Pre-Symptomatic Study of Intravenous Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2

NCT03505099 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: AVXS-101-CL-3042017-004087-35JapicCTI-184203COAV101A12303
• Study Type: interventional
• Target: 30
• Locations: 6 countries
• Sites: 16

Brief Summary

To evaluate the safety and efficacy of intravenous onasemnogene abeparvovec-xioi in pre-symptomatic patients with SMA and 2 or 3 copies SMN2

Conditions

Spinal Muscular Atrophy

Keywords

gene therapy

Outcome Measures

Primary Outcomes (2)

• Cohort 1: Number of Participants Who Achieved Sitting Alone for at Least 30 Seconds

  Defined by the Bayley Scales of Infant and Toddler Development (BSID) Gross Motor (GM) subtest performance criteria number 26, confirmed by video recording, as a participant who sits for at least 30 seconds without assistance from another person or object. The participant was allowed to use their upper extremities.

  From Day 1 up to 18 months of age visit

• Cohort 2: Number of Participants Who Achieved Standing Alone for at Least 3 Seconds

  Defined by the BSID GM subtest performance criteria number 40, confirmed by video recording, as a participant who stands alone for at least 3 seconds unsupported.

  From Day 1 up to 24 months of age visit

Secondary Outcomes (3)

• Cohort 1: Event-free Survival at 14 Months of Age

  From Day 1 up to 14 months of age

• Cohort 1: Number of Participants Who Achieved the Ability to Maintain Weight at or Above the Third Percentile Without the Need for Non-Oral or Mechanical Feeding Support

  From Day 1 up to 18 months of age

• Cohort 2: Number of Participants Who Achieved the Ability to Walk Alone

  From Day 1 up to 24 months of age visit

Study Arms (1)

onasemnogene abeparvovec-xioi

EXPERIMENTAL

One-time intravenous infusion of onasemnogene abeparvovec-xioi at 1.1 X 10\^14 vg/kg

Biological: onasemnogene abeparvovec-xioi

Interventions

onasemnogene abeparvovec-xioi BIOLOGICAL

A non-replicating recombinant AAV9 containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.

Also known as: Zolgensma

onasemnogene abeparvovec-xioi

Eligibility Criteria

• Age: Up to 42 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age ≤6 weeks (≤42 days) at time of dose
• Ability to tolerate thin liquids as demonstrated through a formal bedside swallowing test
• Compound muscle action potential (CMAP) ≥2mV at Baseline; centralized review of CMAP data will be conducted
• Gestational age of 35 to 42 weeks
• Parent(s)/legal guardian(s) willing and able to complete the informed consent process and comply with study procedures and visit schedule
• Patients with pre-symptomatic SMA Type 1 as determined by the following features:
• a. 2 copies of SMN2 (n ≥14)
• Patients with pre-symptomatic SMA Type 2 as determined by the following features:
• copies of SMN2 (n ≥12)

You may not qualify if:

• Weight at screening visit \<2 kg
• Hypoxemia (oxygen saturation \<96% awake or asleep without any supplemental oxygen or respiratory support) at the screening visit or for altitudes \>1000 m, oxygen saturation \<92% awake or asleep without any supplemental oxygen or respiratory support at the screening visit
• Any clinical signs or symptoms at screening or immediately prior to dosing that are, in the opinion of the Investigator, strongly suggestive of SMA
• Tracheostomy or current prophylactic use or requirement of noninvasive ventilatory support at any time and for any duration prior to screening or during the screening period
• Patients with signs of aspiration/inability to tolerate nonthickened liquids based on a formal swallowing test performed as part of screening or patients receiving any non-oral feeding method
• Clinically significant abnormal laboratory values (gamma-glutamyl transferase \[GGT\], Alanine transaminase \[ALT\], and aspartate aminotransferase \[AST\], or total bilirubin \> 2 × the upper limit of normal \[ULN\], creatinine ≥ 1.0 mg/dL, hemoglobin \[Hgb\] \< 8 or \> 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
• Treatment with an investigational or commercial product, including nusinersen, given for the treatment of SMA. This includes any history of gene therapy, prior antisense oligonucleotide treatment, or cell transplantation.
• Patients whose weight-for-age is below the third percentile based on World Health Organization (WHO) Child Growth Standards
• Biological mother with active viral infection as determined by screening laboratory samples (includes human immunodeficiency virus \[HIV\] or positive serology for hepatitis B or C)
• Biological mothers with clinical suspicion of Zika virus that meet Centers for Disease Control and Prevention (CDC) Zika virus epidemiological criteria including history of residence in or travel to a geographic region with active Zika transmission at the time of travel will be tested for Zika virus RNA. Positive results warrant confirmed negative Zika virus RNA testing in the patient prior to enrollment.
• Serious nonrespiratory 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 dosing
• Severe nonpulmonary/respiratory tract infection within 4 Weeks before administration of gene replacement therapy or concomitant illness that, in the opinion of the Investigator or Sponsor medical monitor, creates unnecessary risks for gene replacement therapy such as:
• Major renal or hepatic impairment
• Known seizure disorder

Sponsors & Collaborators

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

Study Sites (16)

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Nemours Children's Hospital

Orlando, Florida, 32827, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Clinic for Special Children

Strasburg, Pennsylvania, 17579, United States

Location

Children's Medical Center Dallas

Dallas, Texas, 75235, United States

Location

University Hospital and UW Health Clinics

Madison, Wisconsin, 53792, United States

Location

Sydney Children's Hospital

Randwick, New South Wales, 2145, Australia

Location

Centre Hospitalier Régional Hôpital La Citadelle

Liège, 4000, Belgium

Location

Canada Childrens Hospital of Eastern Ontario

Ottawa, Ontario, K1H8L1, Canada

Location

Tokyo Women's Medical

Tokyo, Japan

Location

Great Ormond Street Hospital for Children NHS Foundation Trust

London, WC1N 3JH, United Kingdom

Location

Related Publications (3)

• Strauss KA, Farrar MA, Muntoni F, Saito K, Mendell JR, Servais L, McMillan HJ, Finkel RS, Swoboda KJ, Kwon JM, Zaidman CM, Chiriboga CA, Iannaccone ST, Krueger JM, Parsons JA, Shieh PB, Kavanagh S, Wigderson M, Tauscher-Wisniewski S, McGill BE, Macek TA. Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial. Nat Med. 2022 Jul;28(7):1390-1397. doi: 10.1038/s41591-022-01867-3. Epub 2022 Jun 17.

  PMID: 35715567 DERIVED

• Strauss KA, Farrar MA, Muntoni F, Saito K, Mendell JR, Servais L, McMillan HJ, Finkel RS, Swoboda KJ, Kwon JM, Zaidman CM, Chiriboga CA, Iannaccone ST, Krueger JM, Parsons JA, Shieh PB, Kavanagh S, Tauscher-Wisniewski S, McGill BE, Macek TA. Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial. Nat Med. 2022 Jul;28(7):1381-1389. doi: 10.1038/s41591-022-01866-4. Epub 2022 Jun 17.

  PMID: 35715566 DERIVED

• 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

Muscular Atrophy, Spinal

Interventions

Zolgensma

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Limitations and Caveats

Link to the full study results: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17902

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

Model Details: Open-label, single arm

Study Record Dates

• First Submitted: April 13, 2018
• First Posted: April 23, 2018
• Study Start: April 2, 2018
• Primary Completion: June 15, 2021
• Study Completion: June 15, 2021
• Last Updated: January 26, 2026
• Results First Posted: January 11, 2022

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

BE (1); GB (1); CA (1); AU (1); US (11); JP (1)