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

Spinal Muscular Atrophy Clinical Trial

— STRENGTH  

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®)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05386680
• Other study ID #: COAV101B12302
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 12, 2023
• Est. completion date: December 3, 2024

Study information

• Verified date: January 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 27
• Est. completion date: December 3, 2024
• Est. primary completion date: December 3, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy

Intervention

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

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Parkville	Victoria
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Montreal	Quebec
France	Novartis Investigative Site	Bron Cedex
France	Novartis Investigative Site	Toulouse Cedex
Italy	Novartis Investigative Site	Roma	RM
Japan	Novartis Investigative Site	Kurume city	Fukuoka
Japan	Novartis Investigative Site	Shinjuku ku	Tokyo
Netherlands	Novartis Investigative Site	Utrecht
Spain	Novartis Investigative Site	Barcelona	Catalunya
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Madison	Wisconsin
United States	Novartis Investigative Site	Norfolk	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Italy,  Japan,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and percentage of participants reporting AEs, related AEs, SAEs, and AESIs	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	52 weeks
Secondary	Change from baseline to Week 52 visit in the HFMSE total score	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.	52 weeks
Secondary	Change from baseline to Week 52 visit in the RULM total Score	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.	52 weeks
Secondary	Change from baseline to Week 52 visit in Assessment of Caregiver Experience in ACEND instrument score	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.	52 weeks