trial.
    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 Decision2018-07-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-08-24
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA