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: Completed; Phase 3

Conditions: Spinal Muscular Atrophy

Treatments: Genetic: OAV101

Study type: Interventional

Funder types: Industry

Identifiers

NCT05386680

COAV101B12302

Details and patient eligibility

About

This was a Phase IIIb open-label, single arm, multi-center study to evaluate the safety, tolerability and efficacy of OAV101B in participants with SMA aged 2 to <18 years after the discontinuation of treatment with nusinersen or risdiplam. The study aimed to enroll approximately 28 participants across each of 2 age brackets (2 to <6 years, and 6 to <18 years).

Full description

Eligible participants received a single OAV101B administration of 1.2x1014 vector genomes on Day 1 (Treatment period) and were followed for a period of 52 weeks.

Participants were admitted to the hospital on Day -1 for pre-treatment baseline procedures. After receiving OAV101B on Day 1, participants underwent in-patient safety monitoring over the next 48 hours, after which the participant could be discharged, based on Investigator judgment.

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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27 participants in 1 patient group

OAV-101

Experimental group

Description:

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

Treatment:

Genetic: OAV101