Troriluzole for Spinocerebellar Ataxia

Recruiting at 22 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Biohaven Pharmaceuticals, Inc.

Disqualifiers: Spasticity, Dystonia, Liver disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

299 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial team for guidance.

What data supports the effectiveness of the drug Troriluzole for Spinocerebellar Ataxia?

Research on riluzole, a component related to Troriluzole, has shown benefits in patients with cerebellar ataxias, suggesting potential effectiveness for similar conditions. Additionally, riluzole has demonstrated positive effects in neurodegenerative conditions like ALS, which may indicate its potential in treating spinocerebellar ataxia. ^{1 2 3 4 5}

Is Troriluzole safe for human use?

Riluzole, a drug similar to Troriluzole, has been studied for safety in humans and is generally considered to have an acceptable safety profile. Common side effects include nausea, vomiting, and dizziness, but these are often reversible and dose-dependent. Regular monitoring of liver function is recommended during treatment. ^{1 2 6 7 8}

What makes the drug Troriluzole unique for treating spinocerebellar ataxia?

Troriluzole is unique because it is a prodrug of riluzole, which means it is converted into riluzole in the body, potentially offering improved delivery and effectiveness. Riluzole has shown benefits in treating cerebellar ataxia by blocking glutamate release, a neurotransmitter that can be harmful in excess, and Troriluzole may enhance these effects. ^{2 3 4 9 10}

What is the purpose of this trial?

This trial is testing whether a medication called Troriluzole can help people with spinocerebellar ataxia by balancing a brain chemical to prevent damage. Troriluzole is related to riluzole, which has been shown to prolong survival and slow functional deterioration in patients with ALS.

Eligibility Criteria

Adults with spinocerebellar ataxia (SCA) types SCA1, SCA2, SCA3, SCA7, and SCA10 who can walk 8 meters unaided (devices okay), have a specific score on the f-SARA gait test, and are medically stable. Those with severe cognitive impairment or conditions that could affect their ataxia severity aren't eligible.

Inclusion Criteria

Your f-SARA total score is 3 or higher during screening.

I have or might have a specific type of hereditary ataxia (SCA1, SCA2, SCA3, SCA7, or SCA10).

I have been diagnosed with a specific type of hereditary ataxia (SCA1, SCA2, SCA3, SCA7, or SCA10).

Exclusion Criteria

You have severe muscle stiffness or uncontrollable muscle movements that could make it difficult for the SARA instrument to measure the severity of your ataxia.

I have liver disease or a history of bad reactions to medications due to my liver.

My memory and thinking skills test score is below 24.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Troriluzole or placebo for 48 weeks in a double-blind randomization phase

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment with open-label Troriluzole up to Week 192

192 weeks

Treatment Details

Interventions

• Placebos
• Troriluzole

Trial Overview The trial is testing Troriluzole (200mg daily) against a placebo over 48 weeks to see if it's more effective in treating symptoms of spinocerebellar ataxia. Participants will be randomly assigned to either the drug or placebo group.

Participant Groups

Group I: Troriluzole Experimental Treatment 1 Intervention

Randomization phase (Randomization through Week 48): Participants received starting dose of troriluzole 140 milligrams (mg) capsules orally once daily for first 4 weeks, followed by 200 mg once daily for the remaining 44 weeks of 48-week duration of the double-blind randomization phase. Open-label extension (OLE) phase (OLE Week 1 up to Week 192): Participants who were eligible and agreed to enroll in an OLE phase, will receive troriluzole 200 mg capsules orally once daily for 4 weeks in a blinded manner. After OLE Week 4, all participants will then receive open label troriluzole 200 mg up to Week 192.

Group II: Placebo Placebo Group 2 Interventions

Randomization phase (Randomization through Week 48): Participants received troriluzole matching placebo capsules orally once daily for 48 weeks duration of the double-blind randomization phase. OLE phase (Week 1 up to Week 192): Participants who were eligible and agreed to enroll in an OLE phase, will receive troriluzole 140 mg capsules orally once daily for the first 4 weeks in a blinded manner. After OLE Week 4, all participants will then receive open label troriluzole 200 mg up to Week 192.

Who Is Running the Clinical Trial?

Biohaven Pharmaceuticals, Inc.

Lead Sponsor

Trials

49

Recruited

30,100+

Findings from Research

In a case series of 13 patients with degenerative cerebellar ataxia, treatment with acetyl-DL-leucine (5 g/day) for one week led to significant improvements in motor function, as measured by the Scale for the Rating and Assessment of Ataxia (SARA), with a notable decrease in scores from 16.1 to 12.8.

Patients also reported enhanced quality of life during treatment, and importantly, no side effects were observed, suggesting a favorable risk-benefit profile for acetyl-DL-leucine in managing ataxic symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of acetyl-DL-leucine in patients with cerebellar ataxia: a case series. Strupp, M., Teufel, J., Habs, M., et al.[2021]

In a study of 153 ALS patients, riluzole was found to have an acceptable safety profile, with 50.3% experiencing adverse effects, primarily gastrointestinal issues, hepatotoxicity, and fatigue.

Riluzole's mechanism of action suggests it may also be beneficial for other neurodegenerative diseases related to glutamate excitotoxicity, warranting further investigation and monitoring for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse efects of riluzole (Rilutek) in the treatment of amyotrophic lateral sclerosis]. Roch-Torreilles, I., Camu, W., Hillaire-Buys, D.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study (RISCIS): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Rasagiline alone and in combination with riluzole prolongs survival in an ALS mouse model. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Riluzole in patients with hereditary cerebellar ataxia: a randomised, double-blind, placebo-controlled trial. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Effects of acetyl-DL-leucine in patients with cerebellar ataxia: a case series. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Treatment of cerebellar ataxia with 5-HT1A agonist. [2018]

6. France pubmed.ncbi.nlm.nih.gov

[Adverse efects of riluzole (Rilutek) in the treatment of amyotrophic lateral sclerosis]. [2013]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of riluzole on harmaline induced tremor and ataxia in rats: biochemical, histological and behavioral studies. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

[Tolerability of riluzole: a review of the literature]. [2013]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Cerebellar ataxia with anti-mGluR1 auto-antibody in a pediatric patient: A case report. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Riluzole in cerebellar ataxia: a randomized, double-blind, placebo-controlled pilot trial. [2019]