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)

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 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.

Study Overview

• Status: Recruiting
• Conditions: Muscular Atrophy, Spinal
• Intervention / Treatment: Drug: risdiplam

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 4

Contacts and Locations

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

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72103
      • Recruiting
      • University of Arkansas for Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: RO7034067

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Adverse Events	Up to 120 weeks
Percentage of Participants With Serious Adverse Events	Up to 120 weeks
Percentage of Participants With Treatment Discontinuation Due to Adverse Events	Up to 120 weeks

Other Outcome Measures

Outcome Measure	Time Frame
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
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
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
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
Change in World Health Organization (WHO) Motor Milestone Achievement at 72 Weeks of Risdiplam Treatment and Over Time	From baseline up to Week 120
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
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
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
Number of Respiratory-Related Hospitalizations During the 72-Week Risdiplam Treatment and Over Time	Up to 120 weeks
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)
Change from Baseline in the Raw Score of BSID-III Gross Motor Score Over Time Under Risdiplam Treatment	From baseline up to Week 120

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: May 8, 2023
• First Submitted That Met QC Criteria: May 8, 2023
• First Posted (Actual): May 17, 2023

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy; Atrophy; Muscular Atrophy, Spinal; Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Risdiplam
• Other Study ID Numbers: BN44621; 2023-505161-81-00 (Registry Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No