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Single-Dose Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1 (STRIVE-EU)

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ClinicalTrials.gov Identifier: NCT03461289
Recruitment Status : Completed
First Posted : March 12, 2018
Last Update Posted : September 23, 2020
Sponsor:
Information provided by (Responsible Party):
AveXis, Inc.

Tracking Information
First Submitted Date  ICMJE March 4, 2018
First Posted Date  ICMJE March 12, 2018
Last Update Posted Date September 23, 2020
Actual Study Start Date  ICMJE August 29, 2018
Actual Primary Completion Date September 11, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 24, 2019)
Sitting without support [ Time Frame: Through 18 months of age ]
Proportion of symptomatic SMA Type 1 patients who are homozygous negative for SMN1 exon 7 and have 2 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
Original Primary Outcome Measures  ICMJE
 (submitted: March 8, 2018)
Sitting without support [ Time Frame: Through 18 months of age ]
Proportion of patients achieving the developmental milestone of sitting without support up to 18 months of age
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2019)
Survival [ Time Frame: Through 14 months of age ]
Survival at 14 months of age amongst symptomatic SMA Type 1 patients who are homozygous negative for SMN1 exon 7 and have 2 copies of SMN2 without the SMN2 genetic modifier
Original Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2018)
Survival [ Time Frame: Through 14 months of age ]
Proportion of patients survivingl at 14 months of age
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Single-Dose Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1
Official Title  ICMJE European, 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
Brief Summary Phase 3, open-label, single-arm, single-dose, trial of onasemnogene abeparvovec-xioi (gene replacement therapy) in patients with spinal muscular atrophy (SMA) Type 1 who meet enrollment criteria and are genetically defined by a biallelic pathogenic mutation of the survival motor neuron 1 gene (SMN1) with one or two copies of survival motor neuron 2 gene (SMN2). Up to 30 patients < 6 months (< 180 days) of age at the time of gene replacement therapy (Day 1) will be enrolled.
Detailed Description

Phase 3, open-label, single-arm, single-dose, trial of onasemnogene abeparvovec-xioi (gene replacement therapy) in patients with spinal muscular atrophy (SMA) Type 1 who meet enrollment criteria and are genetically defined by a biallelic pathogenic mutation of the survival motor neuron 1 gene (SMN1) with one or two copies of survival motor neuron 2 gene (SMN2). 30 patients < 6 months (< 180 days) of age at the time of gene replacement therapy (Day 1) will be enrolled.

The trial includes a screening period, a gene replacement therapy period, and a follow-up period. During the screening period (Days -30 to -2), patients whose parent(s)/legal guardian(s) provide informed consent will complete screening procedures to determine eligibility for trial enrollment. Patients who meet the entry criteria will enter the in-patient gene replacement therapy period (Day -1 to Day 3). On Day -1, patients will be admitted to the hospital for pre-treatment baseline procedures. On Day 1, patients will receive a one-time intravenous (IV) infusion of onasemnogene abeparvovec-xioi, and will undergo in-patient safety monitoring over the next 48 hours. Patients may be discharged 48 hours after the infusion, based on Investigator judgment. During the outpatient follow-up period (Days 4 to End of Trial at 18 months of age), patients will return at regularly scheduled intervals for efficacy and safety assessments until the End of Trial when the patient reaches 18 months of age. After the End of Trial visit, eligible patients will be asked to participate into the long-term follow up trial.

All post-treatment visits will be relative to the date on which gene replacement therapy is administered, until the patient is 14 months of age, after which they will be relevant to the patient's date of birth.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Open-label, single-arm, single-dose, trial of onasemnogene abeparvovec-xioi
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE SMA
Intervention  ICMJE Biological: Onasemnogene Abeparvovec-xioi
Onasemnogene abeparvovec-xioi is a non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the human survival motor neuron (SMN) gene under the control of the cytomegalovirus (CMV) enhancer/chicken β-actin-hybrid promoter (CB).
Study Arms  ICMJE Experimental: Onasemnogene Abeparvovec-xioi
Onasemnogene abeparvovec-xioi is a non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the human survival motor neuron (SMN) gene under the control of the cytomegalovirus (CMV) enhancer/chicken β-actin-hybrid promoter (CB).
Intervention: Biological: Onasemnogene Abeparvovec-xioi
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 24, 2019)
33
Original Estimated Enrollment  ICMJE
 (submitted: March 8, 2018)
30
Actual Study Completion Date  ICMJE September 11, 2020
Actual Primary Completion Date September 11, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with SMA Type 1 as determined by 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 onasemnogene abeparvovec-xioi infusion
  • Patients must have a swallowing evaluation test performed prior to administration of gene replacement therapy

Exclusion Criteria:

  • Previous, planned or expected scoliosis repair surgery/procedure prior to 18 months of age
  • Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry < 95% saturation at screening
  • 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 and unwilling to use an alternative method to oral feeding
  • Participation in recent SMA treatment clinical trial (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 (eg, nusinersen, valproic acid,) at any time prior to screening for this trial.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 6 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Italy,   United Kingdom
Removed Location Countries Germany,   Netherlands,   Spain,   Sweden
 
Administrative Information
NCT Number  ICMJE NCT03461289
Other Study ID Numbers  ICMJE AVXS-101-CL-302
2017-000266-29 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party AveXis, Inc.
Study Sponsor  ICMJE AveXis, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: AveXis Medinfo Sponsor GmbH
PRS Account AveXis, Inc.
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP