A 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

Muscular Atrophy, Spinal Clinical Trial

— HINALEA 2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05861999
• Other study ID #: BN44621
• Secondary ID: 2023-505161-81-0
• Status: Recruiting
• Phase: Phase 4
• Start date: June 30, 2024
• Est. completion date: March 31, 2028

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BN44621 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, single-arm, multicenter clinical study to evaluate the effectiveness and safety of risdiplam administered in pediatric participants with SMA and 2 SMN2 copies who previously received onasemnogene abeparvovec and experience a plateau or decline in function. Participants to be enrolled are children <2 years of age genetically diagnosed with SMA.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: March 31, 2028
• Est. primary completion date: January 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 24 Months

Eligibility

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 prior to enrollment

• In the opinion of the investigator, has demonstrated a plateau or decline in function post-gene therapy (with a duration of 6 months 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:

• 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

• 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.

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal

Intervention

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

Locations

Country	Name	City	State
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Valley Children's Hospital	Madera	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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		From baseline up to Week 120
Other	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		From baseline up to Week 120
Other	Change from Baseline in the Raw Score of BSID-III Gross Motor Score Over Time Under Risdiplam Treatment		From baseline up to Week 120
Other	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		From baseline up to Week 120
Other	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		From baseline up to Week 120
Other	Change in World Health Organization (WHO) Motor Milestone Achievement at 72 Weeks of Risdiplam Treatment and Over Time		From baseline up to Week 120
Other	Percentage of Participants With Improvement or No Change in Respiratory Illness as Assessed by Clinical Global Impression of Change (CGI-C)		As per respiratory event on Day 10 and Day 20 postevent (up to Week 120)
Other	Percentage of Participants Within 3rd Percentile of Normal Range for Weight-to-Age at 72 Weeks of Risdiplam Treatment and Over Time		From baseline up to Week 120
Other	Percentage of Participants Within 3rd Percentile of Normal Range for Length/Height-to-Age at 72 Weeks of Risdiplam Treatment and Over Time		From baseline up to Week 120
Other	Percentage of Participants Within 3rd Percentile of Normal Range for Weight-to-Length/Height at 72 Weeks of Risdiplam Treatment and Over Time		From baseline up to Week 120
Other	Number of Respiratory-Related Hospitalizations During the 72-Week Risdiplam Treatment and Over Time		Up to 120 weeks
Primary	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
Secondary	Percentage of Participants With Adverse Events		Up to 120 weeks
Secondary	Percentage of Participants With Serious Adverse Events		Up to 120 weeks
Secondary	Percentage of Participants With Treatment Discontinuation Due to Adverse Events		Up to 120 weeks