A Study Evaluating the Effectiveness and Safety of Risdiplam Administered as an Early Intervention in Pediatric Participants With Spinal Muscular Atrophy After Gene Therapy
Study Details
Study Description
Brief Summary
This is an open-label, single-arm, multicenter clinical study to evaluate the effectiveness and safety of risdiplam administered as an early intervention in pediatric participants with spinal muscular atrophy (SMA) and 2 SMN2 copies who have previously received onasemnogene abeparvovec. Participants are children < 2 years of age genetically diagnosed with SMA.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Risdiplam Participants will receive risdiplam orally once daily for 72 weeks (Treatment Period). The Treatment Period will be followed by a 1-year Treatment Extension Period for a total study duration of 120 weeks (approximately 2.5 years) for each participant enrolled. |
Drug: risdiplam
Participants will receive risdiplam orally at the currently approved dose. The dose should be adapted for weight and age.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Change from Baseline in the Raw Score of Bayley Scales of Infant and Toddler Development - Third Edition (BSID-III) Gross Motor Score at 72 Weeks of Risdiplam Treatment [Baseline, Week 72]
Secondary Outcome Measures
- Change from Baseline in Bulbar/Swallowing Function Assessment as Measured by the Oral and Swallowing Abilities Tool (OrSAT) at 72 Weeks of Risdiplam Treatment [Baseline, Week 72]
- Percentage of Participants With a Gross Motor Quotient (GMQ) Between 80-110 as Measured by the Peabody Developmental Motor Scale, Second Edition (PDMS-2) at 72 Weeks of Risdiplam Treatment [Baseline, Week 72]
- Percentage of Participants With a Fine Motor Quotient (FMQ) Between 80-110 as Measured by the PDMS-2 at 72 Weeks of Risdiplam Treatment [Baseline, Week 72]
- Percentage of Participants With Improvement or No Change in Respiratory Illness as Assessed by Clinical Global Impression of Change (CGI-C) [As per respiratory event on Day 10 and Day 20 post-event (up to approximately 2.5 years)]
- Percentage of Participants Within 3rd Percentile of Normal Range for Weight-to-Age at 72 Weeks of Risdiplam Treatment [Baseline, Week 72]
- Percentage of Participants Within 3rd Percentile of Normal Range for Length/Height-to-Age at 72 Weeks of Risdiplam Treatment [Baseline, Week 72]
- Percentage of Participants Within 3rd Percentile of Normal Range for Weight-to-Length/Height at 72 Weeks of Risdiplam Treatment [Baseline, Week 72]
- Number of Respiratory-Related Hospitalizations [Up to 72 weeks]
- Percentage of Participants With Adverse Events [Up to 72 weeks]
- Percentage of Participants With Serious Adverse Events [Up to 72 weeks]
- Percentage of Participants With Treatment Discontinuation Due to Adverse Events [Up to 72 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
<2 years of age at the time of informed consent
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Confirmed diagnosis of 5q-autosomal recessive SMA
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Confirmed presence of two SMN2 gene copies
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Administration of onasemnogene abeparvovec pre-symptomatically or post-symptomatically
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Has received onasemnogene abeparvovec for SMA no less than 3 months, but not more than 7 months, prior to enrollment
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Has, in the opinion of the investigator, not experienced clinically significant decline in function from the time of onasemnogene abeparvovec administration
Exclusion Criteria:
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Treatment with investigational therapy prior to initiation of study treatment
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Any unresolved standard-of-care laboratory abnormalities per the onasemnogene abeparvovec prescribing information
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Concomitant or previous administration of a SMN2-targeting antisense oligonucleotide or SMN2 splicing modifier either in a clinical study or as part of medical care
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Requiring invasive ventilation or tracheostomy
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Requiring awake non-invasive ventilation or with awake hypoxemia (SaO2 <95%) with or without ventilator support
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Presence of feeding tube and/or an OrSAT score of 0
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Hospitalization for pulmonary event within the last 2 months, or any planned hospitalization at the time of screening
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Any major illness requiring hospitalization within 1 month before the screening examination or any febrile illness within 1 week prior to screening and up to first dose administration.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BN44620
- 2023-504508-26-00