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 (HINALEA 2)

• ClinicalTrials.gov Identifier: NCT05861999
• Recruitment Status: Recruiting
• First Posted: May 17, 2023
• Last Update Posted: May 13, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Muscular Atrophy, Spinal	Drug: risdiplam	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: June 30, 2024
• Estimated Primary Completion Date: January 31, 2027
• Estimated Study Completion Date: March 31, 2028

Arms and Interventions

Arm	Intervention/treatment
Experimental: Risdiplam; Participants will receive risdiplam orally once daily for 72 weeks (Treatment Period). The Treatment Period will be followed by a 1-year Treatment Extension Period for a total study duration of 120 weeks (approximately 2.5 years) for each participant enrolled.	Drug: risdiplam; Participants will receive risdiplam orally at the currently approved dose. The dose should be adapted for weight and age.; Other Name: RO7034067

Outcome Measures

Primary Outcome Measures :

1. 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 :

1. Percentage of Participants With Adverse Events [ Time Frame: Up to 120 weeks ]
2. Percentage of Participants With Serious Adverse Events [ Time Frame: Up to 120 weeks ]
3. Percentage of Participants With Treatment Discontinuation Due to Adverse Events [ Time Frame: Up to 120 weeks ]

Other Outcome Measures:

1. 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 [ Time Frame: From baseline up to Week 120 ]
2. 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 [ Time Frame: From baseline up to Week 120 ]
3. Change from Baseline in the Raw Score of BSID-III Gross Motor Score Over Time Under Risdiplam Treatment [ Time Frame: From baseline up to Week 120 ]
4. 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 [ Time Frame: From baseline up to Week 120 ]
5. 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 [ Time Frame: From baseline up to Week 120 ]
6. Change in World Health Organization (WHO) Motor Milestone Achievement at 72 Weeks of Risdiplam Treatment and Over Time [ Time Frame: From baseline up to Week 120 ]
7. Percentage of Participants With Improvement or No Change in Respiratory Illness as Assessed by Clinical Global Impression of Change (CGI-C) [ Time Frame: As per respiratory event on Day 10 and Day 20 postevent (up to Week 120) ]
8. Percentage of Participants Within 3rd Percentile of Normal Range for Weight-to-Age at 72 Weeks of Risdiplam Treatment and Over Time [ Time Frame: From baseline up to Week 120 ]
9. Percentage of Participants Within 3rd Percentile of Normal Range for Length/Height-to-Age at 72 Weeks of Risdiplam Treatment and Over Time [ Time Frame: From baseline up to Week 120 ]
10. Percentage of Participants Within 3rd Percentile of Normal Range for Weight-to-Length/Height at 72 Weeks of Risdiplam Treatment and Over Time [ Time Frame: From baseline up to Week 120 ]
11. Number of Respiratory-Related Hospitalizations During the 72-Week Risdiplam Treatment and Over Time [ Time Frame: Up to 120 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 3 Months to 24 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 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.

Contacts and Locations

Contacts

Contact: Reference Study ID Number: BN44621 https://forpatients.roche.com/; 888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

Locations

United States, Arkansas

University of Arkansas for Medical Sciences; Recruiting

Little Rock, Arkansas, United States, 72103

United States, California

Valley Children's Hospital; Recruiting

Madera, California, United States, 93636

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT05861999
• Other Study ID Numbers: BN44621; 2023-505161-81-00 ( Registry Identifier: EU CT number )
• First Posted: May 17, 2023
• Last Update Posted: May 13, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: This clinical trial evaluates treatment of a rare genetic disease in a small cohort of participants. No data is planned to be shared in order to protect and maintain participant privacy/confidentiality.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Muscular Atrophy; Muscular Atrophy, Spinal; Atrophy; Pathological Conditions, Anatomical; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Spinal Cord Diseases; Central Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases; Risdiplam; Neuromuscular Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs