Phase IIIb, Open-label, Multi-center Study to Evaluate Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally to Participants With SMA Who Discontinued Treatment With Nusinersen or Risdiplam

Phase 3

Completed

• Conditions: Spinal Muscular Atrophy
• Interventions: Genetic: OAV101

• Registration Number: NCT05386680
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This is an open-label, single arm, multi-center study. Approximately 28 participants aged 2 to \<18 years will be enrolled stratified as 2 to 5 years and 6 to \< 18 years. The study is comprised of 3 periods, Screening (up to 45 days), Treatment (1 day), and Follow-up (52 weeks).

Detailed Description

During the Screening period and on Day -1 (Baseline), eligibility will be assessed, including confirmation that nusinersen (Spinraza®) or risdiplam (Evrysdi®) have not been used for the defined period (4 month and 15 days prior to Day -1 respectively). On Day - 1 (Baseline) participants will be admitted to the hospital for pre-treatment baseline procedures. Prednisolone (or equivalent) will be given and continued as per the study protocol.

Participants who meet eligibility criteria at Screening and Baseline will receive a single dose of OAV101 (1.2 x 10\^14 vector genomes) by lumbar intrathecal injection on Day 1 (Treatment) and will then undergo in-patient safety monitoring atleast the next 48 hours, after which the participant may be discharged according to Investigator judgement.

During Follow-up, safety monitoring will continue as per the visits defined in the Assessment Schedule. Safety for participants enrolled will be evaluated by the study team together with the Data Monitoring Committee (DMC).

Final analysis will be performed after all participants have completed Week 52 or discontinued prior to Week 52. At the end of study, participants will be invited to enroll in a Novartis-sponsored long-term follow-up study to monitor long-term safety and efficacy.

Study Timeline

• Study First Submitted: 2022-05-18
• Study First Submitted QC: 2022-05-18
• Study First Posted: 2022-05-23
• Study Start: 2023-01-12
• Primary Completion: 2024-11-29
• Study Completion: 2024-11-29
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-09
• Last Update Posted: 2025-01-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

Not provided

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Exclusion Criteria

• Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer using an immunoassay is reported as elevated

• Clinically significant abnormalities in test results during screening

• Contraindications for lumbar puncture procedure

• At Baseline, participants are excluded if they received:

  • nusinersen (Spinraza®) or
  • risdiplam (Evrysdi®) within a defined timeframe

• Vaccinations 2 weeks prior to administration of OAV101

• Hospitalization for a pulmonary event, or for nutritional support within 2 months prior to Screening or inpatient major surgery planned.

• Presence of an infection or febrile illness up to 30 days prior to administration of OAV101

• Requiring invasive ventilation

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
OAV-101	OAV101	Intrathecal administration of OAV101 at a dose of 1.2 x 10\^14 vector genomes, one time dose

Primary Outcome Measures

Name	Time	Method
Number and percentage of participants reporting AEs, related AEs, SAEs, and AESIs	52 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. 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.; An AESI is primarily defined by using standard Medical Dictionary for Regulatory Activities (MedDRA) queries, and identified as follows: Hepatotoxicity, Thrombocytopenia, Thrombotic microangiopathy, Cardiac adverse events, and Dorsal root ganglia toxicity

Secondary Outcome Measures

Name	Time	Method
Change from baseline to Week 52 visit in the RULM total Score	52 weeks	The Revised Upper Limb Model (RULM) is a validated, SMA-specific assessment that measures motor performance in the upper limbs from childhood through adulthood in ambulatory and never ambulatory individuals with SMA. The revised version of the test 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). These item scores are summed to give a total score ranging from 0 to 37 points with lower scores reflecting poorer ability.
Change from baseline to Week 52 visit in Assessment of Caregiver Experience in ACEND instrument score	52 weeks	The Assessment of Caregiver Experience in Neuromuscular Disease (ACEND) instrument quantifies the caregiver impact experienced by parents/caregivers of children affected with severe neuromuscular diseases, including children with SMA The total score is on a scale of 0 to 100 with a higher score indicating a greater impact on the caregiver.
Change from baseline to Week 52 visit in the HFMSE total score	52 weeks	The Hammersmith Functional Motor Scale Expanded (HFMSE) is a SMA-specific 33-item assessment that is administered by clinical evaluators in a short period of time, requires minimal equipment, and is designed to factor in patient fatigue. Each motor skill item is scored on a 3-point Likert scale from 0 (no response) to 2 (full response), with a total score range of 0 to 66. A higher score indicates a higher ability level.

Trial Locations

Locations (4)

Boston Childrens Hospital; 🇺🇸 Boston, Massachusetts, United States

Child Hosp Of The Kings Daughters; 🇺🇸 Norfolk, Virginia, United States

University of Wisconsin Madison Medical School; 🇺🇸 Madison, Wisconsin, United States

Novartis Investigative Site; 🇪🇸 Barcelona, Catalunya, Spain