Muscular Atrophy, SpinalPhase 2RainbowfishNCT03779334
A Study of Risdiplam in Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
A Phase 2 study testing Risdiplam in people with Muscular Atrophy, Spinal, run by Hoffmann-La Roche at 7 sites in 7 countries.
Trial summary
A global study of oral risdiplam in pre-symptomatic participants with spinal muscular atrophy (SMA). Read more about this study
- Who is it for?
- Ages 1 day to 6 weeks
- Conditions the study is for
- Muscular Atrophy, Spinal
- What is being tested?
- Risdiplam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 7 sitesin 7 countries
- Study dates
- 7 Aug 2019to 28 Feb 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 6 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
7 sites in 7 countries.
7 sites in 7 countries
Russia1 site
Russian Children Neuromuscular Center of Veltischev
Moscow, Moscow Oblast, 125412
Taiwan1 site
Kaohsiung Medical University Chung-Ho Hospital
Kaohsiung City, 807
About this study
Official title: An Open-Label Study of Risdiplam in Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
A global study of oral risdiplam in pre-symptomatic participants with spinal muscular atrophy (SMA).
Read the detailed description
The study is an open-label, single-arm, multicenter clinical study to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of risdiplam in infants aged from birth to 6 weeks who have been genetically diagnosed with SMA but are not yet presenting with symptoms. There will be a screening, treatment, open-label extension (OLE) and a follow-up. All participants will receive risdiplam orally once daily for 2 years followed by an OLE phase of at least 3 years and a follow-up (if applicable), for a total treatment duration of at least 5 years for each participant enrolled.
- Conditions
- Muscular Atrophy, Spinal
- Being tested
- Risdiplam
- Medical subject headings
- Muscular Atrophy, Spinal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RisdiplamDrug
Also called Evrysdi
Risdiplam will be administered orally.
| Study group | Role | What they receive |
|---|---|---|
| Open-label Risdiplam | Experimental | Participants will be enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range. Receives: Drug: Risdiplam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At Month 12
Secondary outcomes (27)
Percentage of Participants Developing Clinically Manifested SMA
Measured: At Month 12 and 24
Time to Permanent Ventilation and/or Death
Measured: Up to 7 years
Percentage of Participants Who Are Alive Without Permanent Ventilation
Measured: At Month 12 and 24
Percentage of Participants Alive
Measured: 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)
HINE-2 assessment includes head control, sitting, voluntary grasp, ability to kick, rolling, crawling, standing, and walking
Measured: At Month 12 and 24
Percentage of Participants With Two Copies of the SMN2 Gene Sitting Without Support for 5 Seconds (Independent of the CMAP Value at Baseline).
Assessed in Item 22 of the BSID-III Gross Motor Scale. The BSID-III 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.
Measured: At Month 12
Percentage of Participants Sitting Without Support for 5 Seconds
Assessed with BSID-III Gross Motor Scale
Measured: At Month 24
Percentage of Participants Sitting Without Support for 30 Seconds
Assessed with BSID-III Gross Motor Scale
Measured: At Month 12 and 24
Percentage of Participants Standing for at Least 3 Seconds
Assessed with BSID-III Gross Motor Scale
Measured: At Month 24
Percentage of Participants Walking (Takes at Least 3 Steps)
Assessed with BSID-III Gross Motor Scale
Measured: At Month 24
Percentage of Participants Demonstrating the Ability to Achieve a Scaled Score on BSID-III Gross Motor Subtests Within 1.5 Standard Deviations of Chronological Reference Standard
Assessed through BSID-III Gross Motor Scale
Measured: At Month 24 and 42
Change From Baseline Score in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale at Month 12
The CHOP-INTEND is a measure of motor function that was developed from the Test of Infant Motor Performance specifically for weak infants with neuromuscular disease. It consists of 16 items, where each item assesses a specific motor task (such as spontaneous movement of upper and lower extremity, hand grasping, rolling, head control, and others) graded on a scale of 0 to 4, where zero is no response and 4 is a complete response. A total score is calculated by summing the item scores (range 0 to 64) with lower scores indicating greater severity. A positive change from baseline indicates an improvement.
Measured: Baseline, Month 12
Percentage of Participants Who Achieve a Score of 40 or Higher, 50 or Higher, and 60 or Higher in the CHOP INTEND Motor Function Scale at Month 12
The CHOP-INTEND is a measure of motor function that was developed from the Test of Infant Motor Performance specifically for weak infants with neuromuscular disease. It consists of 16 items, where each item assesses a specific motor task (such as spontaneous movement of upper and lower extremity, hand grasping, rolling, head control, and others) graded on a scale of 0 to 4, where zero is no response and 4 is a complete response. A total score is calculated by summing the item scores (range 0 to 64) with lower scores indicating greater severity. Data are presented with a two-sided 90% Clopper-Pearson (exact) CI for the proportion.
Measured: At Month 12
Percentage of Participants Who Meet CHOP INTEND Stopping Criteria at Any Point
Measured: Up to Month 24
Change From Baseline in the Hammersmith Functional Motor Scale Expanded (HFMSE) Score
Measured: At Month 60
Number and Percentage of Participants Within 3rd Percentile of Normal Range for Weight-for-Age, Length/Height-for-Age and Weight-for-Length/Height
Based on the WHO Child Growth Standards (WHO 2019)
Measured: At Month 12, 24, 36, 48 and 60
Number and Percentage of Participants Within 3rd Percentile of Normal Range for Head Circumference-for-age
Based on the WHO Child Growth Standards (WHO 2019)
Measured: At Month 12 and 24
Change From Baseline Percentiles for Weight-for-age, Length/Height-for-age, and weight-for- Length/Height
Measured: At Month 12, 24, 36, 48 and 60
Change From Baseline Percentiles for Head Circumference- For-age
Measured: At Month 12 and 24
Change From Baseline in Chest Circumference
Measured: At Month 12 and 24
Ratio Between Chest and Head Circumferences
Measured: At Month 12 and 24
Percentage of Participants With the Ability to Swallow and to Feed Orally
Measured: At Month 12, 24, 36, 48 and 60
Change From Baseline in Compound Muscle Action Potential (CMAP) Amplitude
Measured by CMAP
Measured: At Month 12 and 24
Measurement of Pharmacodynamic Marker Levels in Blood
Measured: Day 1, 56, 196, 364, 728 and at early withdrawal
Percentage of Participants With Adverse Events
Adverse event severity is determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 (NCI CTCAE) v5
Measured: Up to 7 years
Ophthalmological Examination as Appropriate for Age
Measured: Up to 7 years
Plasma Concentration of Risdiplam and Its Metabolites to Characterize the PK Profile
Measured: Up to 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2018
- Study start7 Aug 2019
- Primary completion20 Feb 2023
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Muscular Atrophy, SpinalStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label, single arm
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03779334
- Sponsor's protocol ID
- BN40703
- Other IDs
- 2018-002087-12, 2023-506009-20-00, 2023, 2018
- Acronym
- Rainbowfish
- Status last verified
- Oct 2026
- First submitted
- 17 Dec 2018
- Last updated
- 8 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing
Publications
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.
PubMed 40802943