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    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.
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    Summary
    EudraCT Number:2017-000266-29
    Sponsor's Protocol Code Number:AVXS-101-CL-302
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2018-05-28
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2017-000266-29
    A.3Full title of the trial
    Phase 3, Open Label, Single Arm, Single Dose Gene Replacement Therapy Clinical Trial for Patients with Spinal Muscular Atrophy Type 1 with One or Two SMN2 Copies Delivering AVXS 101 by Intravenous Infusion
    Ensayo clínico de fase 3, abierto, de un solo brazo y dosis única de terapia de sustitución génica para pacientes con atrofia muscular espinal tipo 1 con una o dos copias de SMN2 mediante la liberación de AVXS-101 por infusión intravenosa
    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 Patients with Spinal Muscular Atrophy Type 1
    Dosis única de terapia de sustitución génica para pacientes con atrofia muscular espinal tipo 1
    A.4.1Sponsor's protocol code numberAVXS-101-CL-302
    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 SponsorAveXis, 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 supportAveXis, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAveXis, 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
    B.5.6E-mailswilliamson630@avexis.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/3/15/1509
    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
    Replacement Therapy Clinical Trial for Patients with Spinal Muscular Atrophy Type 1
    Ensayo clínico de terapia de sustitución para pacientes con atrofia muscular espinal tipo 1
    E.1.1.1Medical condition in easily understood language
    Patients with Spinal Muscular Atrophy Type 1
    Pacientes con atrofia muscular espinal tipo 1
    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
    Determine efficacy by demonstrating achievement of developmental milestone of sitting without support up to 18 months of age as defined by WHO Motor Developmental Milestones
    Determinar la eficacia al demostrar el logro del hito de desarrollo de sentarse sin ayuda hasta los 18 meses de edad, tal y como establecen los hitos de desarrollo motor de la OMS.
    E.2.2Secondary objectives of the trial
    Determine efficacy based on survival at 14 months of age. Survival is defined by the avoidance of combined endpoint of either (a) death or (b) permanent ventilation which is defined by tracheostomy or by the requirement of ≥ 16 hours of respiratory assistance per day (via non invasive ventilatory support) for ≥ 14 consecutive days in the absence of an acute reversible illness, excluding perioperative ventilation. Permanent ventilation, so defined, is considered a surrogate for death.
    Determinar la eficacia basada en la supervivencia a los 14 meses de edad. La supervivencia se define como la elusión de criterios de valoración combinados, ya sea (a) muerte o (b) ventilación permanente, que se define por traqueostomía o por la necesidad de ≥ 16 horas de asistencia respiratoria al día (mediante asistencia ventilatoria no invasiva) durante ≥ 14 días consecutivos en ausencia de enfermedad reversible aguda, a excepción de la ventilación perioperatoria. La ventilación permanente, según su definición, se considera un desencadenante indirecto de la muerte
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Patients with SMA Type 1 as determined by the diagnosis of SMA based on gene mutation analysis with biallelic SMN1 mutations (deletion or point mutations) and one or two copies of SMN2 [inclusive of the known SMN2 gene modifier mutation (c.859G>C)]
    • Patients must be < 6 months (< 180 days) of age at the time of AVXS-101 infusion.
    • Patients must have a swallowing evaluation test performed prior to administration of gene replacement therapy.
    * Los pacientes con AME tipo 1, según el diagnóstico de la AME en base al análisis de mutación genética con mutaciones de SMN1 bialélicas (deleción o mutaciones puntuales) y una o dos copias de SMN2 [incluida la mutación conocida del gen modificador SMN2 (c.859G>C)].
    * Los pacientes deben ser < 6 meses (< 180 días) de edad en el momento de la infusión de AVXS-101.
    * Los pacientes deben realizar una prueba de evaluación de deglución antes de administrar la terapia de sustitución génica.
    E.4Principal exclusion criteria
    * Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry < 95% saturation at screening
    - Pulse oximetry saturation must not decrease ≥ four (4) percentage points between screening and dosing with confirmatory oximetry reading
    - Patients may be put on non-invasive ventilatory support for less than 12 hours per day at the discretion of their physician or trial staff.
    • Use or requirement of non-invasive ventilatory support for 12 or more hours daily in the two weeks prior to dosing.
    • Patient with signs of aspiration based on a swallowing test or whose weight-for-age falls below the 3rd percentile based on World Health Organization (WHO) Child Growth Standards [27] and is unwilling to use an alternative method to oral feeding.
    • Participation in recent SMA treatment clinical study (with the exception of observational cohort studies or non-interventional studies) or receipt of an investigational or commercial compound, product, or therapy administered with the intent to treat SMA (e.g., nusinersen, valproic acid) at any time prior to screening for this study. Oral β-agonists must be discontinued at least 30 days before gene therapy dosing. Inhaled albuterol specifically prescribed for the purposes of respiratory (bronchodilator) management is acceptable.
    • Patient < 35 weeks gestational age at time of birth.
    * Uso de asistencia ventilatoria invasiva (traqueotomía con presión positiva) o pulsioximetría con una saturación<95 % en el período de selección.
    - La saturación de la pulsioximetría no debe disminuir ≥ cuatro (4) puntos porcentuales entre la selección y la administración de la dosis, con una lectura de oxitometría de confirmación.
    - Los pacientes deben recibir asistencia respiratoria no invasiva durante menos de 12 horas por día, a discreción del médico o del personal del ensayo.
    * Uso o necesidad de asistencia respiratoria no invasiva durante 12 horas o más al día las dos semanas previas a la administración de la dosis.
    * Los pacientes que muestren síntomas de aspiración en la prueba de deglución o cuyo peso por edad sea inferior al tercer percentil según los Patrones de crecimiento infantil[27] de la OMS y que no estén dispuestos a utilizar un método alternativo a la alimentación oral.
    * Participación en un ensayo clínico reciente de tratamiento de la AME (a excepción de estudios de cohorte observacionales o no intervencionistas) o tratamiento con un compuesto, producto o terapia en fase de investigación o comercialización que se administre con la intención de tratar la AME (p. ej., nusinersen o ácido valproico) en cualquier momento antes de la selección para este ensayo. La ingesta de agonistas β orales debe interrumpirse al menos 30 días antes de la administración de la dosis de terapia génica. El albuterol inhalado prescrito específicamente para el tratamiento respiratorio (broncodilatador) es aceptable.
    * El paciente tiene una edad gestacional < 35 semanas en el momento del nacimiento.
    E.5 End points
    E.5.1Primary end point(s)
    • Proportion of symptomatic SMA Type 1 patients who are homozygous negative for SMN1 exon 7 and have two copies of SMN2 without the SMN2 genetic modifier that achieve the ability to sit without support for at least 10 seconds up to and including the 18 months of age trial visit. Sitting without support is defined by the World Health Organization Multicentre Growth Reference Trial (WHO MGRS), confirmed by video recording, as a patient who sits up straight with head erect for at least 10 seconds; child does not use arms or hands to balance body or support position.
    •Proporción de pacientes con AME tipo 1 sintomática que son homocigotos negativos para el exón 7 de SMN1 y tienen dos copias de SMN2 sin el modificador genético de SMN2 que logra la capacidad de sentarse sin ayuda durante al menos 10 segundos hasta e incluida la visita del ensayo de 18 meses de edad. Sentarse sin ayuda se define en el ensayo multicéntrico sobre el patrón de crecimiento (EMPC) de la OMS y se confirma mediante una videograbación en la que se muestre que el paciente se mantiene sentado derecho y con la cabeza erguida durante al menos 10 segundos; el niño no utiliza los brazos ni las manos para equilibrar el cuerpo o mantener la posición.
    E.5.1.1Timepoint(s) of evaluation of this end point
    18 months
    18 meses
    E.5.2Secondary end point(s)
    • Survival at 14 months of age amongst symptomatic SMA Type 1 patients who are homozygous negative for SMN1 exon 7 and have two copies of SMN2 without the SMN2 genetic modifier. Survival is defined by the avoidance of the combined endpoint of either (a) death or (b) permanent ventilation, which is defined by tracheostomy or by the requirement of ≥ 16 hours of respiratory assistance per day (via non‑invasive ventilatory support) for ≥ 14 consecutive days in the absence of an acute reversible illness, excluding perioperative ventilation. Permanent ventilation, so defined, is considered a surrogate for death.
    • Supervivencia a los 14 meses de edad entre los pacientes con AME tipo 1 sintomática que son homocigotos negativos para el exón 7 de SMN1 y tienen dos copias de SMN2 sin el modificador genético de SMN2. La supervivencia se define como le elusión de criterios de valoración combinados, ya sea (a) muerte o (b) ventilación permanente, que se define por una traqueostomía o por la necesidad de ≥ 16 horas de asistencia respiratoria al día (mediante asistencia ventilatoria no invasiva) durante ≥ 14 días consecutivos en ausencia de enfermedad reversible aguda, a excepción de la ventilación perioperatoria. La ventilación permanente, según su definición, se considera un desencadenante indirecto de la muerte.
    E.5.2.1Timepoint(s) of evaluation of this end point
    14 months
    14 meses
    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 No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA16
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    Última Visita del Ultimo Paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    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: 30
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Yes
    F.1.1.2.1Number of subjects for this age range: 2
    F.1.1.3Newborns (0-27 days) Yes
    F.1.1.3.1Number of subjects for this age range: 1
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 27
    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.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 30
    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.
    Después de la visita de Fin de Estudio, se propondrá a los pacientes elegibles entrar en el ensayo clinic de seguimiento a largo plazo.
    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 Decision2018-12-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-07-06
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2020-09-11
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