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)

Novartis

Status and phase

Active, not recruiting

Phase 3

Conditions

Spinal Muscular Atrophy

Treatments

Genetic: OAV101

Study type

Interventional

Funder types

Industry

Identifiers

NCT05386680

COAV101B12302

Details and patient eligibility

About

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).

Full 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.

Enrollment

27 patients

Sex

All

Ages

2 to 17 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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