Single-Dose Gene Replacement Therapy Using for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies

NCT03837184 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: AVXS-101-CL-306194664201900208COAV101A12304
• Study Type: interventional
• Target: 2
• Locations: 3 countries
• Sites: 4

Brief 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.

Conditions

Spinal Muscular Atrophy Type I

Keywords

Spinal Muscular Atrophy; SMN2; Onasemnogene Abeparvovec-xioi; Gene replacement therapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Achieved Sitting Alone for at Least 10 Seconds

  Independent sitting is defined by the World Health Organization Multicentre Growth Reference Study, confirmed by video recording, as a participant who sits up straight unsupported for at least 10 seconds.

  From Baseline up to 18 Months of Age Visit

Secondary Outcomes (1)

• Event-free Survival at 14 Months of Age

  From Baseline up to 14 Months of Age

Study Arms (1)

Onasemnogene Abeparvovec-xioi

EXPERIMENTAL

Participants will receive a single dose of onasemnogene abeparvovec-xioi, administered intravenously.

Biological: Onasemnogene Abeparvovec-xioi

Interventions

Onasemnogene Abeparvovec-xioi BIOLOGICAL

Onasemnogene abeparvovec-xioi is a non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the human survival motor neuron (SMN) gene under the control of the cytomegalovirus (CMV) enhancer/chicken β-actin-hybrid promoter (CB). Onasemnogene abeparvovec-xioi will be administered as a one-time intravenous infusion over approximately 60 minutes. Dosage will be determined by the participants weight.

Also known as: Zolgensma

Onasemnogene Abeparvovec-xioi

Eligibility Criteria

• Age: 0 Days - 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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 \< 6 months (\< 180 days) of age at the time of onasemnogene abeparvovec-xioi infusion
• Participants must have a swallowing evaluation test performed prior to administration of gene replacement therapy
• Up-to-date on childhood vaccinations as per local health authorities.
• Parent(s)/legal guardian(s) willing and able to complete the informed consent process and comply with trial procedures and visit schedule

You may not qualify if:

• Previous, planned or expected scoliosis repair surgery/procedure prior to 18 months of age
• Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry \< 95% saturation at screening:
• Pulse oximetry saturation must not decrease ≥ 4 percentage points between screening and dosing with confirmatory oximetry reading
• Participants may be put on non-invasive ventilatory support for less than 12 hours per day at the discretion of their physician or trial staff
• Use or requirement of non-invasive ventilatory support for greater than or equal to 12 hours daily in the two weeks prior to dosing
• Participant with signs of aspiration based on a swallowing test or whose weight-for-age falls below the 3rd percentile based on World Health Organization (WHO) Child Growth Standards and unwilling to use an alternative method to oral feeding
• Active viral infection (includes human immunodeficiency virus \[HIV\] or positive serology for hepatitis B, C, or E, or known Zika virus infection)
• 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 (eg, pyelonephritis, or meningitis) within 4 weeks before administration of gene replacement therapy or concomitant illness that, in the opinion of the Principal Investigator, creates unnecessary risks for gene replacement such as:
• Major renal or hepatic impairment
• Known seizure disorder
• Diabetes mellitus
• Idiopathic hypocalcuria
• Symptomatic cardiomyopathy

Sponsors & Collaborators

• Novartis Gene Therapies: lead
• PRA Health Sciences: collaborator

Study Sites (4)

Tokyo Women's Medical University

Tokyo, Japan

Location

Pusan National University Yangsan Hospital

Yangsan, Gyeongsangnam-do, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Related Publications (1)

• Day JW, Mendell JR, Mercuri E, Finkel RS, Strauss KA, Kleyn A, Tauscher-Wisniewski S, Tukov FF, Reyna SP, Chand DH. Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy. Drug Saf. 2021 Oct;44(10):1109-1119. doi: 10.1007/s40264-021-01107-6. Epub 2021 Aug 12.

  PMID: 34383289 DERIVED

Related Links

• Novartis Clinical Trial Results
• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Spinal Muscular Atrophies of Childhood; Muscular Atrophy, Spinal

Interventions

Zolgensma

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: EMEA Medical Information
• Organization: Novartis Gene Therapies EU Limited

medinfoemea.gtx@novartis.com

+353 (1) 566-2364

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: February 12, 2019
• Study Start: May 31, 2019
• Primary Completion: June 29, 2021
• Study Completion: June 29, 2021
• Last Updated: January 26, 2026
• Results First Posted: January 11, 2022

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

TW (1); JP (1); KR (2)