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

A Randomized, Sham-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Intrathecal OAV101 in Type 2 Spinal Muscular Atrophy (SMA) Patients Who Are ≥ 2 to < 18 Years of Age, Treatment Naive, Sitting, and Never Ambulatory

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Spinal Muscular Atrophy
• Intervention / Treatment: Genetic: OAV101; Procedure: Sham control

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.

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Paraná
    • Curitiba, Paraná, Brazil, 81520-060
      • Novartis Investigative Site
  • São Paulo
    • São Paulo, São Paulo, Brazil, 05403 000
      • Novartis Investigative Site
• China
  • Beijing, China, 100730
    • Novartis Investigative Site
  • Beijing, China, 100034
    • Peking University First Hospital
  • Beijing, China, 100069
    • Novartis Investigative Site
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100034
      • Novartis Investigative Site
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400010
      • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510623
      • Novartis Investigative Site
    • Shenzhen, Guangdong, China, 518034
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310052
      • Novartis Investigative Site
• Denmark
  • Copenhagen, Denmark, 2100 O
    • Novartis Investigative Site
  • Copenhagen, Denmark, 2100 O
    • Paediatric Neurology
• India
  • Hyderabad, India, 500034
    • Novartis Investigative Site
  • Mumbai, India, 400016
    • Novartis Investigative Site
  • Mumbai, India, 400016
    • P.D. Hinduja National Hospital & MRC
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110029
      • Novartis Investigative Site
    • New Delhi, National Capital Territory of Delhi, India, 110060
      • Novartis Investigative Site
    • New Delhi, National Capital Territory of Delhi, India, 110 060
      • Sir Ganga Ram Hospital
  • New Delhi
    • New Delhi, New Delhi, India, 110029
      • AIIMS, Ansari Nagar
  • West Bengal
    • Kolkata, West Bengal, India, 700094
      • Novartis Investigative Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Novartis Investigative Site
  • Kuala Lumpur, Malaysia, 50300
    • Novartis Investigative Site
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Hospital Civil de Guadalajara Fray Antonio Alcalde
    • Guadalajara, Jalisco, Mexico, 44280
      • Novartis Investigative Site
  • Mexico City
    • Mexico City, Mexico City, Mexico, 06720
      • Novartis Investigative Site
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11211
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
• South Africa
  • Cape Town, South Africa, 7925
    • Novartis Investigative Site
  • Cape Town, South Africa, 7925
    • Red Cross War Memorial Childrens Hospital
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Novartis Investigative Site
  • Kaohsiung City, Taiwan, 80756
    • Kaohsiung Medical University Hospital
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
• United States
  • Connecticut
    • Farmington, Connecticut, United States, 06032
      • Connecticut Children's Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Pennsylvania
    • Strasburg, Pennsylvania, United States, 17579
      • Clinic for Special Children
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St Jude Children's Research Hospital
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Specialty Group/CHKD
    • Norfolk, Virginia, United States, 23507
      • Child Hosp Of The Kings Daughters
• Vietnam
  • Hanoi, Vietnam, 100000
    • Novartis Investigative Site
  • Hanoi, Vietnam, 100000
    • National Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Key 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.

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) 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Genetic: OAV101; Gene therapy; Other Names: Zolgensma; AVXS-101
Sham Comparator: 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)	Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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)
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	The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. The scale consists of 19 scorable items: 18 items scored on 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). Total scores range from 0-37 points. Higher scores reflect higher level of motor ability.	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	The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. The scale consists of 19 scorable items: 18 items scored on a 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). Total scores range from 0-37 points. Higher scores reflect higher level of motor ability.	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	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) (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	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)(end of Period 1)
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. A Treatment Emergent Adverse Event (TEAE) is defined as an event that emerges during treatment, having been absent pretreatment, or worsens relative to the pretreatment state. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments. pt = participant pts = participants	Adverse events are reported from the start of treatment period 1 plus 64 weeks, up to a maximum time period of 64 weeks.
Number of Participants With Adverse Events of Special Interest (AESI)	An AESI is primarily defined by using standard Medical Dictionary for Regulatory Activities (MedDRA) queries, and identified as follows: Hepatotoxicity; Thrombocytopenia; Cardiac adverse events; Signs and symptoms that may be suggestive of dorsal root ganglia toxicity; Thrombotic microangiopathy; New malignancies Adverse events for Periods 1 and 2 are combined in the overall OAV101 arm because the same active treatment (and same single dose) was administered in either Period1 or Period 2. Because this is a gene therapy, which permanently impacts the genetics of the study participant, participants randomized to OAV101 in Period 1 are still considered on treatment with OAV101 in Period 2 (after receiving sham control in Period 2). Therefore, adverse events for the Sham arm can only be considered from Period 1.	Adverse events are reported from the start of treatment period 1 plus 64 weeks, up to a maximum time period of 64 weeks.
Number (and Percentage) of Patients With Intracardiac Thrombi	Intracardiac thrombi is defined as the presence of thrombus on post-baseline echocardiograms. Events for Periods 1 and 2 are combined in the overall OAV101 arm because the same active treatment (and same single dose) was administered in either Period1 or Period 2. Because this is a gene therapy, which permanently impacts the genetics of the study participant, participants randomized to OAV101 in Period 1 are still considered on treatment with OAV101 in Period 2 (after receiving sham control in Period 2). Therefore, events for the Sham arm can only be considered from Period 1.	Baseline up to 64 weeks
Number(and Percentage) of Patients With Low Cardiac Function	Low cardiac function is defined as left ventricular ejection fraction <56% or left ventricular fractional shortening <28% on post-baseline echocardigrams. Events for Periods 1 and 2 are combined in the overall OAV101 arm because the same active treatment (and same single dose) was administered in either Period1 or Period 2. Because this is a gene therapy, which permanently impacts the genetics of the study participant, participants randomized to OAV101 in Period 1 are still considered on treatment with OAV101 in Period 2 (after receiving sham control in Period 2). Therefore, events for the Sham arm can only be considered from Period 1.	Baseline up to 64 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Helpful Links

• Results for COAV101B12301 from the Novartis Clinical Trials Website
• A Plain Language Trial Summary is available on www.novctrd.com
• A Pediatric Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): November 12, 2024
• Study Completion (Actual): April 29, 2025

Study Registration Dates

• First Submitted: October 11, 2021
• First Submitted That Met QC Criteria: October 11, 2021
• First Posted (Actual): October 22, 2021

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: pediatric; gene therapy; spinal muscular atrophy; SMA; Muscle atrophy; muscle wasting; muscle function; myopathy; Zolgensma; OAV101; AVXS 101; atrophied muscle; loss of muscle strength
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Neuromuscular Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Atrophy; Motor Neuron Disease; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Muscular Diseases; Muscular Atrophy; Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood; Zolgensma
• Other Study ID Numbers: COAV101B12301; 2021-003474-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No