Risdiplam for Spinal Muscular Atrophy

(Jewelfish Trial)

Recruiting at 45 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must be taking: Nusinersen, Olesoxime, AVXS-101

Must not be taking: Chloroquine, Hydroxychloroquine, Retigabin, Vigabatrin

Disqualifiers: Unstable diseases, Drugs of abuse, 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

174 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a drug called risdiplam for treating individuals with Spinal Muscular Atrophy (SMA). It targets those who have previously participated in certain SMA studies or used treatments like nusinersen, olesoxime, or AVXS-101. The trial aims to understand how the body processes risdiplam and its effects over time. Individuals with a confirmed diagnosis of SMA who have used the specified treatments may be suitable for this study. Participants will take risdiplam daily for two years, with an option to continue for an additional three years. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to the development of a promising therapy.

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

Research has shown that risdiplam is generally safe for treating Spinal Muscular Atrophy (SMA). One study found that its safety profile aligns with previous trials, revealing no new safety concerns. This consistency indicates that the treatment affects people in a predictable manner. Another study observed risdiplam over five years and found it helped many children with SMA live longer, which is encouraging.

The treatment has been used by people of different ages and types of SMA and is usually well-tolerated, meaning most people did not experience serious side effects. These findings are important for anyone considering joining a clinical trial, as they suggest risdiplam is relatively safe based on past research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for SMA?

Unlike the standard treatments for Spinal Muscular Atrophy (SMA), which often involve gene therapy and injectable drugs, risdiplam stands out because it's taken orally. This makes it easier and less invasive for patients to use regularly. Researchers are excited about risdiplam because it works by increasing the production of a protein called SMN, which is crucial for muscle function, offering a new approach compared to traditional therapies. Its oral administration and distinct mechanism of action have the potential to significantly improve the quality of life for those with SMA.

What evidence suggests that risdiplam might be an effective treatment for Spinal Muscular Atrophy?

Research has shown that risdiplam effectively treats Spinal Muscular Atrophy (SMA). In earlier studies, both adults and children with SMA experienced improved motor skills and better use of their arms after taking risdiplam. Long-term results are encouraging, with 91% of children still alive after five years of treatment. This is significant because, without treatment, those with severe SMA often have a much shorter life expectancy. In this trial, participants will receive risdiplam, an oral medication that helps improve muscle function in people with SMA. These findings support risdiplam's potential to effectively manage SMA symptoms. ^{2 4 6 7 8}

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 adults, children, and infants with Spinal Muscular Atrophy who have been part of a previous study or treated with specific drugs. Women must not be pregnant and agree to contraception; men also need to use birth control. Participants should be well enough in the investigator's opinion, and young children may need feeding tubes or ventilation as recommended.

Inclusion Criteria

I have previously participated in the Moonfish study or have been treated with specific drugs for my condition.

I agree to not have sex or use birth control and not donate sperm.

Adequately recovered from any acute illness at the time of screening and considered well enough to participate in the opinion of the Investigator For women of childbearing potential: negative blood pregnancy test at screening, agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs for at least 28 days after the final dose of study drug

Exclusion Criteria

I have a history of cancer that is not considered cured.

I have previously used chloroquine, hydroxychloroquine, retigabin, vigabatrin, or thioridazine.

I have had an eye disease in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of risdiplam orally once daily

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment long-term

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Risdiplam

Trial Overview The trial tests Risdiplam's safety, tolerability, how it moves through and affects the body (PK/PD) in those with SMA previously enrolled in a related study or treated with certain other medications. It's an exploratory open-label study without comparison groups.

How Is the Trial Designed?

Group I: Risdiplam Experimental Treatment 1 Intervention

Participants will receive multiple doses of risdiplam orally once daily for 24 months. After 24-month treatment, participants will be offered the opportunity to enter the open-label extension (OLE) phase for 3 years.

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

Citations

1. 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 ...

2. roche.com roche.com/media/releases/med-cor-2024-06-07

Five-year data for Roche's Evrysdi show the majority of ... After five years of treatment, 91% of children were alive — without treatment, children with Type 1 SMA would not be expected to live past ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8567805/

Risdiplam for the Use of Spinal Muscular Atrophy - PMC Risdiplam is the first and only oral medication to be approved to treat SMA. As an SMN2 splicing modifier, it has provided stronger systemic therapies.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02908685

NCT02908685 | A Study to Investigate the Safety, ... A positive change from Baseline indicates improvement. MMRM analysis was performed based on primary efficacy hypothetical estimand, which included participants ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2589537025004699

Efficacy and safety of risdiplam in adults with 5q-associated ... Evaluation of risdiplam efficacy in 5q spinal muscular atrophy: a systematic comparison of electrophysiologic with clinical outcome measures.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38189761/

Risdiplam in Spinal Muscular Atrophy: Safety Profile and ... This study found a safety profile similar to clinical trials with no new safety concerns identified. With the restricted eligibility of onasemnogene ...

7. 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 ...

8. 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.