Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1

• Register: ClinicalTrials.gov
• Last refreshed on: 21 June 2021
• Main ID: NCT02122952
• Date of registration: 23/04/2014
• Prospective Registration: Yes
• Primary sponsor: Novartis Gene Therapies
• Public title: Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1
• Scientific title: Phase I Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1 Delivering AVXS-101
• Date of first enrolment: May 5, 2014
• Target sample size: 15
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02122952
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Jerry R Mendell, MD
• Affiliation: The Research Institute at Nationwide Children's Hospital

Key inclusion & exclusion criteria

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.



Age minimum: N/A
Age maximum: 6 Months
Gender: All

Health Condition(s) or Problem(s) studied

Spinal Muscular Atrophy 1

Intervention(s)

Biological: AVXS-101

Primary Outcome(s)

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]

Secondary Outcome(s)

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]

Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) [Time Frame: Baseline and 24 months post-dose]

Secondary ID(s)

AVXS-101-CL-101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 10/05/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02122952