A Study Evaluating the Effectiveness and Safety of Risdiplam Administered as an Early Intervention in Pediatric Participants With Spinal Muscular Atrophy After Gene Therapy (HINALEA 1)

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

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.

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: BN44620 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charité - Universitätsmedizin Berlin SPZ Abteilung Neuropaediatrie
  • Giessen, Germany, 35392
    • Recruiting
    • UKGM Standort Gießen
• Poland
  • Uniwersyteckie Centrum Kliniczne, Poland, 80-952
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne
  • Warsaw, Poland, 04-730
    • Recruiting
    • Instytut Pomnik Centrum Zdrowia Dziecka
• United Kingdom
  • London, United Kingdom, WC1N 3JH
    • Recruiting
    • Great Ormond Street Hospital for Children
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72103
      • Recruiting
      • University of Arkansas for Medical Sciences
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital of Colorado
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida Pediatrics
  • Georgia
    • Atlanta, Georgia, United States, 30329-2309
      • Recruiting
      • Children's Healthcare of Atlanta Center for Advanced Pediatrics
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Not yet recruiting
      • Ann and Robert H. Lurie Children Hospital of Chicago
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Helen DeVos Children's Hospital at Spectrum Health
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • The University of Texas Southwestern Medical Center at Dallas
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Cook Children's Jane and John Justin Neurosciences Center
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Recruiting
      • Children's Hospital of The King's Daughter

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, 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.

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	Measure Description	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	The BSID-III is a standardized assessment commonly used to evaluate developmental functioning of infants and young children between 1 month and 42 months of age. The gross motor scale measures the movement of the limbs and torso. Items assess static positioning (e.g., sitting, standing); dynamic movement, including locomotion and coordination; balance; and motor planning. The gross motor scale consists of 72 items scored at 0 (unable to perform) or 1 (criteria for item achieved). A higher raw score indicates improvement.	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	Measure Description	Time Frame
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
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	The OrSAT is a validated assessment composed of a checklist of 12 questions assessing aspects of swallowing abilities thought to be clinically meaningful for a type 1 SMA population and developmentally appropriate for infants during the first months of life. Each item is graded with a score of 0 or 1, depending on the child's ability to perform the activity. As some items are age-dependent, the number of items to be used, and therefore the maximum score, changes with increasing age. In the infants younger than 6 months the maximum score is 7. For those between 6 and 9 months, maximum score is 10. For infants of 10 months or older, maximum total score is 12.	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	The p-FOIS is a 6-point scale that assesses feeding ability, 1= Nothing by mouth, 2= Tube dependent for all nutrition/hydration needs with minimal attempts at oral intake for experience and/or pleasure, 3= Tube dependent with consistent intake of food and/or fluid that meets some of the nutrition/hydration needs, 4= Total oral intake but special preparation required, e.g., thickened fluids, puréed diet (where not age-appropriate), 5= Total oral intake but requiring special conditions/modification, e.g., slow flow teat/side lying/pacing or specific food limitations, 6= Total, age-appropriate, oral intake with no restrictions. Higher score indicates higher level of function.	From baseline up to Week 120
Change from Baseline in the Raw Score of BSID-III Gross Motor Score Over Time Under Risdiplam Treatment	The BSID-III is a standardized assessment commonly used to evaluate developmental functioning of infants and young children between 1 month and 42 months of age. The gross motor scale measures the movement of the limbs and torso. Items assess static positioning (e.g., sitting, standing); dynamic movement, including locomotion and coordination; balance; and motor planning. The gross motor scale consists of 72 items scored at 0 (unable to perform) or 1 (criteria for item achieved). A higher raw score indicates improvement.	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	The PDMS-3 is used to assess gross- and fine-motor skills in children from birth to 5 years. The PDMS-3 has 3 composite scores: Total Motor (combined scores of the core subtests) and two domain composites (Gross Motor and Fine Motor). By combining the results of subtests, these composite scores are considered to have stronger and better indexes of performance and, therefore, more reliable and valid than the subtests. Score for composite indexes range from <70 (impaired or delayed) to >129 (gifted or very advanced). Score of 80-89 indicate below average and 90-109 indicate average skills.	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	The PDMS-3 is used to assess gross- and fine-motor skills in children from birth to 5 years. The PDMS-3 has 3 composite scores: Total Motor (combined scores of the core subtests) and two domain composites (Gross Motor and Fine Motor). By combining the results of subtests, these composite scores are considered to have stronger and better indexes of performance and, therefore, more reliable and valid than the subtests. Score for composite indexes range from <70 (impaired or delayed) to >129 (gifted or very advanced). Score of 80-89 indicate below average and 90-109 indicate average skills.	From baseline up to Week 120
Change in World Health Organization (WHO) Motor Milestone Achievement at 72 Weeks of Risdiplam Treatment and Over Time	The WHO motor milestones evaluate gross motor development and comprise the time windows of achievement for six gross motor milestones based on data derived from the WHO Multicenter Growth Reference Study (MGRS). The six gross motor milestones are as follows: sitting without support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone, and walking alone. A yes response indicates that the participant reached a particular development milestone.	From baseline up to Week 120
Percentage of Participants With Improvement or No Change in Respiratory Illness as Assessed by Clinical Global Impression of Change (CGI-C)	In a case of respiratory illness during the study, a range of clinical domain level items will be completed by the investigator, as needed. The CGI-C is a single item measure of change using seven response options: "Very much improved," "Much improved," "Minimally improved," "No change," "Minimally worse," "Much worse," and "Very much worse."	As per respiratory event on Day 10 and Day 20 post-event (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 (Actual): May 30, 2024
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029

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): May 4, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy, Spinal; Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Risdiplam
• Other Study ID Numbers: BN44620; 2023-504508-26-00 (Ctis: 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