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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   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 on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:2021-006709-31
    Sponsor's Protocol Code Number:COAV101B12302
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-07-15
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2021-006709-31
    A.3Full title of the trial
    Phase IIIb, open-label, single-arm, multi-center study to evaluate the safety, tolerability and efficacy of OAV101 administered intrathecally (1.2 x 1014 vector genomes) to participants 2 to 12 years of age with spinal muscular atrophy (SMA) who have discontinued treatment with nusinersen (Spinraza®) or risdiplam (Evrysdi®)
    Estudio de fase IIIb, multicéntrico, abierto y de un único grupo en el que se evalúan la seguridad, la tolerabilidad y la eficacia de OAV101 administrado intratecalmente (1,2 x 1014 genomas vectoriales) a participantes de 2 a 12 años de edad con atrofia muscular espinal (AME) que hayan discontinuado el tratamiento con nusinersen (Spinraza®) o risdiplam (Evrysdi®).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase IIIb, open-label, multi-center study to evaluate safety, tolerability and efficacy study of OAV101 administered intrathecally to participants with spinal muscular atrophy (SMA) who have discontinued treatment with nusinersen or risdiplam
    Estudio de fase IIIb, multicéntrico, abierto en el que se evalúan la seguridad, la tolerabilidad y la eficacia de OAV101 administrado intratecalmente a participantes con atrofia muscular espinal que hayan discontinuado el tratamiento con nusinersen o risdiplam
    A.3.2Name or abbreviated title of the trial where available
    STRENGTH
    STRENGTH
    A.4.1Sponsor's protocol code numberCOAV101B12302
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/015/2022
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNovartis Farmacéutica, S.A.
    B.1.3.4CountrySpain
    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 Farmacéutica, S.A.
    B.5.2Functional name of contact pointTrial Monitoring Organization (TMo)
    B.5.3 Address:
    B.5.3.1Street AddressGran Via de les Corts Catalanes, 764
    B.5.3.2Town/ cityBarcelona
    B.5.3.3Post code08013
    B.5.3.4CountrySpain
    B.5.4Telephone number34 90 0353036
    B.5.5Fax number34 93 2479903
    B.5.6E-maileecc.novartis@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 Gene Therapies EU Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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.3.1Product nameOAV101
    D.3.2Product code OAV101
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPIntrathecal 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 codeOAV101
    D.3.9.3Other descriptive namepreviously termed sc.AAV9.CB.SMN and AVXS-101
    D.3.9.4EV Substance CodeSUB193254
    D.3.10 Strength
    D.3.10.1Concentration unit Vector genome
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40000000000000
    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
    Atrofia Muscular Espinal
    E.1.1.1Medical condition in easily understood language
    Spinal Muscular Atrophy
    Atrofia Muscular Espinal
    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 characterize the safety and tolerability of OAV101 intrathecal (IT) over a 52-week period in patients with SMA aged 2 to 12 years who have discontinued treatment with nusinersen (Spinraza®) or risdiplam (Evrysdi®).
    El objetivo principal de este estudio es caracterizar la seguridad y la tolerabilidad de OAV101 intratecal (IT) durante un periodo de 52 semanas en pacientes de 2 a 12 años de edad con AME que hayan discontinuado el tratamiento con nusinersen (Spinraza®) o risdiplam (Evrysdi®).
    E.2.2Secondary objectives of the trial
    The secondary objective of this study is to assess the efficacy of OAV101 IT on motor function and caregiver impact over a 52-week period in patients with SMA aged 2 to 12 years who have discontinued treatment with nusinersen (Spinraza®) or risdiplam (Evrysdi®).
    El objetivo secundario de este estudio es evaluar la eficacia de OAV101 IT en la función motora y el impacto en el cuidador durante un periodo de 52 semanas en pacientes de 2 a 12 años de edad con AME que hayan discontinuado el tratamiento con nusinersen (Spinraza®) o risdiplam (Evrysdi®).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    ● Written informed consent
    ● SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations and any copy of SMN2 gene
    ● Aged 2 to 12 years at time of Screening Visit 1
    ● Have had at least four loading doses of nusinersen (Spinraza®) or at least 3 months of treatment with risdiplam (Evrysdi®) at Screening
    ● Must be able to sit independently but must never have taken steps independently
    ● Diagnosed through newborn or neonatal screening or patients clinically diagnosed must have age of clinical symptom onset < 18 months
    ● Meets age-appropriate institutional criteria for use of anesthesia/sedation
    ● Female participants who are sexually active or have reached menarche must have a negative pregnancy test at Screening. Those females who are sexually active must also agree to use highly effective methods of contraception.
    - Consentimiento informado por escrito.
    - Diagnóstico de AME con mutaciones bialélicas en el gen SMN1 y cualquier copia del gen SMN2 basado en un análisis de mutación genética.
    - De 2 a 12 años de edad en el momento de la visita de selección 1.
    - Haber recibido al menos cuatro dosis de carga de nusinersen (Spinraza®) o bien tratamiento con risdiplam (Evrysdi®) durante al menos 3 meses en la selección.
    - Poder sentarse solos, pero nunca haber dado pasos de forma independiente.
    - Los pacientes diagnosticados en pruebas neonatales o los pacientes con un diagnóstico clínico deben tener <18 meses de edad al inicio de los síntomas clínicos.
    - Cumplir los criterios de edad establecidos por el centro para el uso de anestesia/sedación.
    - Las participantes que sean sexualmente activas o hayan llegado a la menarquia deben presentar un resultado negativo en una prueba de embarazo en la selección. Las mujeres que sean sexualmente activas también deberán aceptar utilizar métodos anticonceptivos altamente eficaces.
    E.4Principal exclusion criteria
    ● Excluding SMA, any medical condition considered clinically significant
    ● Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis
    ● Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer using an immunoassay is reported as elevated (reference to >1:50 or a validated result consistent with being elevated)
    ● Clinically significant abnormalities in test results during screening period and/or at Baseline
    ● Platelet count less than the lower limit of normal (LLN), or platelet transfusion within 1 month at Screening Visit 1
    ● Abnormal coagulation panel results at Screening
    ● Hepatic dysfunction (i.e. alanine aminotransferase (ALT), total bilirubin (TBL), gamma-glutamyl transferase (GGT) or glutamate dehydrogenase (GLDH) > upper limit of normal (ULN) at Screening (with the exception of isolated AST elevation: in the absence of other liver laboratory abnormalities, isolated elevated AST is not considered exclusionary)
    ● Contraindications for lumbar puncture procedure
    ● At Baseline (Day-1), participants are excluded if they received:
    ●nusinersen (Spinraza®) within 4 months at Baseline
    ● risdiplam (Evrysdi®) within 15 days at Baseline
    ● Vaccinations 2 weeks prior to administration of OAV101
    ● Hospitalization for a pulmonary event, or for nutritional support within 2 months prior to Screening or inpatient major surgery planned.
    ● Presence of the following:
    ● An active infectious process requiring systemic antiviral or antimicrobial therapy at any time between Screening Visit 1 and OAV101 administration, or
    ● An active but untreated viral or bacterial infectious process at any time between Screening Visit 1 and administration of OAV101, or
    ● Any febrile illness within two weeks prior to Screening Visit 1 and up to administration of OAV101
    ● Requiring invasive ventilation, awake noninvasive ventilation for > 6 hours during a 24-hour period, noninvasive ventilation for >12 hours during a 24-hour period or requiring tracheostomy, at Screening and up to OAV101 administration
    ● Concomitant use of any of the following medication categories within 90 days prior to administration of OAV101
    ● Ongoing immunosuppressive therapy (e.g., corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab), plasmapheresis, immunomodulators (e.g., adalimumab)
    ● History of hypersensitivity to any of the study treatments or its excipients or drugs of similar chemical classes
    - Cualquier enfermedad considerada de interés clínico excluyendo la AME.
    - Resultado positivo en una prueba del virus de la inmunodeficiencia humana (VIH), de hepatitis B o de hepatitis C.
    - El título de anticuerpos anti-virus adenoasociado de serotipo 9 (AAV9) usando un inmunoensayo se informa como elevado (referencia a >1:50 o un resultado validado consistente con estar elevado)
    - Anomalías de interés clínico en los resultados de las pruebas durante el periodo de la selección o en la basal.
    - Recuento de plaquetas por debajo del límite inferior de normalidad (LIN) o transfusión de plaquetas durante el mes anterior a la visita de selección 1.
    - Resultados anormales en las pruebas de coagulación en la selección.
    - Disfunción hepática (es decir, alanina aminotransferasa (ALT), bilirrubina total (BT), gamma glutamiltransferasa (GGT) o glutamato deshidrogenasa (GLDH) >límite superior de normalidad (LSN) en la selección (con la excepción de elevación aislada de AST: si no presentan otras anomalías analíticas hepáticas, la AST elevada aislada no se considera excluyente).
    - Contraindicaciones para el procedimiento de punción lumbar.
    - En la basal (día -1), los participantes están excluidos si han recibido:
    -- Nusinersen (Spinraza®) durante los 4 meses anteriores a la basal.
    -- Risdiplam (Evrysdi®) durante los 15 días anteriores a la basal.
    - Vacunas 2 semanas antes de la administración de OAV101.
    - Hospitalización por un acontecimiento pulmonar o para apoyo nutricional durante los 2 meses anteriores a la selección o cirugía mayor prevista con ingreso hospitalario.
    - Presencia de:
    -- Un proceso infeccioso activo que requiera tratamiento antiviral o antimicrobiano sistémico en cualquier momento entre la visita de selección 1 y la administración de OAV101, o
    -- un proceso infeccioso vírico o bacteriano activo y sin tratar en cualquier momento entre la visita de selección 1 y la administración de OAV101, o
    -- cualquier enfermedad febril durante las dos semanas anteriores a la visita de selección 1 y hasta la administración de OAV101.
    - En la selección y hasta la administración de OAV10, requerir ventilación invasiva o ventilación no invasiva durante la vigilia durante >6 horas en un periodo de 24 horas, ventilación no invasiva durante >12 horas en un periodo de 24 horas o traqueotomía.
    - Uso concomitante de cualquiera de las siguientes categorías de medicamentos durante los 90 días anteriores a la administración de OAV101:
    -- Tratamiento en curso con inmunosupresores (p. ej., corticosteroides, ciclosporina, tacrolimus, metotrexato, ciclofosfamida, inmunoglobulina intravenosa o rituximab), plasmaféresis o inmunomoduladores (p. ej., adalimumab).
    - Antecedentes de hipersensibilidad a alguno de los tratamientos del estudio o sus excipientes o a fármacos de clases químicas similares.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoints for the primary objectives are: the number and percentage of participants reporting adverse events (AEs), related AEs, serious AEs and adverse events of special interest (AESIs) over a 52-week period.
    Las variables principales para los objetivos principales son: el número y el porcentaje de participantes que informaron eventos adversos (EA), EA relacionados, EA graves y eventos adversos de especial interés (AESI) durante un período de 52 semanas.
    E.5.1.1Timepoint(s) of evaluation of this end point
    52 weeks
    52 semanas
    E.5.2Secondary end point(s)
    The secondary endpoints for the secondary objective questions of interest are:
    ● What is the change from baseline to Week 52 visit in the Hammersmith Functional Motor Scale Expanded (HFMSE) total score?
    ● What is the change from baseline to Week 52 visit in the Revised Upper Limb Module (RULM) total score?
    ● What is the change from baseline to Week 52 visit in Assessment of Caregiver Experience in Neuromuscular Disease (ACEND) instrument score?
    Las variables secundarias de las cuestiones de interés del objetivo secundario son:
    - ¿Cuál es el cambio desde la basal hasta la visita de la semana 52 en la puntuación total obtenida en la evaluación Hammersmith Functional Motor Scale Expanded (HFMSE)?
    - ¿Cuál es el cambio desde la basal hasta la visita de la semana 52 en la puntuación total obtenida en la evaluación Revised Upper Limb Module (RULM)?
    - ¿Cuál es el cambio desde la basal hasta la visita de la semana 52 en la puntuación obtenida en la evaluación Assessment of Caregiver Experience in Neuromuscular Disease (ACEND)?
    E.5.2.1Timepoint(s) of evaluation of this end point
    52 weeks
    52 semanas
    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
    Tolerabilidad
    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 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 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 EEA8
    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
    Canada
    Japan
    United States
    France
    Netherlands
    Spain
    Germany
    Italy
    Belgium
    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.
    La finalización del estudio se define cuando el último participante finaliza su visita de finalización del estudio y cualquier evaluación repetida asociada a esa visita, ha sido documentada y seguida adecuadamente por el investigador o, en el caso de una decisión de finalización anticipada del estudio, la fecha de esa decisión.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months11
    E.8.9.1In the Member State concerned days21
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months1
    E.8.9.2In all countries concerned by the trial days10
    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: 28
    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: 24
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 4
    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 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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 13
    F.4.2.2In the whole clinical trial 28
    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)
    Participants from this study will be offered to participate in a planned long-term follow up (upto 15 years) study. The planned long-term study does not involve drug administration.
    A los participantes de este estudio se les ofrecerá participar en un estudio de seguimiento planificado a largo plazo (hasta 15 años). El estudio planificado a largo plazo no implica la administración de fármacos.
    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 Decision2022-11-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-08-05
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat May 04 13:56:57 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA