Evaluating risdiplam for children with spinal muscular atrophy after gene therapy

A Phase IV Open-Label Study Evaluating the Effectiveness and Safety of Risdiplam Administered in Pediatric Patients With Spinal Muscular Atrophy Who Experienced a Plateau or Decline in Function After Gene Therapy

This study is testing if the medication risdiplam can help young children with spinal muscular atrophy who have already had gene therapy but are not getting better.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 3 Months to 24 Months
• Sex: All
• Sponsor: Hoffmann-La Roche (industry)
• Locations: 19 sites (Little Rock, Arkansas and 18 other locations)
• Trial ID: NCT05861999 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm clinical study aims to assess the effectiveness and safety of risdiplam in pediatric patients under 2 years old who have spinal muscular atrophy (SMA) and have previously received gene therapy with onasemnogene abeparvovec. The study focuses on children who have experienced a plateau or decline in their functional abilities after the gene therapy. Participants will be monitored for changes in their swallowing and other motor functions over the course of the study. The goal is to determine if risdiplam can provide additional benefits in this specific patient population.

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 shown a plateau or decline in function after receiving onasemnogene abeparvovec.

Not a fit: Patients who have unresolved laboratory abnormalities or have received other SMN2-targeting therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve functional outcomes for young patients with spinal muscular atrophy who have not responded adequately to prior gene therapy.

How similar studies have performed: While this approach is novel in the context of post-gene therapy treatment for SMA, similar studies have shown promise in evaluating the effectiveness of risdiplam in other patient populations.

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 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.
* In the opinion of the investigator, has demonstrated a plateau or decline in function post-gene therapy (with a duration of 26 weeks or less) documented by 2 individual time points in the functions as follows: swallowing AND one additional function/ability (respiratory, motor function, other) per appropriate expectation.

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
* 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 18 other locations

• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States (RECRUITING)
• Valley Children's Hospital — Madera, California, United States (RECRUITING)
• Stanford Univ Medical Center — Palo Alto, California, 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)
• Helen DeVos Children's Hospital at Spectrum Health — Grand Rapids, Michigan, United States (RECRUITING)
• Children'S Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (RECRUITING)
• University of Texas Southwestern Medical Center — Dallas, 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)
• Soroka Medical Center — Beersheba, Israel (RECRUITING)
• Schneider Children's Medical Center of Israel — Petah Tikva, Israel (RECRUITING)
• Sourasky MC, Dana-Dwek Children's Hospital — Tel Aviv, Israel (RECRUITING)
• Uniwersyteckie Centrum Kliniczne — Gdansk, Poland (RECRUITING)
• Instytut Pomnik Centrum Zdrowia Dziecka — Warsaw, Poland (RECRUITING)
• Sidra Medicine — Al Rayyan, Qatar (RECRUITING)
• Great Ormond Street Hospital For Children — London, United Kingdom (RECRUITING)

Study contacts

• Study coordinator: Reference Study ID Number: BN44621 https://forpatients.roche.com/

Conditions: Muscular Atrophy, Spinal