Phase 3
N=2
Single-Dose Gene Replacement Therapy Using for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies
Spinal Muscular Atrophy Type I
Bottom Line
View on ClinicalTrials.gov: NCT03837184 ↗Enrolled (actual)
2
Serious AEs
50.0%
Results posted
Jan 2022
Primary outcome: Primary: Number of Participants Who Achieved Sitting Alone for at Least 10 Seconds — 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Onasemnogene Abeparvovec-xioi (Biological)
- Age
- Pediatric · 0+ yrs
- Sex
- All
- Sponsor
- Novartis Gene Therapies
- Primary completion
- Jun 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Achieved Sitting Alone for at Least 10 Seconds |
1 | — |
| SECONDARY Event-free Survival at 14 Months of Age |
2 | — |
Summary
This is a Phase 3, open-label, single-arm, single-dose, trial of onasemnogene abeparvovec-xioi (gene replacement therapy) in participants with spinal muscular atrophy (SMA) Type 1 and who are genetically defined by a biallelic pathogenic mutation of the survival motor neuron 1 gene (SMN1) with one or two copies of survival motor neuron 2 gene (SMN2). The primary objective of the study is to evaluate the efficacy of onasemnogene abeparvovec-xioi by assessing the proportion of symptomatic SMA Type 1 participants who achieve the ability to sit unaided for at least 10 seconds up to and including the 18 months of age trial visit. At least 6 participants aged < 6 months (< 180 days) at the time of gene replacement therapy (Day 1) will be enrolled.
Eligibility Criteria
Inclusion Criteria
- Participants with SMA Type 1 as determined by diagnosis of SMA based on gene mutation analysis with biallelic SMN1 mutations (deletion or point mutations) and one or 2 copies of SMN2 [inclusive of the known SMN2 gene modifier mutation (c.859G>C)]
- Participants must be 1: 50 as determined by Enzyme-linked Immunosorbent Assay (ELISA) binding immunoassay. Should a potential participant 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, AST, total bilirubin > 2x the ULN, creatinine ≥ 1.0 mg/dL, hemoglobin [Hgb] 18 g/dL; white blood cell [WBC] > 20,000 per cmm) prior to gene replacement therapy. Patients with an elevated bilirubin level that is unequivocally the result of neonatal jaundice shall not be excluded
- Participation in recent SMA treatment clinical trial (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 trial. Oral beta-agonists must be discontinued at least 30 days prior to 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 trial
- Expectation of major surgical procedures during the trial assessment period (e.g., spinal surgery or tracheostomy)
- Parent(s)/legal guardian(s) unable or unwilling to comply with trial procedures or inability to travel for repeat visits
- Parent(s)/legal guardian(s) unwilling to keep trial results/observations confidential or to refrain from posting confidential trial results/observations on social media sites
- Parent(s)/legal guardian(s) refuses to sign consent form
- Participants < 35 weeks gestational age at time of birth
Data sourced from ClinicalTrials.gov (NCT03837184). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.