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

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ClinicalTrials.gov Identifier: NCT03461289
Recruitment Status : Completed
First Posted : March 12, 2018
Results First Posted : April 2, 2021
Last Update Posted : April 14, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Gene Therapies )

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.

Condition or disease Intervention/treatment Phase
SMA Biological: Onasemnogene Abeparvovec-xioi Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
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
Official Title: 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
Actual Study Start Date : August 16, 2018
Actual Primary Completion Date : September 11, 2020
Actual Study Completion Date : September 11, 2020


Arm Intervention/treatment
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).
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).
Other Names:
  • AVXS-101
  • OAV101
  • Zolgensma




Primary Outcome Measures :
  1. Number of Participants Who Achieve Independent Sitting for at Least 10 Seconds [ Time Frame: From Day 1 up to 18 Months of Age Visit (Up to a Maximum of Approximately 17 Months) ]
    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.


Secondary Outcome Measures :
  1. Event-Free Survival at 14 Months of Age [ Time Frame: From Study Day 1 up to 14 Months of Age Visit ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 6 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03461289


Locations
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Belgium
University Hospital Ghent Neuromuscular reference center
Ghent, Belgium
Neuropédiatrie - Centre de Référence des Maladies Neuromusculaires
Liège, Belgium
France
Hôpital Armand Trousseau
Paris, France
Italy
Istituto Gianninia Gaslini
Genova, Italy
Policlinico "G. Martino"
Messina, Italy
Carlo Besta Neurological Research Institute
Milan, Italy
University of Milan
Milan, Italy
Policlinico Gemelli
Rome, Italy
United Kingdom
Great Ormond Street Hospital for Children
London, United Kingdom
The John Walton Muscular Dystrophy Research Centre MRC Centre for Neuromuscular Diseases at Newcastle
Newcastle Upon Tyne, United Kingdom
Sponsors and Collaborators
Novartis Gene Therapies
Investigators
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Study Chair: AveXis Medinfo Sponsor GmbH
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Gene Therapies ):
Study Protocol  [PDF] June 25, 2020
Statistical Analysis Plan  [PDF] November 3, 2020

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Gene Therapies
ClinicalTrials.gov Identifier: NCT03461289    
Other Study ID Numbers: AVXS-101-CL-302
2017-000266-29 ( EudraCT Number )
First Posted: March 12, 2018    Key Record Dates
Results First Posted: April 2, 2021
Last Update Posted: April 14, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Muscular Atrophy
Muscular Atrophy, Spinal
Atrophy
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases