What is the mechanism of action of this treatment?

Common treatments for Spinocerebellar Ataxias (SCAs) often target neurotransmitter signaling to alleviate symptoms. BHV-4157, a pro-drug of riluzole, modulates glutamate signaling, which is crucial because excessive glutamate can lead to neurotoxicity and worsen ataxic symptoms. By reducing glutamate release and enhancing its uptake, riluzole helps protect neurons and improve motor coordination. This mechanism is significant for SCA patients as it addresses the underlying neurodegenerative processes, potentially slowing disease progression and improving quality of life.

What side effects are associated with this type of intervention?

Common treatments for Spinocerebellar Ataxias (SCAs) that modulate glutamate signaling, such as riluzole and its pro-drug BHV-4157, often have side effects including dizziness, fatigue, gastrointestinal disturbances (nausea, diarrhea), and elevated liver enzymes. These side effects are generally mild to moderate but can lead to discontinuation in some patients. Other treatments targeting similar pathways may also cause similar adverse effects, emphasizing the need for careful monitoring during therapy.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved treatments for Spinocerebellar Ataxias (SCAs). However, riluzole, which modulates glutamate signaling, is FDA-approved for amyotrophic lateral sclerosis (ALS) and is being studied for its potential benefits in SCAs. BHV-4157, a pro-drug of riluzole, is currently under investigation for its efficacy in treating ataxia, reflecting ongoing efforts to find effective treatments for SCAs by targeting glutamate pathways.

What other types of research exist?

Promising novel alternatives to BHV-4157 for Spinocerebellar Ataxias patients may include antisense oligonucleotide therapies, such as those being developed for other neurodegenerative diseases like ALS. Additionally, drugs targeting AMPA receptors, similar to perampanel used in ALS, could be considered. Further, emerging therapies that modulate glutamate signaling or neuroinflammation may also be promising. Consulting with a healthcare provider for the latest clinical trials and research updates is recommended.

← Back to Search

Pro-Drug

BHV-4157 for Ataxia

Phase 3

Waitlist Available

Research Sponsored by University of California, Los Angeles

Eligibility Criteria Checklist

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

Must have

Age and Sex a. Male and female outpatient subjects between the ages of 18 - 75, inclusive

Non-genetic pure cerebellar and MSA-C subjects will be limited to Inclusion Criteria of Screening SARA score ≥8 or Score of ≥ 2 on gait subsection of the SARA

Must not have

Prior trial of riluzole treatment of at least 8 weeks duration

Use of chlorzoxazone is prohibited 30 days prior to screening and during the study

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 12 months

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial tests BHV-4157, a drug that turns into riluzole in the body, on adults with cerebellar ataxia. The drug helps protect nerve cells and may improve coordination and balance. Riluzole has been shown to prolong survival and slow functional deterioration in patients with ALS.

Who is the study for?

Adults aged 18-75 with cerebellar ataxia, including specific hereditary ataxias or multiple system atrophy-cerebellar type (MSA-C), who can walk 8 meters and are medically stable. Participants must not be pregnant, use two forms of contraception if applicable, have a minimum of six years education, and be able to comply with study requirements.

What is being tested?

The trial is testing BHV-4157 over a period of 12 weeks to treat ataxia. BHV-4157 is related to riluzole, an FDA-approved drug for ALS. The trial includes five visits for examinations, tests, ECGs, questionnaires and there's an optional extension phase lasting another 36 weeks.

What are the potential side effects?

While the side effects specific to BHV-4157 aren't listed here as it's under investigation, similar drugs like riluzole may cause dizziness, gastrointestinal issues such as nausea or diarrhea; liver function changes; weakness; and potential risk for low white blood cell counts.

Eligibility Criteria

Inclusion Criteria

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

Select...

I am between 18 and 75 years old.

Select...

My balance and walking difficulties are moderate to severe.

Select...

I am between 18 and 75 years old.

Select...

I have hereditary ataxia (SCA1, SCA2, SCA3, or SCA6) and have been on Riluzole for over 8 weeks.

Select...

I have a type of ataxia that affects my balance and coordination, not caused by genetics.

Select...

I have been diagnosed with multiple system atrophy of the cerebellar type (MSA-C).

Select...

I can walk 8 meters by myself.

Exclusion Criteria

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

Select...

I have been treated with riluzole for at least 8 weeks.

Select...

I have not taken chlorzoxazone in the last 30 days.

Select...

I haven't taken aminopyridine in the last 30 days.

Select...

My memory and thinking skills test score is below 24.

Select...

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

Select...

I was diagnosed with cancer within the last 5 years.

Select...

I have not had a major depressive episode in the last 6 months.

Select...

I have had neurosyphilis in the past.

Select...

I am currently using approved Alzheimer's treatments.

Select...

I have had a stroke in the past.

Select...

I have had serious stomach or intestine problems.

Select...

I haven't had any major heart, lung, stomach, or liver problems in the last month.

Select...

I have a long-term lung condition.

Select...

My blood pressure is not controlled with medication.

Select...

I couldn't tolerate riluzole treatment.

Select...

My heart condition is in its final stage.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 12 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Scale for the Assessment and Rating of Ataxia

Secondary study objectives

8-Meter Walk Test

Beck Anxiety Inventory

Beck Depression Inventory

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Open ArmExperimental Treatment1 Intervention

All subjects will receive the same dosage throughout the study.

0 / 23Eligibility 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

Common treatments for Spinocerebellar Ataxias (SCAs) often target neurotransmitter signaling to alleviate symptoms. BHV-4157, a pro-drug of riluzole, modulates glutamate signaling, which is crucial because excessive glutamate can lead to neurotoxicity and worsen ataxic symptoms. By reducing glutamate release and enhancing its uptake, riluzole helps protect neurons and improve motor coordination. This mechanism is significant for SCA patients as it addresses the underlying neurodegenerative processes, potentially slowing disease progression and improving quality of life.

4-aminopyridine reverses ataxia and cerebellar firing deficiency in a mouse model of spinocerebellar ataxia type 6.Limiting activity at beta1-subunit-containing GABAA receptor subtypes reduces ataxia.