NCT05089656

Brief 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.

Trial Health

98
On Track

Trial Health Score

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

Enrollment
126

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Feb 2022

Typical duration for phase_3

Geographic Reach
13 countries

42 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

October 11, 2021

Completed
11 days until next milestone

First Posted

Study publicly available on registry

October 22, 2021

Completed
3 months until next milestone

Study Start

First participant enrolled

February 1, 2022

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 12, 2024

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 29, 2025

Completed
7 months until next milestone

Results Posted

Study results publicly available

December 8, 2025

Completed
Last Updated

January 13, 2026

Status Verified

December 1, 2025

Enrollment Period

2.8 years

First QC Date

October 11, 2021

Results QC Date

October 27, 2025

Last Update Submit

December 18, 2025

Conditions

Keywords

ZolgensmaOAV101AVXS 101gene therapyMuscle atrophySMAspinal muscular atrophymuscle functionmyopathymuscle wastingatrophied muscleloss of muscle strengthpediatric

Outcome Measures

Primary Outcomes (1)

  • Change From Baseline at the End of Period 1 in the Hammersmith Functional Motor Scale Expanded - Total Score - in the ≥ 2 to < 18 Years Age Group

    The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.

    Baseline, Week 52 (or Week 48)

Secondary Outcomes (9)

  • Change From Baseline in HFMSE Total Score at the End of Follow-up Period 1 in Treated Patients Compared to Sham Controls in the ≥ 2 to < 5 Years Age Group

    Baseline, Week 52 (or Week 48)

  • Change From Baseline in Revised Upper Limb Module (RULM) Total Score at the End of Follow-up Period 1 in Treated Patients Compared to Sham Controls in the ≥ 2 to < 18 Years Age Group

    Baseline, Week 52 (or Week 48)

  • Change From Baseline in the RULM Total Score at the End of Follow-up Period 1 in Treated Patients Compared to Sham Controls in the ≥ 2 to < 5 Years Age Group

    Baseline, Week 52 (or Week 48)

  • % of Participants Who Achieved at Least a 3-point Improvement From Baseline in HFMSE Total Score at the End of Follow-up Period 1 in the ≥ 2 to < 18 Years Age Group

    Baseline, Week 52 (or Week 48) (end of Period 1)

  • % of Participants Who Achieved at Least a 3-point Improvement From Baseline in HFMSE Total Score at the End of Follow-up Period 1 for Participants Aged ≥ 2 to < 5 Years

    Baseline, Week 52 (or Week 48)(end of Period 1)

  • +4 more secondary outcomes

Study Arms (2)

OAV101 in Treatment Period 1; Sham Control in Treatment Period 2

EXPERIMENTAL

OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Treatment Period 1; Sham Control in Treatment Period 2 (Week 52 +1 day).

Genetic: OAV101

Sham control in Treatment Period 1; OAV101 in Treatment Period 2

SHAM COMPARATOR

A skin prick in the lumbar region in Treat Period 1; OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg) in Treatment Period 2 (Week 52 +1 day)

Procedure: Sham control

Interventions

OAV101GENETIC

Gene therapy

Also known as: Zolgensma, AVXS-101
OAV101 in Treatment Period 1; Sham Control in Treatment Period 2
Sham controlPROCEDURE

The sham procedure will consist of a small needle prick on the lower back at the location where the LP injection is normally made. The needle will break the skin, but no needle insertion for lumbar puncture will occur.

Sham control in Treatment Period 1; OAV101 in Treatment Period 2

Eligibility Criteria

Age2 Years - 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Diagnostic confirmation during screening period of 5q SMA
  • The patient must be treatment naive (historical or current use) for all SMN-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 during the screening period for trial eligibility
  • Able to sit independently at screening, but has never had the ability to walk independently.

You may not qualify if:

  • Anti-adeno-associated virus serotype 9 (AAV9) antibody titer reported as elevated (reference to \> 1:50 or validated result consistent with being elevated) at screening as determined by sponsor designated lab.
  • Infectious process (e.g., viral, bacterial) or febrile illness within 30 days prior to OAV101 treatment or sham procedure
  • Hepatic dysfunction (i.e. alanine aminotransferase (ALT), total bilirubin, gamma-glutamyl transferase (GGT) or glutamate dehydrogenase (GLDH), \> upper limit of normal (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 or requiring tracheostomy
  • Complications at screening that would interfere with motor efficacy assessments including but not limited to, severe contractures or Cobb angle \> 40 in a sitting position
  • Surgery for scoliosis or hip fixation in the 12 months prior to Screening or planned within the next 64 weeks
  • Clinically significant sensory abnormalities in the neurological examination at Screening

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (42)

Connecticut Children's Medical Center

Farmington, Connecticut, 06032, United States

Location

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

Chicago, Illinois, 60611, United States

Location

Clinic for Special Children

Strasburg, Pennsylvania, 17579, United States

Location

St Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Child Hosp Of The Kings Daughters

Norfolk, Virginia, 23507, United States

Location

Children's Specialty Group/CHKD

Norfolk, Virginia, 23507, United States

Location

Novartis Investigative Site

Curitiba, Paraná, 81520-060, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403 000, Brazil

Location

Novartis Investigative Site

Beijing, Beijing Municipality, 100034, China

Location

Novartis Investigative Site

Chongqing, Chongqing Municipality, 400010, China

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510623, China

Location

Novartis Investigative Site

Shenzhen, Guangdong, 518034, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310052, China

Location

Peking University First Hospital

Beijing, 100034, China

Location

Novartis Investigative Site

Beijing, 100069, China

Location

Novartis Investigative Site

Beijing, 100730, China

Location

Novartis Investigative Site

Copenhagen, 2100 O, Denmark

Location

Paediatric Neurology

Copenhagen, 2100 O, Denmark

Location

Sir Ganga Ram Hospital

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

Location

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Novartis Investigative Site

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

Location

AIIMS, Ansari Nagar

New Delhi, New Delhi, 110029, India

Location

Novartis Investigative Site

Kolkata, West Bengal, 700094, India

Location

Novartis Investigative Site

Hyderabad, 500034, India

Location

Novartis Investigative Site

Mumbai, 400016, India

Location

P.D. Hinduja National Hospital & MRC

Mumbai, 400016, India

Location

Novartis Investigative Site

Kuala Lumpur, 50300, Malaysia

Location

Novartis Investigative Site

Kuala Lumpur, 59100, Malaysia

Location

Hospital Civil De Guadalajara Fray Antonio Alcalde

Guadalajara, Jalisco, 44280, Mexico

Location

Novartis Investigative Site

Guadalajara, Jalisco, 44280, Mexico

Location

Novartis Investigative Site

Mexico City, Mexico City, 06720, Mexico

Location

Novartis Investigative Site

Riyadh, 11211, Saudi Arabia

Location

Novartis Investigative Site

Singapore, 119074, Singapore

Location

Novartis Investigative Site

Cape Town, 7925, South Africa

Location

Red Cross War Memorial Childrens Hospital

Cape Town, 7925, South Africa

Location

Kaohsiung Medical University Hospital

Kaohsiung City, 80756, Taiwan

Location

Novartis Investigative Site

Kaohsiung City, 80756, Taiwan

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

National Children's Hospital

Hanoi, 100000, Vietnam

Location

Novartis Investigative Site

Hanoi, 100000, Vietnam

Location

Related Publications (1)

  • Proud CM, Vu DC, Wilmshurst JM, Sanmaneechai O, Gulati S, Xiong H, Moreno HC, Tay SKH, Thong MK, Born AP, Banzzatto Ortega A, Jong YJ, Al-Muhaizea MA, Lee AW, Visootsak J, Tauscher-Wisniewski S, Alecu I, Parlikar R, Finkel RS; STEER Study Group. Intrathecal onasemnogene abeparvovec in treatment-naive patients with spinal muscular atrophy: a phase 3, randomized controlled trial. Nat Med. 2026 Feb;32(2):481-487. doi: 10.1038/s41591-025-04103-w. Epub 2025 Dec 8.

Related Links

MeSH Terms

Conditions

Spinal Muscular Atrophies of ChildhoodMuscular AtrophyMuscular Atrophy, SpinalMuscular Diseases

Interventions

Zolgensma

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesMotor Neuron DiseaseNeuromuscular DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesNeuromuscular ManifestationsNeurologic ManifestationsAtrophyPathological Conditions, AnatomicalPathological Conditions, Signs and SymptomsSigns and SymptomsMusculoskeletal Diseases

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Model Details: A participant will receive a single, one-time dose of OAV101.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 11, 2021

First Posted

October 22, 2021

Study Start

February 1, 2022

Primary Completion

November 12, 2024

Study Completion

April 29, 2025

Last Updated

January 13, 2026

Results First Posted

December 8, 2025

Record last verified: 2025-12

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