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Trial record 1 of 1 for:    NCT02122952
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Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
AveXis, Inc. Identifier:
First received: April 23, 2014
Last updated: May 24, 2016
Last verified: May 2016
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).

Condition Intervention Phase
Spinal Muscular Atrophy 1
Biological: AVXS-101
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1 Delivering AVXS-101

Resource links provided by NLM:

Further study details as provided by AveXis, Inc.:

Primary Outcome Measures:
  • Safety Outcome Measure assessed by any one Grade III or higher treatment-related toxicity [ Time Frame: 2 years ]

Secondary Outcome Measures:
  • 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 for ≥14 consecutive days in the absence of an acute reversible illness, excluding perioperative use

Enrollment: 15
Study Start Date: April 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
Biological: AVXS-101
Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter
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)
Biological: AVXS-101
Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

Detailed Description:

The study will evaluate safety and efficacy of gene transfer 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 other 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.


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

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.
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Please refer to this study by its identifier: NCT02122952

United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Sponsors and Collaborators
AveXis, Inc.
Principal Investigator: Jerry R Mendell, MD The Research Institute at Nationwide Children's Hospital
  More Information

Additional Information:
Responsible Party: AveXis, Inc. Identifier: NCT02122952     History of Changes
Other Study ID Numbers: AVXS-101-CL-101
Study First Received: April 23, 2014
Last Updated: May 24, 2016

Keywords provided by AveXis, Inc.:
Gene Transfer
Gene Therapy
Adeno-associated virus
Survival Motor Neuron

Additional relevant MeSH terms:
Muscular Atrophy
Muscular Atrophy, Spinal
Spinal Muscular Atrophies of Childhood
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
Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn processed this record on May 25, 2017