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   43202   clinical trials with a EudraCT protocol, of which   7150   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

    Download PDF

    Clinical Trial Results:
    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

    Summary
    EudraCT number
    2017-000266-29
    Trial protocol
    GB   FR   SE   BE   ES   NL   IT  
    Global end of trial date
    11 Sep 2020

    Results information
    Results version number
    v3(current)
    This version publication date
    15 May 2022
    First version publication date
    25 Mar 2021
    Other versions
    v1 , v2
    Version creation reason
    • New data added to full data set
    Post Hoc Observational Analysis

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    AVXS-101-CL-302
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03461289
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Study Acronym: STR1VE-EU
    Sponsors
    Sponsor organisation name
    Novartis Gene Therapies, Inc
    Sponsor organisation address
    2275 Half Day Road , Bannockburn, IL , United States, 60015
    Public contact
    EMEA Medical Information, Novartis Gene Therapies EU Limited., +353 (1) 566-2364, medinfoemea.gtx@novartis.com
    Scientific contact
    EMEA Medical Information, Novartis Gene Therapies EU Limited., +353 (1) 566-2364, medinfoemea.gtx@novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-002168-PIP01-17
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    11 Sep 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 Sep 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Sep 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective was to determine efficacy by demonstrating achievement of developmental milestone of sitting without support for at least 10 seconds up to 18 months of age as assessed by World Health Organization (WHO) Motor Developmental Milestones.
    Protection of trial subjects
    The trial was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and was consistent with ICH/GCP, applicable regulatory requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    16 Aug 2018
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Efficacy, Safety
    Long term follow-up duration
    15 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 4
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Italy: 23
    Country: Number of subjects enrolled
    United Kingdom: 4
    Worldwide total number of subjects
    33
    EEA total number of subjects
    29
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    33
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    A total of 33 participants took part in the trial in the United Kingdom, Italy, France and Belgium between August 2018 and September 2020.

    Pre-assignment
    Screening details
    Participants were screened up to 30 days before gene replacement therapy.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Onasemnogene abeparvovec-xioi
    Arm description
    Participants received a single dose of onasemnogene abeparvovec-xioi administered as an intravenous (IV) infusion on Day 1 of the overall study.
    Arm type
    Experimental

    Investigational medicinal product name
    Onasemnogene abeparvovec-xioi
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Onasemnogene abeparvovec-xioi was administered via an IV infusion over 60 minutes at a dose of 1.1 × 10^14 vg/kg (vector genome per kilogram). In order to dampen the host cellular immune response to the AAV-derived therapy, prophylactic prednisolone (or equivalent) was administered 24 hours before and for at least 30 days after dosing.

    Number of subjects in period 1
    Onasemnogene abeparvovec-xioi
    Started
    33
    Completed
    32
    Not completed
    1
         Adverse event, serious fatal
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    -

    Reporting group values
    Overall Study Total
    Number of subjects
    33 33
    Age categorical
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    33 33
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    0 0
        From 65-84 years
    0 0
        85 years and over
    0 0
    Age continuous
    Units: months
        arithmetic mean (standard deviation)
    4.055 ± 1.2799 -
    Gender categorical
    Units: Subjects
        Female
    19 19
        Male
    14 14

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Onasemnogene abeparvovec-xioi
    Reporting group description
    Participants received a single dose of onasemnogene abeparvovec-xioi administered as an intravenous (IV) infusion on Day 1 of the overall study.

    Subject analysis set title
    PNCR (Historical Control)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants in historical control PNCR cohort received uniform standard of care treatment. Participants visited the study site at baseline and at 2, 4, 6, 9, 12 months and every 6 months thereafter.

    Primary: Number of Participants Who Achieve Independent Sitting for at Least 10 Seconds

    Close Top of page
    End point title
    Number of Participants Who Achieve Independent Sitting for at Least 10 Seconds [1]
    End point description
    Independent sitting is defined by the World Health Organization Multicentre Growth Reference Study, confirmed by video recording, as a participant who sits up straight with head erect for at least 10 seconds; participant does not use arms or hands to balance body or support position. The analysis population was the Intent-to-Treat (ITT) population which consisted of symptomatic patients with bi-allelic deletion of SMN1 (exon 7/8 common homozygous deletions) and 2 copies of SMN2 without the known gene modifier mutation (c.859G>C) who received an IV infusion of Onasemnogene abeparvovec-xioi at less than 180 days of age.
    End point type
    Primary
    End point timeframe
    From Study Day 1 up to 18 Months of Age Visit
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No comparative statistical analyses were planned for this endpoint.
    End point values
    Onasemnogene abeparvovec-xioi
    Number of subjects analysed
    32
    Units: Participants
    14
    No statistical analyses for this end point

    Secondary: Event-Free Survival at 14 Months of Age

    Close Top of page
    End point title
    Event-Free Survival at 14 Months of Age
    End point description
    Event-free survival at 14 months of age was defined by avoidance of the combined endpoint of either (a) death or (b) permanent ventilation, defined as requirement of tracheostomy or ≥16 hours of respiratory assistance per day (includes non-invasive ventilatory support) continuously for ≥14 days in the absence of an acute reversible illness, excluding perioperative ventilation. Permanent ventilation, so defined, is considered a surrogate for death.
    End point type
    Secondary
    End point timeframe
    From Study Day 1 up to 14 Months of Age Visit
    End point values
    Onasemnogene abeparvovec-xioi
    Number of subjects analysed
    32
    Units: Participants
    31
    No statistical analyses for this end point

    Other pre-specified: Event-free Survival at 14 Months of Age Compared to Data From an Historical Control, Pediatric Neuromuscular Clinical Research Network (PNCR), Finkel et al, 2014

    Close Top of page
    End point title
    Event-free Survival at 14 Months of Age Compared to Data From an Historical Control, Pediatric Neuromuscular Clinical Research Network (PNCR), Finkel et al, 2014
    End point description
    Data for the current study were compared to data from an historical control (PNCR. Finkel et al, 2014 - PubMed 25080519). Event-free survival at 14 months of age was defined as the number of participants who did not die, did not require permanent ventilation and did not withdraw from the study by 14 months of age. The analysis population for onasemnogene abeparvovec-xioi consisted of symptomatic participants with bi-allelic deletion of SMN1 (exon 7/8 common homozygous deletion), 2 copies of SMN2 without known gene modifier mutation (c.859G>C) who received IV infusion of onasemnogene abeparvovec-xioi at less than 180 days of age. The analysis population for the PNCR study consisted of age of onset ≤ 6 months, biallelic deletion of SMN1 (exon 7/8 common homozygous deletion), 2 copies of SMN2 for whom enrollment data (retrospective and prospective) were available to determine survival.
    End point type
    Other pre-specified
    End point timeframe
    Up to 14 months of age
    End point values
    Onasemnogene abeparvovec-xioi PNCR (Historical Control)
    Number of subjects analysed
    32
    23
    Units: participants
    31
    6
    Statistical analysis title
    Onasemnogene Abeparvovec-xioi vs PNCR
    Comparison groups
    Onasemnogene abeparvovec-xioi v PNCR (Historical Control)
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Fisher exact
    Parameter type
    Difference of Proportion
    Point estimate
    0.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.48
         upper limit
    0.87

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From Day 1 up to 30 days after the 18 months of age visit (up to a maximum of 17 months)
    Adverse event reporting additional description
    Non-serious treatment emergent AEs were collected from Day 1 until 18 months of age visit.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Onasemnogene abeparvovec-xioi
    Reporting group description
    Participants received a single dose of Onasemnogene abeparvovec-xioi administered as an intravenous (IV) infusion on Day 1 of the overall study.

    Serious adverse events
    Onasemnogene abeparvovec-xioi
    Total subjects affected by serious adverse events
         subjects affected / exposed
    19 / 33 (57.58%)
         number of deaths (all causes)
    1
         number of deaths resulting from adverse events
    1
    Surgical and medical procedures
    Gastrostomy
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Hospitalisation
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Coagulation test abnormal
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary function test
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Increased bronchial secretion
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Respiratory failure
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Loss of consciousness
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    4 / 33 (12.12%)
         occurrences causally related to treatment / all
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Dysphagia
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Feeding disorder
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Hypernatraemia
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    5 / 33 (15.15%)
         occurrences causally related to treatment / all
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    3 / 33 (9.09%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    3 / 33 (9.09%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 33 (9.09%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Exanthema subitum
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rhinitis
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Onasemnogene abeparvovec-xioi
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    32 / 33 (96.97%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    4 / 33 (12.12%)
         occurrences all number
    4
    Hypotension
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    2
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    20 / 33 (60.61%)
         occurrences all number
    29
    Crying
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    2
    Extravasation
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Generalised oedema
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Hypothermia
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Necrosis
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Psychiatric disorders
    Irritability
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences all number
    2
    Nervousness
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Psychomotor retardation
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Joint dislocation
         subjects affected / exposed
    3 / 33 (9.09%)
         occurrences all number
    3
    Contusion
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Femur fracture
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    2
    Hand fracture
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Postoperative ileus
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Stoma site haemorrhage
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Vaccination complication
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Stoma site inflammation
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    9 / 33 (27.27%)
         occurrences all number
    11
    Aspartate aminotransferase increased
         subjects affected / exposed
    8 / 33 (24.24%)
         occurrences all number
    9
    Oxygen saturation decreased
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences all number
    2
    Troponin T increased
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences all number
    2
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    2
    Blood creatine phosphokinase MB increased
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Blood phosphorus decreased
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Blood urine present
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Body temperature increased
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Breath sounds
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Haemoglobin decreased
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Haemophilus test positive
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Platelet count increased
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Respiratory syncytial virus test positive
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    2
    Respirovirus test positive
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Staphylococcus test positive
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences all number
    2
    Bradycardia
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    2
    Cyanosis
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    2
    Congenital, familial and genetic disorders
    Cryptorchism
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 33 (18.18%)
         occurrences all number
    7
    Hypoxia
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences all number
    3
    Dyspnoea
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Lung consolidation
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Nasal congestion
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    2
    Respiratory disorder
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Tachypnoea
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Use of accessory respiratory muscles
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Hypersomnia
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Seizure
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Eye disorders
    Strabismus
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Ear and labyrinth disorders
    Tympanic membrane hyperaemia
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    8 / 33 (24.24%)
         occurrences all number
    15
    Constipation
         subjects affected / exposed
    7 / 33 (21.21%)
         occurrences all number
    7
    Diarrhoea
         subjects affected / exposed
    5 / 33 (15.15%)
         occurrences all number
    8
    Gastrooesophageal reflux disease
         subjects affected / exposed
    4 / 33 (12.12%)
         occurrences all number
    4
    Teething
         subjects affected / exposed
    3 / 33 (9.09%)
         occurrences all number
    3
    Salivary hypersecretion
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences all number
    2
    Abdominal pain
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Duodenal ulcer
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Gastritis
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Oral pain
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Renal and urinary disorders
    Leukocyturia
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Hepatobiliary disorders
    Hypertransaminasaemia
         subjects affected / exposed
    8 / 33 (24.24%)
         occurrences all number
    25
    Hepatic steatosis
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Product issues
    Device occlusion
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    3 / 33 (9.09%)
         occurrences all number
    3
    Rash
         subjects affected / exposed
    3 / 33 (9.09%)
         occurrences all number
    3
    Acne infantile
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Dermatitis allergic
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Dermatitis atopic
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Eczema
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Excessive granulation tissue
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Ingrowing nail
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Skin reaction
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Scoliosis
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences all number
    2
    Muscle contracture
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Torticollis
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Failure to thrive
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Feeding disorder
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Hyperphosphatasaemia
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Hypocalcaemia
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Hypomagnesaemia
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    10 / 33 (30.30%)
         occurrences all number
    16
    Nasopharyngitis
         subjects affected / exposed
    4 / 33 (12.12%)
         occurrences all number
    8
    Respiratory tract infection
         subjects affected / exposed
    4 / 33 (12.12%)
         occurrences all number
    4
    Ear infection
         subjects affected / exposed
    3 / 33 (9.09%)
         occurrences all number
    3
    Gastroenteritis
         subjects affected / exposed
    3 / 33 (9.09%)
         occurrences all number
    3
    Candida infection
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences all number
    2
    Impetigo
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences all number
    2
    Pneumonia
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences all number
    2
    Rhinitis
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences all number
    3
    Urinary tract infection
         subjects affected / exposed
    2 / 33 (6.06%)
         occurrences all number
    2
    Bacteriuria
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Bronchitis
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Conjunctivitis
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Cystitis
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Dermatitis infected
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Fungal infection
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    2
    Gastroenteritis viral
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Hordeolum
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Influenza
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Laryngitis
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    2
    Otitis media
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Pharyngitis bacterial
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Roseola
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Urinary tract infection bacterial
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1
    Varicella
         subjects affected / exposed
    1 / 33 (3.03%)
         occurrences all number
    1

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Dec 2017
    The following updates were made: • Addition of cardiac enzyme (CK-MB) monitoring • Added exclusion criterion for patients < 35 weeks gestational age at the time of birth • Updated Phase 1 study results added • Clarified wording related to autopsy and post-mortem tissue/organ collection • Updated until dose terminology based upon improved analytical method (ddPCR) with AveXis GMP product • Revised timepoints for laboratory assessments to allow for blood volume required for CK-MB monitoring • Added length of time for which mother should discontinue breastfeeding in instance of positive antibody titers. • Updated section on saliva, urine, and stool collection to reflect most recent viral shedding data • Minor clarifications and corrections were made to the overall document
    09 Jan 2018
    The following updates were made: • An administrative change to correct a discrepancy in capillary blood gas timepoint.
    04 Oct 2018
    The following updates were made: • Included recent Good Laboratory Practice (GLP) toxicology data • Added benefit/risk language from the Investigator Brochure • Updated onasemnogene abeparvovec-xioi infusion time to 60 minutes from 30-60 minutes. • Added language to allow for prednisolone equivalent • Deleted option for dilution of onasemnogene abeparvovec-xioi with normal saline • Updated schedule and timing of 12-Lead ECGs and echocardiograms • Added 24-hour Holter monitoring • Added Troponin I assessment • Updated immunology testing to remove ELISpot • Adjusted amount of blood volume required for laboratory assessments • Clarified collection of CK-MB and Troponin I relevant to enrollment • Added Pharmacovigilance reporting • Included an additional reference
    17 May 2019
    •Information on, and changes throughout the document as a result of, the acute liver failure case reported in the US Managed Access Program, including: - Update to the prophylactic administration of prednisolone regimen to dampen the immune response to AVXS 101 administration - Risk language updated to include description of recent adverse events and recommendations for liver safety, prolonged monitoring and detailed guidance on tapering of steroid use according to the language from the IB - Participant Exclusion Criterion 12 language updated to include more stringent criteria for liver function tests •Exploratory Objective and Exploratory Endpoint added to provide clarification on evaluation of independent sitting. •Participant Withdrawal Criteria updated to clarify that participants will be offered to continue on the long-term follow-up study. •Clarification provided regarding requirements for reporting elevated liver enzymes and reporting in the Clinical Trial Report. •To include Day 44 and Day 72 visits for blood chemistry, specifically LFTs
    31 Jul 2019
    •Removed exploratory objective and endpoint of ability to sit with support, in order to eliminate Bayley III item 19 which is not a defined milestone for this study •Clarified that 30 eligible participants were planned to be enrolled, but that patients who were already in screening at the time this enrollment target was met who met eligibility criteria could enroll upon approval of AveXis; this was so as to acknowledge that the number of participants may slightly exceed the enrollment target in this competitive enrolment trial •Added statement that patients who discontinue this trial prematurely will be invited to participate in the long-term follow up study •Updated description of the timing of post-treatment visits to be relative to date of gene therapy until the patient is 14 months of age (14 month of age visit), after which visits are to be relative to the patient’s date of birth •Head circumference measurement was added to Physical Examination in order to align with the physical examination case report form •Removed statement that biological mothers who test positive for antibodies to AAV9 will be asked to refrain from breast feeding until at least 1 month after AVXS-101 dose
    26 Nov 2019
    The following updates were made: • Removal of Safety Objective to determine the safety of onasemnogene abeparvovec-xioi based on the development of unacceptable toxicity • Amended description of the role of the DSMB/DMC, timing and schedule of reviews, and recommendations and notification to regulatory authorities, as described in the DSMB/DMC Charter • Revised safety endpoints and analysis description • Risk language updated to include description of non-human primate (NHP) intrathecal study findings and the potential risk of neuronal toxicity following IT administration of onasemnogene abeparvovec-xioi • Detailed and age appropriate sensory testing added to be performed at each visit and any clinically significant abnormal finding recorded as an adverse event • Non-invasive ventilatory support usage recorded in the electronic Case Report Form (eCRF) to assist with identification of survival endpoints • All adverse events that occur after signing the informed consent through to the last trial visit collected and recorded in the eCRF • All SAEs (related and unrelated) recorded after signing of the consent form through 30 days after the last study visit • Trial enrolment not interrupted should any patient experience an unanticipated Grade 3 or higher related adverse event, pending DSMB/DMC review • Unanticipated Grade 3 or higher related adverse events will not be reported within 24 hours, unless they are adverse events of special interest (AESIs) or serious adverse events (SAEs) • AESIs, such as hepatotoxicity, thrombocytopenia, cardiac adverse events and sensory abnormalities potentially due to dorsal root ganglia inflammation are included/defined and the reporting requirements clarified • Elective procedures or minor surgeries where hospitalisation is required, should not be reported as SAE • Updated schedule of assessments and references.
    25 Jun 2020
    The following updates were made: • Insertion of new language to address the impact of COVID-19 on trial conduct • Key Contact Information and additional study contact information updated as part of administrative changes • Addition of abbreviations and definitions of terms • Application of consistent definition of primary endpoint and exploratory endpoints • Clarification of the collection and central review of videos of efficacy parameters • Insertion of specific safety reporting requirements of the French Competent Authority • Insertion of Hy’s Law Criteria • Clarification and correction of statistical analysis definitions

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    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 © 1995-2023 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA