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

NCT ID: NCT05089656

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-01
• Study Completion Date: 2025-04-29

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.

Detailed 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.

Conditions

Type 2 Spinal Muscular Atrophy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

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).

Group Type: EXPERIMENTAL

OAV101

Intervention Type: GENETIC

Gene therapy

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

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)

Group Type: SHAM_COMPARATOR

Sham control

Intervention Type: PROCEDURE

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.

Interventions

Sham control

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.

Intervention Type: PROCEDURE

OAV101

Gene therapy

Intervention Type: GENETIC

Other Intervention Names

Zolgensma; AVXS-101

Eligibility Criteria

Inclusion Criteria

• 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.

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) 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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Connecticut Children's Medical Center

Farmington, Connecticut, United States

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

Chicago, Illinois, United States

Clinic for Special Children

Strasburg, Pennsylvania, United States

St Jude Children's Research Hospital

Memphis, Tennessee, United States

Child Hosp Of The Kings Daughters

Norfolk, Virginia, United States

Children's Specialty Group/CHKD

Norfolk, Virginia, United States

Novartis Investigative Site

Curitiba, Paraná, Brazil

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Novartis Investigative Site

Beijing, Beijing Municipality, China

Novartis Investigative Site

Chongqing, Chongqing Municipality, China

Novartis Investigative Site

Guangzhou, Guangdong, China

Novartis Investigative Site

Shenzhen, Guangdong, China

Novartis Investigative Site

Chengdu, Sichuan, China

Novartis Investigative Site

Hangzhou, Zhejiang, China

Peking University First Hospital

Beijing, , China

Novartis Investigative Site

Beijing, , China

Novartis Investigative Site

Beijing, , China

Novartis Investigative Site

Copenhagen, , Denmark

Paediatric Neurology

Copenhagen, , Denmark

Sir Ganga Ram Hospital

New Delhi, National Capital Territory of Delhi, India

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, India

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, India

AIIMS, Ansari Nagar

New Delhi, New Delhi, India

Novartis Investigative Site

Kolkata, West Bengal, India

Novartis Investigative Site

Hyderabad, , India

Novartis Investigative Site

Mumbai, , India

P.D. Hinduja National Hospital & MRC

Mumbai, , India

Novartis Investigative Site

Kuala Lumpur, , Malaysia

Novartis Investigative Site

Kuala Lumpur, , Malaysia

Hospital Civil De Guadalajara Fray Antonio Alcalde

Guadalajara, Jalisco, Mexico

Novartis Investigative Site

Guadalajara, Jalisco, Mexico

Novartis Investigative Site

Mexico City, Mexico City, Mexico

Novartis Investigative Site

Riyadh, , Saudi Arabia

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Cape Town, , South Africa

Red Cross War Memorial Childrens Hospital

Cape Town, , South Africa

Kaohsiung Medical University Hospital

Kaohsiung City, , Taiwan

Novartis Investigative Site

Kaohsiung City, , Taiwan

Novartis Investigative Site

Bangkok, , Thailand

Siriraj Hospital

Bangkok, , Thailand

National Children's Hospital

Hanoi, , Vietnam

Novartis Investigative Site

Hanoi, , Vietnam

Countries

United States; Brazil; China; Denmark; India; Malaysia; Mexico; Saudi Arabia; Singapore; South Africa; Taiwan; Thailand; Vietnam

References

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. 2025 Dec 8. doi: 10.1038/s41591-025-04103-w. Online ahead of print.

Reference Type: DERIVED

PMID: 41360993 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=18373

Results for COAV101B12301 from the Novartis Clinical Trials Website

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2997

A Plain Language Trial Summary is available on www.novctrd.com

https://www.novctrd.com/ctrdweb/ppatientsummary/ppatientsummaries?periodicPatientSummaryId=806

A Pediatric Plain Language Trial Summary is available on www.novctrd.com

Other Identifiers

2021-003474-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

COAV101B12301

Identifier Type: -

Identifier Source: org_study_id