What is the mechanism of action of this treatment?

The most common treatments for Spinocerebellar Ataxias (SCA) often focus on modulating glutamate activity, as excessive glutamate can lead to neurotoxicity and neuronal damage. Troriluzole, for example, is designed to reduce glutamate release and enhance its reuptake, thereby protecting neurons from excitotoxicity. This mechanism is crucial for SCA patients because it aims to slow down the progression of neurodegeneration and alleviate symptoms associated with the disease. By stabilizing glutamate levels, these treatments help maintain neuronal function and potentially improve motor coordination and quality of life for SCA patients.

What side effects are associated with this type of intervention?

Common treatments for Spinocerebellar Ataxias (SCAs) that involve glutamate modulation, such as Troriluzole, often have side effects including dizziness, nausea, fatigue, and elevated liver enzymes. Other possible side effects include gastrointestinal disturbances and, less commonly, respiratory issues. These side effects are generally mild to moderate, but it is important to discuss them with a healthcare provider for proper management.

What prior FDA approvals exist?

Currently, there are no FDA-approved treatments specifically for Spinocerebellar Ataxias (SCA). Research is ongoing to find effective therapies, including the study of Troriluzole, which modulates glutamate. This approach aims to address the neurodegenerative aspects of SCA by reducing excitotoxicity. Other treatments for SCA are generally symptomatic and may include physical therapy, speech therapy, and medications to manage specific symptoms, but none are curative.

What other types of research exist?

Promising novel alternatives to Troriluzole for Spinocerebellar Ataxias patients include gene therapies targeting specific genetic mutations, antisense oligonucleotides (ASOs) that can modulate gene expression, and neuroprotective agents like Riluzole derivatives. Additionally, therapies focusing on mitochondrial function and calcium channel blockers are being explored for their potential benefits in SCA treatment.

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Glutamate Modulator

Troriluzole for Spinocerebellar Ataxia

Phase 3

Waitlist Available

Research Sponsored by Biohaven Pharmaceuticals, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects with a known or suspected diagnosis of specific hereditary ataxias: SCA1, SCA2, SCA3, SCA7, and SCA10

Subjects with a known or suspected diagnosis of the following specific hereditary ataxias: SCA1, SCA2, SCA3, SCA6, SCA7, SCA8 and SCA10; currently only enrolling SCA 1, SCA2, SCA3, SCA7, and SCA10 (the cap has been met for SCA6 and SCA8 (on May 31, 2019));

Must not have

MMSE score <24

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to week 48

Awards & highlights

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While not specified here, potential side effects for Troriluzole may include nausea, dizziness, fatigue or other common drug-related reactions. The exact side effects will be monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

Select...

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

Select...

My condition has been genetically confirmed by a certified lab, or I have a family member with a confirmed diagnosis and I am willing to undergo genetic testing.

Select...

I can walk 8 meters by myself, but I can use a cane or other aid if needed.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

My memory and thinking skills test score is below 24.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to week 48

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to week 48

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to week 48 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change from Baseline in the total score of the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) after 48 weeks of treatment.

Secondary study objectives

1. Change from baseline in Patient Impression of Function and Activities of Daily Living Scale (PIFAS) score at Randomization Phase Week 48

Change from baseline in Activities of Daily Living Scale from the Friedreich's Ataxia Rating Scale (FARS-ADL) at Randomization Week 48.

Ataxia

Side effects data

From 2021 Phase 2 trial • 350 Patients • NCT03605667

11%

Fall

Weight decreased

Decreased appetite

Diarrhoea

Urinary tract infection

Dizziness

Oedema peripheral

Anxiety

Liver function test increased

Headache

Pulmonary embolism

Fatigue

Facial bones fracture

Lacunar infarction

Atrial fibrillation

Cardiac arrest

Myocardial infarction

Vertigo

Pancreatitis

Small intestinal obstruction

Upper gastrointestinal haemorrhage

Hypothermia

Pelvic mass

Hepatic lesion

Clostridium difficile colitis

Colonic abscess

Diverticulitis

Pneumonia

Sepsis

Frostbite

Hip fracture

Back pain

Breast cancer

Non-small cell lung cancer

Neuropsychiatric symptoms

Aggression

Major depression

Paranoia

Somnambulism

Respiratory failure

Deep vein thrombosis

Thrombosis

100%

80%

60%

40%

20%

Study treatment Arm

Placebo - Randomization Phase/ Troriluzole - OLE Phase

Troriluzole - Randomization Phase

Troriluzole - Randomization Phase/ Troriluzole - OLE Phase

Placebo - Randomization Phase

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Arm 1: BHV-4157Experimental Treatment1 Intervention

Troriluzole 200mg by mouth

Group II: Arm 2: PlaceboPlacebo Group1 Intervention

Placebo 200mg by mouth

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

troriluzole

2018

Completed Phase 2

~350

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Spinocerebellar Ataxias (SCA) often focus on modulating glutamate activity, as excessive glutamate can lead to neurotoxicity and neuronal damage. Troriluzole, for example, is designed to reduce glutamate release and enhance its reuptake, thereby protecting neurons from excitotoxicity. This mechanism is crucial for SCA patients because it aims to slow down the progression of neurodegeneration and alleviate symptoms associated with the disease. By stabilizing glutamate levels, these treatments help maintain neuronal function and potentially improve motor coordination and quality of life for SCA patients.

Glutamate stimulates [3H]phorbol 12,13-dibutyrate binding in cultured Bergmann glia cells.Blockade of pilocarpine-induced cerebellar phosphoinositide hydrolysis with metabotropic glutamate antagonists: evidence for an indirect control of granule cell glutamate release by muscarinic agonists.