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 (STRENGTH)

• ClinicalTrials.gov Identifier: NCT05386680
• Recruitment Status: Active, not recruiting
• First Posted: May 23, 2022
• Last Update Posted: January 19, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: May 18, 2022
• First Posted Date: May 23, 2022
• Last Update Posted Date: January 19, 2024
• Actual Study Start Date: January 12, 2023
• Estimated Primary Completion Date: December 3, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 18, 2022)

Number and percentage of participants reporting AEs, related AEs, SAEs, and AESIs [ Time Frame: 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 18, 2022)

• Change from baseline to Week 52 visit in the HFMSE total score [ Time Frame: 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.
• Change from baseline to Week 52 visit in the RULM total Score [ Time Frame: 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 [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: Phase IIIb, Open-label, Single-arm, Multi-center Study to Evaluate the Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally (1.2 x 10^14 Vector Genomes) to Participants 2 to < 18 Years of Age With Spinal Muscular Atrophy (SMA) Who Have Discontinued Treatment With Nusinersen (Spinraza®) or Risdiplam (Evrysdi®)
• 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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Spinal Muscular Atrophy

Intervention

Genetic: OAV101

Intrathecal administration of OAV101 at a dose of 1.2 x 10^14 vector genomes, one time dose

Other Names:

• AVXS-101
• Zolgensma

Study Arms

Experimental: OAV-101

Intrathecal administration of OAV101 at a dose of 1.2 x 10^14 vector genomes, one time dose

Intervention: Genetic: OAV101

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 16, 2024): 27
• Original Estimated Enrollment (submitted: May 18, 2022): 28
• Estimated Study Completion Date: December 3, 2024
• Estimated Primary Completion Date: December 3, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

• SMA diagnosis
• Aged 2 to < 18 years
• Have had at least four loading doses of nusinersen (Spinraza®) or at least 3 months of treatment with risdiplam (Evrysdi®) at Screening
• Must have symptoms of SMA as defined in the protocol

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, France, Italy, Japan, Netherlands, Spain, United States

Administrative Information

• NCT Number: NCT05386680
• Other Study ID Numbers: COAV101B12302
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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/.
• URL: https://www.clinicalstudydatarequest.com/

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: January 2024