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

Official title

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

Overview

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.

Interventions

• Drug Risdiplam
  Participants will receive risdiplam orally at the currently approved dose. The dose should be adapted for weight and age.

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 [Time frame: Baseline, Week 72]

Secondary outcome measures (3)

• Percentage of Participants With Adverse Events [Time frame: Up to 120 weeks]
• Percentage of Participants With Serious Adverse Events [Time frame: Up to 120 weeks]
• Percentage of Participants With Treatment Discontinuation Due to Adverse Events [Time frame: Up to 120 weeks]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 11 centers

• University of Arkansas for Medical Sciences — Little Rock
• Children's Hospital of Colorado — Aurora
• University of Florida Pediatrics — Gainesville
• Children's Healthcare of Atlanta Center for Advanced Pediatrics — Atlanta
• Ann and Robert H. Lurie Children Hospital of Chicago — Chicago
• Helen DeVos Children's Hospital at Spectrum Health — Grand Rapids
• Columbia University Medical Center — New York
• Children'S Hospital of Philadelphia — Philadelphia
• … and 3 more centers

Germany · 2 centers

• Charité - Universitätsmedizin Berlin SPZ Abteilung Neuropaediatrie — Berlin
• UKGM Standort Gießen — Giessen

Poland · 2 centers

• Uniwersyteckie Centrum Kliniczne — Uniwersyteckie Centrum Kliniczne
• Instytut Pomnik Centrum Zdrowia Dziecka — Warsaw

United Kingdom · 1 center

• Great Ormond Street Hospital For Children — London

Identifiers

NCT: NCT05861986 · BN44620 · 2023-504508-26-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗