A Study Evaluating the Effectiveness and Safety of Risdiplam Administered as an Early Intervention in Pediatric Participants With Spinal Muscular Atrophy After Gene Therapy
Risdiplam: Participants will receive risdiplam orally at the currently approved dose. The dose should be adapted for weight and age.
Study 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.
Eligibility
Sex
ALL
Min age
3 Months
Max age
24 Months
Healthy volunteers
No
Inclusion Criteria:
* \<2 years of age at the time of informed consent
* Confirmed diagnosis of 5q-autosomal recessive SMA, including genetic confirmation of homozygous deletion or compound heterozygosity predictive of loss of function of the Survival of Motor Neuron 1 (SMN1) gene
* Confirmed presence of two SMN2 gene copies as documented through laboratory testing
* Administration of onasemnogene abeparvovec pre-symptomatically or post-symptomatically
* Has received onasemnogene abeparvovec for SMA no less than 13 weeks, but not more than months 30 weeks, prior to enrollment
* If treated with risdiplam prior to onasemnogene abeparvovec, risdiplam treatment must not have exceeded 3 weeks and must be discontinued 1 day prior to onasemnogene abeparvovec administration
* Has, in the opinion of the investigator, not experienced clinically significant decline in function from the time of onasemnogene abeparvovec administration
Exclusion Criteria:
* Previous or current enrolment in investigational study prior to initiation of study treatment
* Any unresolved standard-of-care laboratory abnormalities per the onasemnogene abeparvovec prescribing information
* Concomitant or previous administration of an SMN2-targeting antisense oligonucleotide
* Concomitant or previous use of an anti-myostatin agent
* Participants requiring invasive ventilation or tracheostomy
* Participants requiring awake non-invasive ventilation or with awake hypoxemia (Arterial Oxygen Saturation \[SaO2\] \<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.
Primary outcome measure(s)
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 The BSID-III is a standardized assessment commonly used to evaluate developmental functioning of infants and young children between 1 month and 42 months of age. The gross motor scale measures the movement of the limbs and torso. Items assess static positioning (e.g., sitting, standing); dynamic movement, including locomotion and coordination; balance; and motor planning. The gross motor scale consists of 72 items scored at 0 (unable to perform) or 1 (criteria for item achieved). A higher raw score indicates improvement.
Trial sites (16)
Facility
City
Region
Status
University of Arkansas for Medical Sciences
Little Rock
Arkansas
Recruiting
Children's Hospital of Colorado
Aurora
Colorado
Recruiting
University of Florida Pediatrics
Gainesville
Florida
Recruiting
Children's Healthcare of Atlanta Center for Advanced Pediatrics
Atlanta
Georgia
Recruiting
Ann and Robert H. Lurie Children Hospital of Chicago
Chicago
Illinois
Recruiting
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids
Michigan
Recruiting
Columbia University Medical Center
New York
New York
Recruiting
Children'S Hospital of Philadelphia
Philadelphia
Pennsylvania
Recruiting
The University of Texas Southwestern Medical Center at Dallas
Dallas
Texas
Recruiting
Cook Children's Jane and John Justin Neurosciences Center
Fort Worth
Texas
Recruiting
Children's Hospital of the King's Daughter
Norfolk
Virginia
Withdrawn
Charité - Universitätsmedizin Berlin SPZ Abteilung Neuropaediatrie
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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