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Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1

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: NCT02122952
Recruitment Status : Completed
First Posted : April 25, 2014
Results First Posted : May 10, 2019
Last Update Posted : June 14, 2021
Information provided by (Responsible Party):
Novartis ( Novartis Gene Therapies )

Tracking Information
First Submitted Date  ICMJE April 23, 2014
First Posted Date  ICMJE April 25, 2014
Results First Submitted Date  ICMJE July 20, 2018
Results First Posted Date  ICMJE May 10, 2019
Last Update Posted Date June 14, 2021
Actual Study Start Date  ICMJE May 5, 2014
Actual Primary Completion Date December 15, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2019)
Number of Participants That Experienced One Grade III or Higher Unanticipated, Treatment-related Toxicity That Presents With Clinical Symptoms and Requires Medical Treatment [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 23, 2014)
Safety Outcome Measure [ Time Frame: 2 years ]
Any one Grade III or higher treatment-related toxicity
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2019)
  • Number of Participants Who Experienced (a) Requirement of ≥16-hour Respiratory Assistance Per Day Continuously for ≥2 Weeks in the Absence of an Acute Reversible Illness, Excluding Perioperative Ventilation, or (b) Death [ Time Frame: 24 months post-dose ]
    Respiratory assistance included non-invasive ventilatory support.
  • Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) [ Time Frame: Baseline and 24 months post-dose ]
    CHOP-INTEND scores at baseline and 24 months post-dose. Scores = 0-64, where 64 is the maximum possible score. A higher score is indicative of higher/better motor function.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2014)
  • Mortality [ Time Frame: 2 years ]
    Time from birth to time of death
  • Time-to-Event Outcome Measure [ Time Frame: 2 years ]
    Time from birth to medically prescribed respiratory assistance required 16 hours per day or more.
Current Other Pre-specified Outcome Measures
 (submitted: February 8, 2019)
Number of Participants With Assessed Improvement in Motor Function [ Time Frame: 24 months post-dose ]
Improvement in motor function was determined by achievement of developmental milestones, specifically achievement of ability to sit unassisted for at least 30 seconds, determined by physical therapist and confirmed by an independent central video reviewer. Achievement of functional independent sitting was defined as the ability to maintain a sitting position independently for at least 30 seconds as confirmed per video evaluation by an expert central reviewer based on videos taken either at scheduled visits or provided by the parent/legal guardian.
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1
Official Title  ICMJE Phase I Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1 Delivering AVXS-101
Brief Summary The purpose of this trial is to evaluate safety and efficacy of intravenous delivery of AVXS-101 as a treatment of spinal muscular atrophy Type 1 (SMN1).
Detailed Description

The study will evaluate safety and efficacy of gene therapy in spinal muscular atrophy Type 1 (SMA1) patients. SMA is caused by low levels of the survival motor neuron (SMN) protein, and affects all muscles in the body. There is no effective treatment for SMA and current drug therapy has been unsuccessful in stabilizing or reversing this disease. Only supportive care is currently possible.

Open-label, dose-escalation clinical trial of AVXS-101 injected intravenously through a peripheral limb vein. Short-term safety will be evaluated over a two year period. Patients will be tested at baseline and return for follow up visits on days 7, 14, 21, 30, followed by once every month through 12 months post dose, and then every three months through two (2) years post infusion. Unscheduled visits may occur if the PI determines that they are necessary.

The primary analysis for efficacy will be assessed when all patients reach 13.6 months of age (a database lock will be performed at the time point at which all patients reach 13.6 months of age). A follow-up safety analysis will be completed at the time point at which the last patient reaches 24 months post-dose.

Upon completion of the 2-year study period, patients will be monitored annually as per standard of care for up to 15 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Spinal Muscular Atrophy 1
Intervention  ICMJE Biological: AVXS-101
Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter
Other Name: Zolgensma
Study Arms  ICMJE
  • Experimental: Cohort 1
    6.7 X 10^13 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=3)
    Intervention: Biological: AVXS-101
  • Experimental: Cohort 2
    2.0 X 10^14 vg/kg of AVXS-101 delivered one-time through a venous catheter inserted into a peripheral vein (n=12)
    Intervention: Biological: AVXS-101
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 6, 2015)
Original Estimated Enrollment  ICMJE
 (submitted: April 23, 2014)
Actual Study Completion Date  ICMJE December 15, 2017
Actual Primary Completion Date December 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Six or nine months of age and younger (depending on cohort) on day of vector infusion with Type 1 SMA as defined by the following features:

    • Diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and 2 copies of SMN2.
    • Onset of disease at birth up to 6 months of age.
    • Hypotonia by clinical evaluation with delay in motor skills, poor head control, round shoulder posture and hypermobility of joints.

Exclusion Criteria:

  • Active viral infection (includes HIV or serology positive for hepatitis B or C)
  • Use of invasive ventilatory support (tracheotomy with positive pressure)* or pulse oximetry <95% saturation.
  • Patients may be put on non-invasive ventilator support (BiPAP) for less than 16 hours a day at the discretion of their physician or research staff.
  • Concomitant illness that in the opinion of the PI creates unnecessary risks for gene transfer
  • Concomitant use of any of the following drugs: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy or immunosuppressive therapy within 3 months of starting the trial (e.g. corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab)
  • Patients with Anti-AAV9 antibody titers >1:50 as determined by ELISA binding immunoassay.
  • Abnormal laboratory values considered clinically significant (GGT > 3XULN, bilirubin ≥ 3.0 mg/dL , creatinine ≥ 1.8 mg/dL, Hgb < 8 or > 18 g/Dl; WBC > 20,000 per cmm) Participation in a recent SMA treatment clinical trial that in the opinion of the PI creates unnecessary risks for gene transfer.
  • Family does not want to disclose patient's study participation with primary care physician and other medical providers.
  • Patient with signs of aspiration based on a swallowing test and unwilling to use an alternative method to oral feeding.
  • Patients with a single base substitution in SMN2 (c.859G>C in exon 7) will be excluded based on predicted mild phenotype.
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 United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02122952
Other Study ID Numbers  ICMJE AVXS-101-CL-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Gene Therapies )
Study Sponsor  ICMJE Novartis Gene Therapies
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jerry R Mendell, MD The Research Institute at Nationwide Children's Hospital
PRS Account Novartis
Verification Date June 2021

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