Skip to main content
OpenTrials
Completed

NCT Number: NCT05089656

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Type 2 Spinal Muscular Atrophy Atrophy Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Motor Neuron Disease Muscular Atrophy Muscular Atrophy, Spinal Muscular Diseases Musculoskeletal Diseases Nervous System Diseases Neurodegenerative Diseases Neurologic Manifestations Neuromuscular Diseases Neuromuscular Manifestations Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Signs and Symptoms Spinal Cord Diseases Spinal Muscular Atrophies of Childhood

Age range

2 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Novartis Investigative Site, Curitiba, Paraná, Brazil

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

OAV101

Genetic

Gene therapy

Other names: Zolgensma, AVXS-101

Sham Control

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.

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

    Time frame: Baseline, Week 52 (or Week 48)

    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.

Secondary outcomes

  1. 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

    Time frame: Baseline, Week 52 (or Week 48)

    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.

  2. 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

    Time frame: Baseline, Week 52 (or Week 48)

    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.

  3. 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

    Time frame: Baseline, Week 52 (or Week 48)

    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.

  4. % 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

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

    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.

  5. % 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

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

    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.

  6. Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events

    Time frame: Adverse events are reported from the start of treatment period 1 plus 64 weeks, up to a maximum time period of 64 weeks.

    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

  7. Number of Participants With Adverse Events of Special Interest (AESI)

    Time frame: Adverse events are reported from the start of treatment period 1 plus 64 weeks, up to a maximum time period of 64 weeks.

    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.

  8. Number (and Percentage) of Patients With Intracardiac Thrombi

    Time frame: Baseline up to 64 weeks

    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.

  9. Number(and Percentage) of Patients With Low Cardiac Function

    Time frame: Baseline up to 64 weeks

    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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

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

Acronym: STEER

Important dates

Study start
2022
Primary completion
2024
Study completion
2025
First posted
Oct 22, 2021
Registry last updated
Jan 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.