Evaluating risdiplam for young children with spinal muscular atrophy after gene therapy

A Phase IV Open-Label Study Evaluating the Effectiveness and Safety of Risdiplam Administered as an Early Intervention in Pediatric Patients With Spinal Muscular Atrophy After Gene Therapy

This study is testing if the medication risdiplam can help young children with spinal muscular atrophy feel better after they have received a specific gene therapy.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 3 Months to 24 Months
• Sex: All
• Sponsor: Hoffmann-La Roche (industry)
• Locations: 16 sites (Little Rock, Arkansas and 15 other locations)
• Trial ID: NCT05861986 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm clinical study assesses the effectiveness and safety of risdiplam as an early intervention in pediatric patients under 2 years old diagnosed with spinal muscular atrophy (SMA) who have received onasemnogene abeparvovec. The study focuses on children with two copies of the SMN2 gene and aims to determine if risdiplam can improve outcomes following gene therapy. Participants must have received the gene therapy within a specific time frame and not shown significant functional decline since treatment.

Who should consider this trial

Good fit: Ideal candidates are children under 2 years of age with a confirmed diagnosis of SMA and two copies of the SMN2 gene who have previously received onasemnogene abeparvovec.

Not a fit: Patients requiring invasive ventilation or tracheostomy, or those who have received other SMN2-targeting therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance the treatment outcomes for young children with spinal muscular atrophy, potentially improving their quality of life.

How similar studies have performed: Other studies have shown promise in using risdiplam for SMA, indicating a potential for success in this approach.

Eligibility criteria

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.

Where this trial is running

Little Rock, Arkansas and 15 other locations

• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States (RECRUITING)
• Children's Hospital of Colorado — Aurora, Colorado, United States (RECRUITING)
• University of Florida Pediatrics — Gainesville, Florida, United States (RECRUITING)
• Children's Healthcare of Atlanta Center for Advanced Pediatrics — Atlanta, Georgia, United States (RECRUITING)
• Ann and Robert H. Lurie Children Hospital of Chicago — Chicago, Illinois, United States (NOT_YET_RECRUITING)
• Helen DeVos Children's Hospital at Spectrum Health — Grand Rapids, Michigan, United States (RECRUITING)
• Columbia University Medical Center — New York, New York, United States (RECRUITING)
• Children'S Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (RECRUITING)
• The University of Texas Southwestern Medical Center at Dallas — Dallas, Texas, United States (RECRUITING)
• Cook Children's Jane and John Justin Neurosciences Center — Fort Worth, Texas, United States (RECRUITING)
• Children's Hospital of the King's Daughter — Norfolk, Virginia, United States (RECRUITING)
• Charité - Universitätsmedizin Berlin SPZ Abteilung Neuropaediatrie — Berlin, Germany (RECRUITING)
• UKGM Standort Gießen — Giessen, Germany (RECRUITING)
• Uniwersyteckie Centrum Kliniczne — Uniwersyteckie Centrum Kliniczne, Poland (RECRUITING)
• Instytut Pomnik Centrum Zdrowia Dziecka — Warsaw, Poland (RECRUITING)
• Great Ormond Street Hospital For Children — London, United Kingdom (RECRUITING)

Study contacts

• Study coordinator: Reference Study ID Number: BN44620 https://forpatients.roche.com/

Conditions: Muscular Atrophy, Spinal