A Study Evaluating the Effectiveness and Safety of Risdiplam Administered as an Early Intervention in Pediatric Participants With Spinal Muscular Atrophy After Gene Therapy

Phase 4

Recruiting

• Conditions: Muscular Atrophy, Spinal
• Interventions: Drug: risdiplam

• Registration Number: NCT05861986
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-08
• Study First Submitted QC: 2023-05-08
• Study First Posted: 2023-05-17
• Study Start: 2024-05-30
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-16
• Last Update Posted: 2025-05-18
• Primary Completion: 2027-01-31
• Study Completion: 2028-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

• <2 years of age at the time of informed consent
• Confirmed diagnosis of 5q-autosomal recessive SMA
• Confirmed presence of two SMN2 gene copies
• Administration of onasemnogene abeparvovec pre-symptomatically or post-symptomatically
• Has received onasemnogene abeparvovec for SMA no less than 3 months, but not more than 7 months, prior to enrollment
• Has, in the opinion of the investigator, not experienced clinically significant decline in function from the time of onasemnogene abeparvovec administration

Exclusion Criteria

• Treatment with investigational therapy prior to initiation of study treatment
• Any unresolved standard-of-care laboratory abnormalities per the onasemnogene abeparvovec prescribing information
• 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
• Requiring invasive ventilation or tracheostomy
• Requiring awake non-invasive ventilation or with awake hypoxemia (SaO2 <95%) with or without ventilator support
• Presence of feeding tube and an OrSAT score of 0
• Hospitalization for pulmonary event within the last 2 months, or any planned hospitalization at the time of screening
• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Risdiplam	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Percentage of Participants With Serious Adverse Events	Up to 120 weeks
Percentage of Participants With Adverse Events	Up to 120 weeks
Percentage of Participants With Treatment Discontinuation Due to Adverse Events	Up to 120 weeks

Trial Locations

Locations (16)

Instytut Pomnik Centrum Zdrowia Dziecka; 🇵🇱 Warszawa, Poland

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Children's Hospital of Colorado; 🇺🇸 Aurora, Colorado, United States

University of Florida Pediatrics; 🇺🇸 Gainesville, Florida, United States

Children's Healthcare of Atlanta Center for Advanced Pediatrics; 🇺🇸 Atlanta, Georgia, United States

Ann and Robert H. Lurie Children Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

Helen DeVos Children's Hospital at Spectrum Health; 🇺🇸 Grand Rapids, Michigan, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Children'S Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

The University of Texas Southwestern Medical Center at Dallas; 🇺🇸 Dallas, Texas, United States

Cook Children's Jane and John Justin Neurosciences Center; 🇺🇸 Fort Worth, Texas, United States

Children's Hospital of the King's Daughter; 🇺🇸 Norfolk, Virginia, United States

Charité - Universitätsmedizin Berlin SPZ Abteilung Neuropaediatrie; 🇩🇪 Berlin, Germany

UKGM Standort Gießen; 🇩🇪 Gießen, Germany

Uniwersyteckie Centrum Kliniczne; 🇵🇱 Gda?sk, Poland

Great Ormond Street Hospital For Children; 🇬🇧 London, United Kingdom