A Study of Risdiplam in Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy

NCT03779334 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: BN407032018-002087-122023-506009-20-00
• Study Type: interventional
• Target: 26
• Locations: 7 countries
• Sites: 7

Brief Summary

A global study of oral risdiplam in pre-symptomatic participants with spinal muscular atrophy (SMA).

Conditions

Muscular Atrophy, Spinal

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Two Copies of the Survival Motor Neuron (SMN) 2 Gene (Excluding the Known SMN2 Gene Modifier Mutation c.859G>C) and Baseline Compound Muscle Action Potential (CMAP) >=1.5 Millivolt (mV) Who Are Sitting Without Support

  The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Gross Motor Scale is a commonly used measure of infant and toddler development (0 to 42 months). The normed-scores derived from the BSID-III are used in clinical practice to detect infants with developmental delays, as well as to evaluate developmental progress and the impact of therapeutic interventions. The gross motor scale consists of 72 items scored at 0 (unable to perform the activity) or 1 (criteria for item achieved). Item 22, "sits without support for 5 seconds", is not considered achieved if the infant sits alone for less than 5 seconds before losing balance and falling over, or if the infant uses his or her arms to prop him- or herself up. 90% CI for one sample binomial was computed using Clopper-Pearson (exact) method. An exact binomial test was performed. If the lower limit of the two-sided 90% CI was above the 5% threshold, the primary objective of the study was considered achieved.

  At Month 12

Secondary Outcomes (27)

• Percentage of Participants Developing Clinically Manifested SMA

  At Month 12 and 24

• Time to Permanent Ventilation and/or Death

  Up to 7 years

• Percentage of Participants Who Are Alive Without Permanent Ventilation

  At Month 12 and 24

• Percentage of Participants Alive

  At Month 12 and 24

• Percentage of Participants Who Achieve the Attainment Level of the Motor Milestones as Assessed in the Hammersmith Infant Neurological Examination-2 (HINE-2)

  At Month 12 and 24

Study Arms (1)

Open-label Risdiplam

EXPERIMENTAL

Participants will be enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range.

Drug: Risdiplam

Interventions

Risdiplam DRUG

Risdiplam will be administered orally.

Also known as: Evrysdi

Open-label Risdiplam

Eligibility Criteria

• Age: 1 Day - 6 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Males and females aged from birth (1 day) to 6 weeks (42 days) of age at the time of first dose (Day 1); a minimum age of 7 days at first dose is required for the first infant to be enrolled
• Gestational age of 37-42 weeks for singleton births; gestational age of 34-42 weeks for twins
• Body weight \>= 3rd percentile for age, using appropriate country-specific guidelines
• Genetic diagnosis of 5q-autosomal recessive SMA, including confirmation of homozygous deletion or compound heterozygosity predictive of loss of function of the SMN1 gene
• Absence of clinical signs or symptoms at screening (Day -42 to Day -2) or at baseline (Day -1) that are, in the opinion of the investigator, strongly suggestive of SMA
• Receiving adequate nutrition and hydration at the time of screening, in the opinion of the investigator
• Adequately recovered from any acute illness at baseline and considered well enough to participate in the study, in the opinion of the investigator
• Able and expected to be able to safely travel to the study site for the entire duration of the study and in accordance to the frequency of required study visits, in the opinion of the investigator
• Able to complete all study procedures, measurements, and visits, and the parent (or caregiver), in the opinion of the investigator, has adequately supportive psychosocial circumstances
• Parent (or caregiver) is willing to consider nasogastric, naso-jejunal, or gastrostomy tube placement during the study to maintain safe hydration, nutrition, and treatment delivery, if recommended by the investigator
• Parent (or caregiver) is willing to consider the use of non-invasive ventilation during the study, if recommended by the investigator

You may not qualify if:

• Concomitant or previous participation in any investigational drug or device study at any time
• Concomitant or previous administration of an SMN2-targeting antisense oligonucleotide, SMN2-splicing modifier, or gene therapy either in a clinical study or as part of medical care
• Presence of significant concurrent syndromes or diseases
• In the opinion of the investigator, inadequate venous or capillary blood access for the study procedures
• Requiring invasive ventilation, tracheostomy or awake non-invasive ventilation
• Awake hypoxemia (SaO2 \< 95%) with or without ventilator support
• Multiple or fixed contractures and/or hip subluxation or dislocation at birth
• Systolic blood pressure or diastolic blood pressure or heart rate considered to be clinically significant by the investigator
• Presence of clinically relevant ECG abnormalities before study drug administration; corrected QT interval using Bazett's method \> 460 ms; personal or family history (first degree relatives) of congenital long QT syndrome indicating a safety risk for patients as determined by the investigator. First-degree atrioventricular block or isolated right bundle branch block are allowed
• The infant (and the mother, if breastfeeding the infant) taking any inhibitor of CYP3A4 taken within 2 weeks, any inducer of CYP3A4 taken within 4 weeks, any OCT 2 and MATE substrates within 2 weeks and known FMO1 or FMO3 inhibitors or substrates
• Clinically significant abnormalities in laboratory test results
• Ascertained or presumptive hypersensitivity to risdiplam or to the constituents of its formulation
• Treatment with oral salbutamol or another beta-2 adrenergic agonist taken orally for SMA is not allowed. Use of inhaled beta-2 adrenergic agonists is allowed
• Infants exposed to drugs with known retinal toxicity given to mothers during pregnancy (and lactation) should not be enrolled. Anticipated need for drugs known to cause retinal toxicity during the study.
• Diagnosis of ophthalmic diseases

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (7)

Nemours Children's Hospital

Orlando, Florida, 32837, United States

Location

Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia

Location

Chr de La Citadelle

Liège, 4000, Belgium

Location

Hospital das Clinicas - FMUSP_X

São Paulo, São Paulo, 05403-000, Brazil

Location

Szpital Gdanskiego Uniwersytetu Medycznego

Gda?sk, 80-952, Poland

Location

Russian Children Neuromuscular Center of Veltischev

Moscow, Moscow Oblast, 125412, Russia

Location

Kaohsiung Medical University Chung-Ho Hospital

Kaohsiung City, 807, Taiwan

Location

Related Publications (1)

• Finkel RS, Servais L, Vlodavets D, Zanoteli E, Mazurkiewicz-Beldzinska M, Jong YJ, Navas-Nazario A, Al-Muhaizea M, Araujo APQC, Nelson L, Wang Y, Jaber B, Gorni K, Kletzl H, Palfreeman L, Rabbia M, Summers D, Gaki E, Wagner KR, Fontoura P, Farrar MA, Bertini E; RAINBOWFISH Study Group. Risdiplam in Presymptomatic Spinal Muscular Atrophy. N Engl J Med. 2025 Aug 14;393(7):671-682. doi: 10.1056/NEJMoa2410120.

  PMID: 40802943 DERIVED

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

Risdiplam

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, single arm

Study Record Dates

• First Submitted: December 17, 2018
• First Posted: December 19, 2018
• Study Start: August 7, 2019
• Primary Completion: February 20, 2023
• Study Completion (Estimated): February 28, 2027
• Last Updated: April 8, 2026
• Results First Posted: March 5, 2024

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

RU (1); TW (1); BE (1); BR (1); US (1); AU (1); PL (1)