Clinical trial NCT05861986: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Muscular Atrophy, Spinal
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2023-05-17
Enrollment: 28
Sex: ALL
Minimum age (years): 3
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Baseline, Week 72
Secondary outcomes:
measure: Percentage of Participants With Adverse Events
timeFrame: Up to 120 weeks
measure: Percentage of Participants With Serious Adverse Events
timeFrame: Up to 120 weeks
measure: Percentage of Participants With Treatment Discontinuation Due to Adverse Events
timeFrame: Up to 120 weeks
Other outcomes:
measure: Change from Baseline in Bulbar/Swallowing Function Assessment as Measured by the Oral and Swallowing Abilities Tool (OrSAT) at 72 Weeks of Risdiplam Treatment and Over Time
timeFrame: From baseline up to Week 120
measure: Change in Swallowing Function Assessment as Measured by the Pediatric Functional Oral Intake Scale (p-FOIS) at 72 Weeks of Risdiplam Treatment and Over Time
timeFrame: From baseline up to Week 120
measure: Change from Baseline in the Raw Score of BSID-III Gross Motor Score Over Time Under Risdiplam Treatment
timeFrame: From baseline up to Week 120
measure: Percentage of Participants With a Gross Motor Index Between 80-109 as Measured by the Peabody Developmental Motor Scale, Third Edition (PDMS-3) at 72 Weeks of Risdiplam Treatment and Over Time
timeFrame: From baseline up to Week 120
measure: Percentage of Participants With a Fine Motor Index Between 80-109 as Measured by the PDMS-3 at 72 Weeks of Risdiplam Treatment and Over Time
timeFrame: From baseline up to Week 120
measure: Change in World Health Organization (WHO) Motor Milestone Achievement at 72 Weeks of Risdiplam Treatment and Over Time
timeFrame: From baseline up to Week 120
measure: Percentage of Participants With Improvement or No Change in Respiratory Illness as Assessed by Clinical Global Impression of Change (CGI-C)
timeFrame: As per respiratory event on Day 10 and Day 20 post-event (up to Week 120)
measure: Percentage of Participants Within 3rd Percentile of Normal Range for Weight-to-Age at 72 Weeks of Risdiplam Treatment and Over Time
timeFrame: From baseline up to Week 120
measure: Percentage of Participants Within 3rd Percentile of Normal Range for Length/Height-to-Age at 72 Weeks of Risdiplam Treatment and Over Time
timeFrame: From baseline up to Week 120
measure: Percentage of Participants Within 3rd Percentile of Normal Range for Weight-to-Length/Height at 72 Weeks of Risdiplam Treatment and Over Time
timeFrame: From baseline up to Week 120
measure: Number of Respiratory-Related Hospitalizations During the 72-Week Risdiplam Treatment and Over Time
timeFrame: Up to 120 weeks
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Gainesville
country: United States
facility: University of Florida Pediatrics
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta Center for Advanced Pediatrics
state: Georgia
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children Hospital of Chicago
state: Illinois
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital at Spectrum Health
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Philadelphia
country: United States
facility: Children'S Hospital of Philadelphia
state: Pennsylvania
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Jane and John Justin Neurosciences Center
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughter
state: Virginia
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin SPZ Abteilung Neuropaediatrie
city: Gießen
country: Germany
facility: UKGM Standort Gießen
city: Gda?sk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Warszawa
country: Poland
facility: Instytut Pomnik Centrum Zdrowia Dziecka
city: London
country: United Kingdom
facility: Great Ormond Street Hospital For Children
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: