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    Summary
    EudraCT Number:2023-000864-67
    Sponsor's Protocol Code Number:COAV101A1IC01
    Clinical Trial Type:Outside EU/EEA
    Date on which this record was first entered in the EudraCT database:2024-02-02
    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 number2023-000864-67
    A.3Full title of the trial
    A Phase IV Open-label, single-arm, single-dose, multicenter study to evaluate the saFEty, toLerability and effIcacy of gene replacement therapy with intravenous OAV101(AVXS101) in pediatric patients from Latin America with spinal muscular atrophy (SMA) – OFELIA
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Safety and efficacy of intravenous OAV101 (AVXS-101) in pediatric patients with spinal muscular atrophy (SMA)
    A.3.2Name or abbreviated title of the trial where available
    OFELIA
    A.4.1Sponsor's protocol code numberCOAV101A1IC01
    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 BIOCIÊNCIAS S.A
    B.1.3.4CountryBrazil
    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 Pharma AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Pharma AG
    B.5.2Functional name of contact pointClinical Disclosure Office
    B.5.3 Address:
    B.5.3.1Street AddressLichtstrasse 35
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4056
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number41613241111
    B.5.6E-mailnovartis.email@novartis.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 Zolgensma
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Biocencias SA
    D.2.1.2Country which granted the Marketing AuthorisationBrazil
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEMA/OD/028/15
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPIntravenous 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) 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 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
    Spinal Muscular Atrophy
    E.1.1.1Medical condition in easily understood language
    Spinal Muscular Atrophy
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10041582
    E.1.2Term Spinal muscular atrophy
    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 assess the safety and tolerability of IV OAV101 over a 18-month period in patients with SMA weighing less or equal of 17 kg at the time of dose Endpoints: • Evaluation of treatment emergent AEs and SAEs • Evaluation of important identified and important potential risks • Evaluate changes from baseline in vital signs, cardiac safety assessments, and clinical laboratory results
    E.2.2Secondary objectives of the trial
    To determine the efficacy of IV OAV101 at 6, 12- and 18-months post infusion in participants with SMA ≤ 24 months and weighing ≤ 17kg as measured by change from baseline in: Achievement of developmental motor milestones according to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent/assent obtained prior to any assessment performed
    2. Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and any copy of SMN2 gene.
    3. Age ≤ 24 months of age at time of treatment Weight ≤17 kg at the time of Screening Period
    4. Naive to treatment or have discontinued an approved drug/therapy
    5. Up-to date on recommended childhood vaccinations and RSV prophylaxis with palivizumab (also known as Synagis), per local standard of care
    E.4Principal exclusion criteria
    1. Previous use of OAV101 or any AAV9 gene therapy
    2. BMI < 3rd percentile based on WHO Child Growth Standard
    3. Participant with history of aspiration
    pneumonia or signs of aspiration (eg, coughing or sputtering of food) within 4 weeks prior to Screening
    4. Participant dependent on gastrostomy feeding tube for 100% of nutritional intake.
    4. Anti-AAV9 antibody titer > 1:50 as determined by ligand binding immunoassay at the time of screening
    5. History of gene therapy, hematopoietic transplantation, or solid organ transplantation
    6. Inability to take corticosteroids
    7. Concomitant use of immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, or immunosuppressive therapy within 3 months prior to gene replacement therapy (eg, cyclosporine, tacrolimus, methotrexate, rituximab cyclophosphamide, IV immunoglobulin)
    8. Requiring invasive ventilation, tracheostomy or daytime non-invasive ventilation (standard of care nocturnal BiPAP is not considered exclusionary)
    9. Administration of vaccines 2 weeks prior to infusion of OAV101
    10. Awake hypoxemia (O2 saturation <95%) or awake oxygen saturation level decrease between screening and dosing that is clinically significant, as per investigator judgment
    11. Clinically significant neurologic or neuromuscular conditions other than SMA as determined by the principal Investigator
    12. Clinically significant abnormalities in laboratory test results at Screening as determined by the Investigator
    13. Hepatic dysfunction (i.e. AST, ALT, bilirubin, GGT or GLDH, ≥ ULN; CTCAE ≥ 1) at Screening (with the exception of isolated AST elevation: in the absence of other liver laboratory abnormalities, isolated AST elevation is not considered exclusionary)
    14. Excluding SMA, any medically unstable condition considered clinically significant by the Investigator, including cardiomyopathy, hepatic dysfunction, kidney disorder, endocrine disorder, GI disorders, metabolic disorders, severe respiratory compromise and significant brain abnormalities at either Screening or Baseline visits that, in the opinion of the investigator, would interfere with the overall interpretation of safety or efficacy of the study
    15. Presence of a confirmed or suspected active infectious process from screening and up to dose administration
    17. Previously treated with nusinersen (Spinraza®) within 4 months prior to Screening
    18. Previously treated with risdiplam (EvrysdiTM) within 15 days prior to Screening (washout period of at least 5 half-lives before Screening)
    19. Use of other investigational drugs within 5 half-lives of enrollment/initiation of study treatment (select as appropriate) within 30 days (eg, small molecules) / or until the expected pharmacodynamic effect has returned to baseline (eg, biologics), whichever is longer; or longer if required by local regulations.
    20. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
    21. Documented any parental consanguinity (1st degree consanguinity).
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoints include:
     Evaluation of treatment emergent AEs and SAEs
     Evaluation of important identified and potential risks
     Evaluate changes from baseline in vital signs, cardiac safety assessments, and clinical laboratory results
    E.5.1.1Timepoint(s) of evaluation of this end point
    Incidence and severity for treatment emergent AEs and SAEs as well as important identified and important potential risks will be summarized overall in the safety set. The number and proportion of participants reporting a treatment emergent AE or SAE, including investigator and Sponsor causalities will be reported. Summaries will also be provided by MedDRA System Organ Class and Preferred Term.
    Changes from baseline in vital signs, and clinical laboratory, and procedure (eg ECG, echocardiogram) results will be summarized descriptively overall in the safety set. Mean, standard deviation, median, minimum, and maximum will be presented.
    E.5.2Secondary end point(s)
    Proportion of participants who achieve Development Motor Milestones according to the World Health Organization-Multicentre Growth Reference Study (WHO-MGRS) at 6, 12, and 18 months post-infusion
    E.5.2.1Timepoint(s) of evaluation of this end point
    At Baseline, 6, 12, and 18 months post-infusion
    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 Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    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 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.8.2.4Number of treatment arms in the trial1
    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
    Argentina
    Brazil
    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
    Study completion is defined as when the last participant finishes their Study Completion visit and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator or, in the event of an early study termination decision, the
    date of that decision.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    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: 16
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 16
    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 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 No
    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 16
    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 study completion eligible participants will be invited to enroll into a Registry study (RESTORE) to collect additional safety and efficacy data.
    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: Brazil
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