Efficacy and Safety of Intrathecal OAV101 (AVXS-101) in Pediatric Patients With Type 2 Spinal Muscular Atrophy (SMA)

Last updated: November 20, 2025
Sponsor: Novartis Pharmaceuticals
Overall Status: Completed

Phase

3

Condition

Muscular Dystrophy

Myasthenia Gravis (Chronic Weakness)

Spinal Muscular Atrophy

Treatment

OAV101

Sham control

Clinical Study ID

NCT05089656
COAV101B12301
2021-003474-31
  • Ages 2-17
  • All Genders

Study Summary

This was a Phase III multi-center, single dose (1.2 x 10^14 vector genomes), randomized, sham controlled, double-blind study that investigates the efficacy, safety and tolerability of OAV101B in treatment naive, sitting and never ambulatory SMA patients 2 to <18 years of age.

Eligibility Criteria

Inclusion

Key Inclusion criteria:

  • Diagnostic confirmation during screening period of 5q SMA

  • The patient must be treatment naive (historical or current use) for allSMN-targeting therapies (e.g., risdiplam (Evrysdi) and nusinersen (Spinraza)).

  • Onset of clinical signs and symptoms at ≥ 6 months of age

  • A complete Hammersmith Functional Motor Scale - Expanded (HFMSE) assessment duringthe screening period for trial eligibility

  • Able to sit independently at screening, but has never had the ability to walkindependently.

Exclusion

Key Exclusion criteria:

  • Anti-adeno-associated virus serotype 9 (AAV9) antibody titer reported as elevated (reference to > 1:50 or validated result consistent with being elevated) atscreening as determined by sponsor designated lab.

  • Infectious process (e.g., viral, bacterial) or febrile illness within 30 days priorto OAV101 treatment or sham procedure

  • Hepatic dysfunction (i.e. alanine aminotransferase (ALT), total bilirubin,gamma-glutamyl transferase (GGT) or glutamate dehydrogenase (GLDH), > upper limit ofnormal (ULN).

  • Requiring invasive ventilation, awake noninvasive ventilation for > 6 hours during a 24-hour period, noninvasive ventilation for > 12 hours during a 24-hour period orrequiring tracheostomy

  • Complications at screening that would interfere with motor efficacy assessmentsincluding but not limited to, severe contractures or Cobb angle > 40 in a sittingposition

  • Surgery for scoliosis or hip fixation in the 12 months prior to Screening or plannedwithin the next 64 weeks

  • Clinically significant sensory abnormalities in the neurological examination atScreening

Study Design

Total Participants: 126
Treatment Group(s): 2
Primary Treatment: OAV101
Phase: 3
Study Start date:
February 01, 2022
Estimated Completion Date:
April 29, 2025

Study Description

Eligible participants received a single administration of OAV101B at the dose of 1.2 x 10^14 vector genomes intrathecally or the sham procedure on Day 1 (Treatment Period 1), and were followed for a period of 52 weeks for Period 1. In Period 2, participants who received the sham treatment in Period 1 were administered OAV101B, and participants who received OAV101B in Period 1 underwent the sham procedure. Participants were followed up for 12 weeks in Period 2.

The study consisted of a Screening and Baseline Period followed by two Treatment and Follow-up Periods. Participants were admitted to the hospital on Day 1 (or Day -1 as per local standards of care). After receiving OAV101B or the sham procedure on Day 1, participants underwent in-patient safety monitoring through Day 2 and optionally for Day 3.

After Period 1, eligible participants could continue to Period 2 subsequently entering Period 2 in a rolling seamless fashion as participants completed Follow-up Period 1. In Treatment Period 2, eligible participants who received a sham procedure on Study Day 1 of Treatment Period 1 were hospitalized to receive OAV101B on Week 52 + 1 day and participants who received OAV101B on Study Day 1 of Treatment Period 1 were hospitalized to receive a sham procedure on the Week 52 + 1 Day. The total duration of the study including both Period 1 and Period 2 was 64 weeks. At the end of the study, all participants who received OAV101B were eligible to enroll in a long-term follow-up study to monitor long-term safety and efficacy.

Approximately 125 participants were planned to be randomized in a 3:2 ratio to receive OAV101B (N= ~75) or a sham procedure (N= ~50). The unequal randomization ratio allowed more participants to receive active treatment in Period 1. It was anticipated that approximately 65 randomized participants would be aged 2 to <5 years and approximately 60 randomized participants would be aged 5 to <18 years.

Connect with a study center

  • Novartis Investigative Site

    Curitiba, PR 81520-060
    Brazil

    Site Not Available

  • Novartis Investigative Site

    Curitiba 3464975, Paraná 3455077 81520-060
    Brazil

    Site Not Available

  • Novartis Investigative Site

    Porto Alegre, RS 90035-903
    Brazil

    Site Not Available

  • Novartis Investigative Site

    Campinas, SP 13083-970
    Brazil

    Site Not Available

  • Novartis Investigative Site

    Sao Paulo, SP 05403 000
    Brazil

    Site Not Available

  • Novartis Investigative Site

    São Paulo 3448439, São Paulo 3448433 05403 000
    Brazil

    Site Not Available

  • Novartis Investigative Site

    Beijing 1816670, Beijing Municipality 2038349 100034
    China

    Site Not Available

  • Novartis Investigative Site

    Chongqing, Chongqing 400010
    China

    Site Not Available

  • Novartis Investigative Site

    Chongqing 1814906, Chongqing Municipality 1814905 400010
    China

    Site Not Available

  • Novartis Investigative Site

    Guangzhou, Guangdong 510623
    China

    Site Not Available

  • Novartis Investigative Site

    Shenzhen, Guangdong 518034
    China

    Site Not Available

  • Novartis Investigative Site

    Guangzhou 1809858, Guangdong 1809935 510623
    China

    Site Not Available

  • Novartis Investigative Site

    Shenzhen 1795565, Guangdong 1809935 518034
    China

    Site Not Available

  • Novartis Investigative Site

    Chengdu, Sichuan 610041
    China

    Site Not Available

  • Novartis Investigative Site

    Chengdu 1815286, Sichuan 1794299 610041
    China

    Site Not Available

  • Novartis Investigative Site

    Hangzhou, Zhejiang 310052
    China

    Site Not Available

  • Novartis Investigative Site

    Hangzhou 1808926, Zhejiang 1784764 310052
    China

    Site Not Available

  • Novartis Investigative Site

    Beijing, 100069
    China

    Site Not Available

  • Peking University First Hospital

    Beijing, 100034
    China

    Site Not Available

  • Peking University First Hospital

    Beijing 1816670, 100034
    China

    Site Not Available

  • Novartis Investigative Site

    Bogota, 110231
    Colombia

    Site Not Available

  • Paediatric Neurology

    Copenhagen, 2100 O
    Denmark

    Site Not Available

  • Novartis Investigative Site

    Copenhagen 2618425, 2100 O
    Denmark

    Site Not Available

  • Paediatric Neurology

    Copenhagen 2618425, 2100 O
    Denmark

    Site Not Available

  • Novartis Investigative Site

    Cairo, Abbassia 3753450
    Egypt

    Site Not Available

  • Novartis Investigative Site

    Thessaloniki, 54642
    Greece

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  • Sir Ganga Ram Hospital

    New Delhi, Delhi 110 060
    India

    Site Not Available

  • Novartis Investigative Site

    New Delhi 1261481, National Capital Territory of Delhi 1273293 110060
    India

    Site Not Available

  • Sir Ganga Ram Hospital

    New Delhi 1261481, National Capital Territory of Delhi 1273293 110 060
    India

    Site Not Available

  • Novartis Investigative Site

    Kolkata, West Bengal 700094
    India

    Site Not Available

  • Novartis Investigative Site

    Kolkata 1275004, West Bengal 1252881 700094
    India

    Site Not Available

  • Novartis Investigative Site

    Hyderabad, 500034
    India

    Site Not Available

  • Novartis Investigative Site

    Hyderabad 1269843, 500034
    India

    Site Not Available

  • Novartis Investigative Site

    Kozhikode, 673016
    India

    Site Not Available

  • P.D. Hinduja National Hospital & MRC

    Mumbai, 400016
    India

    Site Not Available

  • Novartis Investigative Site

    Mumbai 1275339, 400016
    India

    Site Not Available

  • P.D. Hinduja National Hospital & MRC

    Mumbai 1275339, 400016
    India

    Site Not Available

  • AIIMS, Ansari Nagar

    New Delhi, 110029
    India

    Site Not Available

  • AIIMS, Ansari Nagar

    New Delhi 1261481, 110029
    India

    Site Not Available

  • Novartis Investigative Site

    Kuala Lumpur, 50300
    Malaysia

    Site Not Available

  • Novartis Investigative Site

    Kuala Lumpur 1735161, 59100
    Malaysia

    Site Not Available

  • Novartis Investigative Site

    Mexico, Distrito Federal 06720
    Mexico

    Site Not Available

  • Hospital Civil De Guadalajara Fray Antonio Alcalde

    Guadalajara, Jalisco 44280
    Mexico

    Site Not Available

  • Hospital Civil De Guadalajara Fray Antonio Alcalde

    Guadalajara 4005539, Jalisco 4004156 44280
    Mexico

    Site Not Available

  • Novartis Investigative Site

    Guadalajara 4005539, Jalisco 4004156 44280
    Mexico

    Site Not Available

  • Novartis Investigative Site

    Mexico City 3530597, Mexico City 3527646 06720
    Mexico

    Site Not Available

  • Novartis Investigative Site

    Riyadh, 11211
    Saudi Arabia

    Site Not Available

  • Novartis Investigative Site

    Riyadh 108410, 11211
    Saudi Arabia

    Site Not Available

  • Novartis Investigative Site

    Singapore, 119074
    Singapore

    Site Not Available

  • Novartis Investigative Site

    Singapore 1880252, 119074
    Singapore

    Site Not Available

  • Red Cross War Memorial Childrens Hospital

    Cape Town, 7925
    South Africa

    Site Not Available

  • Novartis Investigative Site

    Cape Town 3369157, 7925
    South Africa

    Site Not Available

  • Red Cross War Memorial Childrens Hospital

    Cape Town 3369157, 7925
    South Africa

    Site Not Available

  • Kaohsiung Medical University Hospital

    Kaohsiung, 80756
    Taiwan

    Site Not Available

  • Kaohsiung Medical University Hospital

    Kaohsiung City 1673820, 80756
    Taiwan

    Site Not Available

  • Novartis Investigative Site

    Kaohsiung City 1673820, 80756
    Taiwan

    Site Not Available

  • Siriraj Hospital

    Bangkok, 10700
    Thailand

    Site Not Available

  • Novartis Investigative Site

    Bangkok 1609350, 10700
    Thailand

    Site Not Available

  • Siriraj Hospital

    Bangkok 1609350, 10700
    Thailand

    Site Not Available

  • Novartis Investigative Site

    Little Rock, Arkansas 72202
    United States

    Site Not Available

  • Novartis Investigative Site

    Oakland, California 94609
    United States

    Site Not Available

  • Connecticut Children's Medical Center

    Farmington, Connecticut 06032
    United States

    Site Not Available

  • Connecticut Children's Medical Center

    Farmington 4834272, Connecticut 4831725 06032
    United States

    Site Not Available

  • Ann & Robert H. Lurie Children's Hospital of Chicago

    Chicago, Illinois 60611
    United States

    Site Not Available

  • Ann & Robert H. Lurie Children's Hospital of Chicago

    Chicago 4887398, Illinois 4896861 60611
    United States

    Site Not Available

  • Clinic for Special Children

    Strasburg, Pennsylvania 17579
    United States

    Site Not Available

  • Clinic for Special Children

    Strasburg 4561542, Pennsylvania 6254927 17579
    United States

    Site Not Available

  • St Jude Children's Research Hospital

    Memphis, Tennessee 38105
    United States

    Site Not Available

  • St Jude Children's Research Hospital

    Memphis 4641239, Tennessee 4662168 38105
    United States

    Site Not Available

  • Children's Specialty Group/CHKD

    Norfolk, Virginia 23507
    United States

    Site Not Available

  • Child Hosp Of The Kings Daughters

    Norfolk 4776222, Virginia 6254928 23507
    United States

    Site Not Available

  • Children's Specialty Group/CHKD

    Norfolk 4776222, Virginia 6254928 23507
    United States

    Site Not Available

  • National Children's Hospital

    Hanoi, 100000
    Vietnam

    Site Not Available

  • National Children's Hospital

    Hanoi 1581130, 100000
    Vietnam

    Site Not Available

  • Novartis Investigative Site

    Hanoi 1581130, 100000
    Vietnam

    Site Not Available

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