NCT03461289

Brief Summary

Phase 3, open-label, single-arm, single-dose, trial of onasemnogene abeparvovec-xioi (gene replacement therapy) in patients with spinal muscular atrophy (SMA) Type 1 who meet enrollment criteria and 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). Up to 30 patients \< 6 months (\< 180 days) of age at the time of gene replacement therapy (Day 1) will be enrolled.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
33

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Aug 2018

Geographic Reach
4 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 4, 2018

Completed
8 days until next milestone

First Posted

Study publicly available on registry

March 12, 2018

Completed
5 months until next milestone

Study Start

First participant enrolled

August 16, 2018

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 11, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 11, 2020

Completed
7 months until next milestone

Results Posted

Study results publicly available

April 2, 2021

Completed
Last Updated

January 26, 2026

Status Verified

January 1, 2026

Enrollment Period

2.1 years

First QC Date

March 4, 2018

Results QC Date

March 9, 2021

Last Update Submit

January 7, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • Number of Participants Who Achieve Independent Sitting 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 with head erect for at least 10 seconds; participant does not use arms or hands to balance body or support position.

    From Day 1 up to 18 Months of Age Visit (Up to a Maximum of Approximately 17 Months)

Secondary Outcomes (1)

  • Event-free Survival at 14 Months of Age

    Up to 14 months of age

Study Arms (1)

Onasemnogene Abeparvovec-xioi

EXPERIMENTAL

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).

Biological: Onasemnogene Abeparvovec-xioi

Interventions

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).

Also known as: AVXS-101, OAV101, Zolgensma
Onasemnogene Abeparvovec-xioi

Eligibility Criteria

AgeUp to 6 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Patients 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 two copies of SMN2 \[inclusive of the known SMN2 gene modifier mutation (c.859G\>C)\]
  • Patients must be \< 6 months (\< 180 days) of age at the time of onasemnogene abeparvovec-xioi infusion
  • Patients must have a swallowing evaluation test performed prior to administration of gene replacement therapy

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
  • Use or requirement of non-invasive ventilatory support for 12 or more hours daily in the two weeks prior to dosing
  • Patient 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
  • 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 (eg, nusinersen, valproic acid,) at any time prior to screening for this trial.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

University Hospital Ghent Neuromuscular reference center

Ghent, Belgium

Location

Neuropédiatrie - Centre de Référence des Maladies Neuromusculaires

Liège, Belgium

Location

Hôpital Armand Trousseau

Paris, France

Location

Istituto Gianninia Gaslini

Genova, Italy

Location

Policlinico "G. Martino"

Messina, Italy

Location

Carlo Besta Neurological Research Institute

Milan, Italy

Location

University of Milan

Milan, Italy

Location

Policlinico Gemelli

Rome, Italy

Location

Great Ormond Street Hospital for Children

London, United Kingdom

Location

The John Walton Muscular Dystrophy Research Centre MRC Centre for Neuromuscular Diseases at Newcastle

Newcastle upon Tyne, United Kingdom

Location

Related Publications (2)

  • Mercuri E, Muntoni F, Baranello G, Masson R, Boespflug-Tanguy O, Bruno C, Corti S, Daron A, Deconinck N, Servais L, Straub V, Ouyang H, Chand D, Tauscher-Wisniewski S, Mendonca N, Lavrov A; STR1VE-EU study group. Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy type 1 (STR1VE-EU): an open-label, single-arm, multicentre, phase 3 trial. Lancet Neurol. 2021 Oct;20(10):832-841. doi: 10.1016/S1474-4422(21)00251-9.

  • 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.

Related Links

MeSH Terms

Interventions

Zolgensma

Limitations and Caveats

A comparison of the results from this study to the results from the natural history observational study (Pediatric Neuromuscular Clinical Research Network (PNCR), Finkel et al, 2014) are included in the Novartis Clinical Trial Results, as a historical control. These full results are available via this link: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17805.

Results Point of Contact

Title
EMEA Medical Information
Organization
Novartis Gene Therapies EU Limited

Study Officials

  • AveXis Medinfo

    Sponsor GmbH

    STUDY CHAIR

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
Model Details: Open-label, single-arm, single-dose, trial of onasemnogene abeparvovec-xioi
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 4, 2018

First Posted

March 12, 2018

Study Start

August 16, 2018

Primary Completion

September 11, 2020

Study Completion

September 11, 2020

Last Updated

January 26, 2026

Results First Posted

April 2, 2021

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will share

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

More information

Locations