Risdiplam for Presymptomatic Spinal Muscular Atrophy

(Rainbowfish Trial)

Recruiting at 20 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

26 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Risdiplam for presymptomatic spinal muscular atrophy?

Risdiplam has been shown to improve motor function in patients with spinal muscular atrophy types 1, 2, and 3 by increasing the production of a crucial protein called SMN. It is the first oral drug approved for this condition and has demonstrated significant motor improvements in clinical trials, with benefits maintained for up to two years. ^{1 2 3 4 5}

Is Risdiplam safe for humans?

Risdiplam, also known as Evrysdi, has been generally well tolerated in clinical trials for spinal muscular atrophy, showing a favorable balance between benefits and risks. No new safety concerns have been reported in real-world data, indicating it is generally safe for human use. ^{1 2 3 4 5}

How is the drug risdiplam unique for treating spinal muscular atrophy?

Risdiplam is unique because it is the first oral drug for spinal muscular atrophy, making it more convenient than other treatments that require injections. It works by modifying the SMN2 gene to increase the production of a protein essential for muscle function, which is lacking in people with this condition. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing a medicine called risdiplam, which is taken by mouth. It aims to help infants who have a genetic diagnosis of spinal muscular atrophy (SMA) but are not yet showing symptoms. The medicine works by helping the body make more of a protein that muscles need to stay healthy. The goal is to see if early treatment can prevent or lessen the severity of SMA.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 (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]

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]

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]

References

1. England 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. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Risdiplam: First Approval. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. Netherlands pubmed.ncbi.nlm.nih.gov

Risdiplam Real World Data - Looking Beyond Motor Neurons and Motor Function Measures. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Risdiplam: an investigational survival motor neuron 2 (SMN2) splicing modifier for spinal muscular atrophy (SMA). [2022]