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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 : Completed
First Posted : October 11, 2017
Last Update Posted : November 29, 2019
Information provided by (Responsible Party):
AveXis, Inc.

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

Condition or disease Intervention/treatment Phase
SMA - Spinal Muscular Atrophy Gene Therapy Biological: Onasemnogene Abeparvovec-xioi Phase 3

Detailed Description:
Phase 3, open-label, single-arm, single-dose, study 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 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: one-time intravenous administration 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 : October 24, 2017
Actual Primary Completion Date : November 12, 2019
Actual Study Completion Date : November 12, 2019

Arm Intervention/treatment
Experimental: Onasemnogene Abeparvovec-xioi
one-time Intravenous administration of onasemnogene abeparvovec-xioi at the therapeutic dose
Biological: Onasemnogene Abeparvovec-xioi
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 for at least 30 seconds [ 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 ]
    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 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.

Secondary Outcome Measures :
  1. Ability to thrive [ Time Frame: Through 18 months of age ]
    Ability to thrive defined as does not receive nutrition through mechanical support or other non-oral method. Ability to tolerate thin liquids as demonstrated through a formal swallowing test. Maintains weight

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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 as determined by the following features: a. Diagnosis of SMA 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))2
  • The first 3 patients enrolled must meet the criteria for the Intent-To-Treat Population
  • 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
  • Up-to-date on childhood vaccinations. Seasonal vaccinations that include palivizumab prophylaxis (also known as Synagis) to prevent respiratory syncytial virus (RSV) infections are also recommended in accordance with American Academy of Pediatrics (26)
  • Parent(s)/legal guardian(s) willing and able to complete the informed consent process and comply with study procedures and visit schedule

Exclusion Criteria:

  • Previous, planned or expected scoliosis repair surgery/procedure during the study assessment period
  • Pulse oximetry < 96% saturation at screening while the patient is awake or asleep without any supplemental oxygen or respiratory support, or for altitudes > 1000 m, oxygen saturation < 92% awake or asleep without any supplemental oxygen or respiratory support Pulse oximetry saturation may decrease to < 96% after screening provided that the saturation does not decrease by ≥ 4 percentage points
  • 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[25]
  • Active viral infection (includes human immunodeficiency virus [HIV] or positive serology for hepatitis B or C, or Zika virus)
  • Serious non-respiratory tract illness requiring systemic treatment and/or hospitalization within 2 weeks prior to screening
  • Upper or lower respiratory infection requiring medical attention, medical intervention, or increase in supportive care of any manner within 4 weeks prior to screening
  • Severe non-pulmonary/respiratory tract infection within 4 weeks before administration of gene replacement therapy or concomitant illness that creates unnecessary risks for gene replacement therapy such as: a. Major renal or hepatic impairment b. Known seizure disorder c. Diabetes mellitus d. Idiopathic hypocalcuria e. Symptomatic cardiomyopathy
  • Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients
  • Concomitant use of any of the following: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, immunosuppressive therapy within 3 months prior to gene replacement therapy
  • Anti-AAV9 antibody titer > 1:50 as determined by Enzyme-linked Immunosorbent Assay (ELISA) binding immunoassay. Should a potential patient demonstrate Anti-AAV9 antibody titer > 1:50, he or she may receive retesting within 30 days of the screening period and will be eligible to participate if the Anti-AAV9 antibody titer upon retesting is ≤ 1:50
  • Clinically significant abnormal laboratory values (gamma glutamyl- transpeptidase [GGT], ALT, and AST > 3 × ULN, bilirubin ≥ 3.0 mg/dL, creatinine ≥ 1.0 mg/dL, hemoglobin [Hgb] < 8 or > 18 g/dL; white blood cell [WBC] > 20,000 per cmm) prior to gene replacement therapy
  • 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 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 and not a contraindication at any time prior to screening for this study
  • Expectation of major surgical procedures during the study assessment period
  • Parent(s)/legal guardian(s) unable or unwilling to comply with study procedures or inability to travel for repeat visits
  • Parent(s)/legal guardian(s) unwilling to keep study results/observations confidential or to refrain from posting confidential study results/observations on social media sites
  • Parent(s)/legal guardian(s) refuses to sign consent form
  • Gestational age at birth < 35 weeks (245 days)

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

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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:
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Responsible Party: AveXis, Inc. Identifier: NCT03306277    
Other Study ID Numbers: AVXS-101-CL-303
First Posted: October 11, 2017    Key Record Dates
Last Update Posted: November 29, 2019
Last Verified: November 2019
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
Additional relevant MeSH terms:
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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