Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1 (STR1VE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03306277
Recruitment Status : Active, not recruiting
First Posted : October 11, 2017
Last Update Posted : October 11, 2018
Information provided by (Responsible Party):
AveXis, Inc.

Brief Summary:
Phase 3 pivotal US trial studying open-label intravenous administration of AVXS-101 in SMA Type 1 patients

Condition or disease Intervention/treatment Phase
SMA - Spinal Muscular Atrophy Gene Therapy Biological: AVXS-101 Phase 3

Detailed Description:
Phase 3, open-label, single-arm, single-dose, study of AVXS-101 (gene replacement therapy) in patients with spinal muscular atrophy (SMA) Type 1 who meet enrollment criteria and are genetically defined by nonfunctional survival motor neuron 1 gene (SMN1) with 1 or 2 copies of survival motor neuron 2 gene (SMN2). Fifteen (15) patients < 6 months (< 180 days) of age at the time of gene replacement therapy (Day 1) will be enrolled.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Intervention Model Description: one-time intravenous administration of AVXS-101
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 : September 29, 2017
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : March 31, 2020

Arm Intervention/treatment
Experimental: AVXS-101
one-time Intravenous administration of AVXS-101 at the therapeutic dose
Biological: AVXS-101
Non-replicating recombinant AAV9 containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.

Primary Outcome Measures :
  1. Achievement of independent sitting [ Time Frame: 18 months of age visit ]
    Achievement of developmental milestone of independent sitting at 18 months of age

  2. Event-free survival [ Time Frame: 14 months of age visit ]
    Event-free survival at 14 months of age.

Secondary Outcome Measures :
  1. Ability to thrive [ Time Frame: Through 18 months of age ]
    Determine effect of AVXS-101 on the ability to thrive.

  2. Ventilatory support independence [ Time Frame: Through 18 months of age ]
    Determine the effect of AVXS-101 on the ability to remain independent of ventilatory support

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 180 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with SMA Type 1 based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and 1 or 2 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

Exclusion Criteria:

  • Tracheostomy or current use or requirement of non-invasive ventilatory support averaging ≥ 6 hours daily over the 7 days prior to the screening visit; or ≥ 6 hours/day on average during the screening period or requiring ventilatory support while awake over the 7 days prior to screening or at any point during the screening period prior to dosing
  • Patients with signs of aspiration/inability to tolerate non-thickened liquids based on a formal swallowing test performed as part of screening. Patients with a gastrostomy tube who pass the swallowing test will be allowed to enroll in the study
  • Patients whose weight-for-age is below the third percentile based on World Health Organization (WHO) Child Growth Standards
  • 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

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 identifier (NCT number): NCT03306277

United States, California
David Geffen School of Medicine at UCLA
Los Angeles, California, United States, 90095
Stanford University
Stanford, California, United States, 94305
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Nemours Children's Hospital
Orlando, Florida, United States, 32827
United States, Illinois
Ann and Robert H Lurie Children's Hospital
Chicago, Illinois, United States, 60611
United States, Maryland
Johns Hopkins Pediatric Neurology
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington Unviersity School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Columbia University
New York, New York, United States, 10032
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27713
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75235
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
United States, Wisconsin
University of Wisconsin (Madison)
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
AveXis, Inc.

Additional Information:
Responsible Party: AveXis, Inc. Identifier: NCT03306277     History of Changes
Other Study ID Numbers: AVXS-101-CL-303
First Posted: October 11, 2017    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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