Risdiplam for Presymptomatic Spinal Muscular Atrophy

(Rainbowfish Trial)

Not currently recruiting at 23 trial locations

Overseen By Reference Study ID Number: BN40703 https://forpatients.roche.com/

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Investigational drug use, Significant syndromes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 9 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an oral medication called risdiplam, which aims to treat spinal muscular atrophy (SMA) before symptoms appear. The goal is to determine if risdiplam can prevent or delay the onset of this genetic condition that weakens muscles over time. It targets newborns up to 6 weeks old with a confirmed genetic risk for SMA but no symptoms yet. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that participants do not take certain medications, such as inhibitors or inducers of CYP3A4, OCT 2 and MATE substrates, and known FMO1 or FMO3 inhibitors or substrates, within specific time frames before starting the study. If you or your infant are taking these medications, you may need to stop them before participating.

Is there any evidence suggesting that risdiplam is likely to be safe for humans?

Research has shown that risdiplam is generally safe for people with spinal muscular atrophy (SMA). One study found that the safety profile for infants without symptoms was similar to those with symptoms, indicating no unexpected safety issues in asymptomatic infants.

The RAINBOWFISH study observed infants taking risdiplam for two years. Results confirmed the treatment's safety, with no new safety concerns. While side effects can occur, they were manageable and similar to those in other SMA patients taking risdiplam.

Overall, evidence suggests that risdiplam remains consistently safe for different groups of SMA patients, including those without symptoms. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for spinal muscular atrophy?

Risdiplam is unique because it offers a new way to tackle spinal muscular atrophy (SMA) by being administered orally, which is a significant departure from existing treatments that often require injections or infusions. Most treatments for SMA focus on increasing the production of a protein called SMN, but Risdiplam stands out by being a small molecule that modifies RNA splicing to boost SMN protein levels throughout the body. Researchers are particularly excited about Risdiplam because it has the potential to reach a broader range of tissues, possibly leading to more comprehensive benefits for patients with SMA.

What evidence suggests that risdiplam might be an effective treatment for spinal muscular atrophy?

Research has shown that risdiplam, the treatment being studied in this trial, holds promise for treating spinal muscular atrophy (SMA), especially when started early. In studies, babies treated with risdiplam soon after birth demonstrated significant improvements in movement skills and survival without needing breathing support. Specifically, data from the RAINBOWFISH study highlighted that early treatment helps babies reach movement skills typical for their age. Other trials have shown that risdiplam improves movement in both children and adults with SMA. These results suggest that risdiplam effectively manages SMA, particularly if treatment begins before symptoms appear. ^{1 6 7 8 9}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for infants from birth to 6 weeks old with a genetic diagnosis of spinal muscular atrophy (SMA) but no symptoms yet. They must be able to travel safely for study visits, have supportive caregivers, and not require invasive ventilation. Infants should weigh in the normal range for their age and have been born after a full-term pregnancy.

Inclusion Criteria

Receiving adequate nutrition and hydration at the time of screening, in the opinion of the investigator

I can safely travel to the study site for all required visits.

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

Exclusion Criteria

I have received treatments targeting the SMN2 gene.

My baby or I (if breastfeeding) haven't taken specific drugs affecting liver enzymes recently.

I am not taking oral salbutamol or similar drugs for SMA, but I may use inhaled versions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive risdiplam orally once daily for 2 years

24 months

Open-label extension

Participants continue to receive risdiplam for at least 3 additional years

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 7 years

What Are the Treatments Tested in This Trial?

Interventions

• Risdiplam

Trial Overview The trial is testing an oral medication called Risdiplam on infants who are genetically diagnosed with SMA but haven't shown symptoms. The goal is to see if early treatment can prevent or lessen muscle weakness caused by SMA.

How Is the Trial Designed?

Group I: Open-label Risdiplam Experimental Treatment 1 Intervention

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

Risdiplam is already approved in United States, European Union, Brazil, China for the following indications:

Approved in United States as Evrysdi for:

• Spinal muscular atrophy (SMA) in patients 2 months of age and older

Approved in European Union as Evrysdi for:

• 5q-autosomal recessive SMA with a clinical diagnosis of SMA types 1, 2, or 3 or with one to four survival motor neuron 2 (SMN2) copies

Approved in Brazil as Evrysdi for:

• Spinal muscular atrophy (SMA)

Approved in China as Evrysdi for:

• Spinal muscular atrophy (SMA)

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

In a phase 3 study involving 180 patients aged 2-25 with type 2 or non-ambulant type 3 spinal muscular atrophy, risdiplam significantly improved motor function compared to placebo, with a treatment difference of 1.55 points on the Motor Function Measure at 12 months (p=0.016).

While risdiplam was generally well-tolerated, it was associated with a higher incidence of certain adverse events, such as pyrexia and diarrhea, compared to placebo, but serious adverse events were similar between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial. Mercuri, E., Deconinck, N., Mazzone, ES., et al.[2022]

Risdiplam (Evrysdi®) is the first oral medication approved for treating spinal muscular atrophy (SMA) in patients aged 2 months and older, specifically targeting the production of the SMN protein essential for motor function.

In phase 2/3 clinical trials, risdiplam significantly improved motor function in infants with SMA type 1 and patients aged 2-25 years with SMA types 2 or 3, with benefits maintained for up to 2 years, and it was generally well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risdiplam: A Review in Spinal Muscular Atrophy. Paik, J.[2022]

Risdiplam (Evrysdi™) is an oral medication that modifies RNA splicing to enhance the production of functional SMN protein, addressing the deficiency caused by spinal muscular atrophy (SMA).

In August 2020, risdiplam received FDA approval for treating SMA in patients as young as 2 months old, and it is currently in the pre-registration phase in several countries, indicating its potential global impact on SMA treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risdiplam: First Approval. Dhillon, S.[2021]

Risdiplam is the first oral medication approved for spinal muscular atrophy (SMA) and has shown disease-modifying potential, acting as a splicing modifier for the SMN2 gene, which is crucial for motor neuron survival.

Clinical trials have demonstrated risdiplam's efficacy across SMA Types 1, 2, and 3, with a satisfactory safety profile, although its comparative effectiveness against other approved SMA treatments remains to be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risdiplam: an investigational survival motor neuron 2 (SMN2) splicing modifier for spinal muscular atrophy (SMA). Markati, T., Fisher, G., Ramdas, S., et al.[2022]

In a real-world study of 31 adult patients with spinal muscular atrophy types 2 and 3, risdiplam was well tolerated, with most patients reporting no side effects and some experiencing clinically meaningful improvements in motor function and quality of life.

The treatment not only stabilized motor functions but also led to unexpected benefits such as weight gain and improved appetite in a third of the patients, highlighting the need for monitoring effects beyond just neuromuscular outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risdiplam Real World Data - Looking Beyond Motor Neurons and Motor Function Measures. Sitas, B., Hancevic, M., Bilic, K., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40802943/

Risdiplam in Presymptomatic Spinal Muscular Atrophy Secondary outcomes that were assessed over a period of 24 months included survival, ventilatory support, motor milestones, the development of ...

2. evrysdi-hcp.com evrysdi-hcp.com/efficacy/results-in-presymptomatic-sma.html

Presymptomatic SMA Efficacy Results in Clinical Trials & Studies Find information about the clinical trial data from the RAINBOWFISH study of Evrysdi® (risdiplam) for infants with presymptomatic spinal muscular atrophy ...

3. evrysdi.com evrysdi.com/results-with-evrysdi/results-in-adults-and-children.html

Powerful results in adults and children with Type 2 and 3 ... Adults and children improved their motor skills and upper limb function when taking Evrysdi, an at-home treatment. SUNFISH is a 2-part, placebo-controlled ...

4. stjude.org stjude.org/media-resources/news-releases/2025-medicine-science-news/clinical-trial-shows-newborns-with-spinal-muscular-atrophy-can-start-treatment-at-birth.html

Clinical trial shows newborns with spinal muscular atrophy ... “We demonstrated in this study that with treatment shortly after birth, risdiplam maintained a good safety profile and generated a favorable ...

5. evrysdi-hcp.com evrysdi-hcp.com/efficacy/results-in-infantile-onset-sma.html

Infantile-Onset SMA Efficacy Results in Clinical Trials & Studies Find information about the clinical trial data from the FIREFISH study of Evrysdi® (risdiplam) for infantile-onset (Type 1) spinal muscular atrophy (SMA).

6. neurology.org neurology.org/doi/10.1212/WNL.0000000000205694

RAINBOWFISH: Primary Efficacy and Safety Data in ... Objective:To assess the efficacy and safety of risdiplam (EVRYSDI®) in infants with presymptomatic spinal muscular atrophy (SMA).

7. evrysdi-hcp.com evrysdi-hcp.com/efficacy/results-in-previously-treated-sma.html

Safety Results in Previously-Treated SMA, Clinical Trial Results Find information about the clinical trial data from the JEWELFISH study of Evrysdi® (risdiplam) for patients with Type 1, 2, or 3 SMA.

8. evrysdi.com evrysdi.com/

Evrysdi® (risdiplam) | Spinal Muscular Atrophy (SMA ... The safety profile of presymptomatic infants is consistent with the safety profile for symptomatic SMA patients treated with Evrysdi in clinical studies.

9. mdaconference.org mdaconference.org/abstract-library/rainbowfish-2-year-efficacy-and-safety-data-in-risdiplam-treated-infants-with-presymptomatic-spinal-muscular-atrophy-sma/

RAINBOWFISH: 2-year efficacy and safety data in risdiplam ... This analysis assesses the efficacy and safety of risdiplam in infants with presymptomatic SMA after 2 years of treatment. Results. Twenty-three infants ...