Troriluzole in Adult Participants With Spinocerebellar Ataxia

NCT03701399 | Active Not Recruiting Phase 3 Results FDA Drug

• 1 other identifier: BHV4157-206
• Study Type: interventional
• Target: 299
• Locations: 2 countries
• Sites: 23

Brief Summary

The purpose of this study is to compare the efficacy of Troriluzole (200 mg once daily) versus placebo after 48 weeks of treatment in subjects with spinocerebellar ataxia (SCA).

Conditions

Spinocerebellar Ataxias; Spinocerebellar Ataxia Type 1; Spinocerebellar Ataxia Type 2; Spinocerebellar Ataxia Type 3; Spinocerebellar Ataxia Type 6; Spinocerebellar Ataxia Type 7; Spinocerebellar Ataxia Type 8; Spinocerebellar Ataxia Type 10

Keywords

Ataxia, SCA, Spinocerebellar Ataxia

Outcome Measures

Primary Outcomes (1)

• Randomization Phase: Change From Baseline in the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) Total Score at Week 48 in SCA Participants

  The f-SARA was a 4-item performance based scale: 1-gait, 2-stance, 3-sitting, 4-speech disturbance (0:normal (no impairment), 1: mildly impaired function, but no assistance required, 2: moderately impaired function, but needs assistance for certain parts of task, 3: severely impaired function to degree that assistance is needed for all parts of the task, 4: unable to perform function). Total score was derived as sum of individual items; ranged from 0 to 16. Higher score indicated worst outcome. A negative change in score showed improvement.

  Randomization Baseline; Week 48

Secondary Outcomes (4)

• Randomization Phase: Change From Baseline in Patient Impression of Function and Activities of Daily Living Scale (PIFAS) Total Score at Week 48 in SCA Participants

  Randomization Baseline, Week 48

• Randomization Phase: Change From Baseline in Friedreich's Ataxia Rating Scale - Activities of Daily Living (FARS-ADL) Total Score at Week 48 in SCA Participants

  Randomization Baseline, Week 48

• Randomization Phase: Change From Baseline in Functional Staging for Ataxia Scale From the Friedreich's Ataxia Rating Scale (FARS-FUNC) Total Score at Week 48 in SCA Participants

  Randomization Baseline, Week 48

• Randomization Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (TESAEs); and AEs Leading to Treatment Discontinuation

  From first dose of study drug to Week 48 plus 30 days (maximum duration: 52 weeks)

Other Outcomes (6)

• Randomization Phase: Change From Baseline in the f-SARA Total Score at Week 48 in SCA3 Participants

  Randomization Baseline; Week 48

• Randomization Phase: Change From Baseline in PIFAS Total Score at Week 48 in SCA3 Participants

  Randomization Baseline, Week 48

• Randomization Phase: Change From Baseline in FARS-ADL Total Score at Week 48 in SCA3 Participants

  Randomization Baseline, Week 48

Study Arms (2)

Troriluzole

EXPERIMENTAL

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.

Drug: troriluzole

Placebo

PLACEBO COMPARATOR

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.

Drug: troriluzole; Drug: Placebo

Interventions

troriluzole DRUG

Administered orally

Placebo; Troriluzole

Placebo DRUG

Administered orally

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with a known or suspected diagnosis of the following specific hereditary ataxias: SCA1, SCA2, SCA3, SCA6, SCA7, SCA8 and SCA10.
• A participant should have a confirmed genotypic diagnosis from a Clinical Laboratory Improvement Amendments (CLIA) certified lab (can produce test results); or,
• A participant has a family member that has a confirmed genotypic diagnosis from a CLIA certified lab (can produce test results) and must be willing to undergo genetic testing to confirm underlying SCA diagnosis; or,
• A participant has a confirmed genotypic diagnosis from a lab that is not CLIA certified and must be willing to undergo genetic testing to confirm underlying SCA diagnosis; or,
• A participant has clinical evidence that supports diagnosis of one of the aforementioned SCA genotypes but does not have producible test results from a CLIA certified lab from either a family member or for his or herself and the participant must be willing to undergo such testing to confirm the SCA diagnosis (in this case, site must wait for results of genotypic testing prior to randomization)
• Ability to ambulate 8 meters without human assistance (canes and other devices allowed)
• Screening Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) total score ≥3.
• Score of ≥1 on gait subsection of the f-SARA
• Determined by the investigator to be medically stable at Baseline/randomization as assessed by medical history, physical examination, laboratory test results, and electrocardiogram testing.

You may not qualify if:

• A ≥ 2-point difference on the Modified Functional SARA score between screening and baseline
• Mini Mental State Exam (MMSE) score \<24
• A prominent spasticity or dystonia that, in the opinion of the investigator, will compromise the ability of the SARA instrument to assess underlying ataxia severity.
• A score of 4 on any individual item (Items 1-4) of the f-SARA
• Participants should be excluded at screening or baseline if medical conditions have arisen or there is a change in disease status that could confound the ability of the SARA to accurately reflect changes in ataxia severity.
• Active liver disease or a history of hepatic intolerance to medications that in the investigator's judgment, is medically significant.

Sponsors & Collaborators

• Biohaven Pharmaceuticals, Inc.: lead

Study Sites (23)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

CNS Trials

Long Beach, California, 90806, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

UCSF

San Francisco, California, 94158, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

University of Florida Health

Gainesville, Florida, 32610, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Emory

Atlanta, Georgia, 30329, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Northwest Neurology, Ltd.

Rolling Meadows, Illinois, 60008, United States

Location

Johns Hopkins Medicine

Lutherville, Maryland, 21093, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Duke University Movement Disorders Clinic

Durham, North Carolina, 27705, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

Swedish Health Services

Seattle, Washington, 98122, United States

Location

Central South University Xiangya Hospital

Changsha, Hunan, 410008, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

Location

Related Publications (3)

• Potashman MH, Popoff E, Powell LC, Beiner MW, Mackenzie A, Coric V, Subramony S, Synofzik M, Schmahmann J, L'Italien G. Measurement Properties of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia. Neurol Ther. 2025 Apr;14(2):527-545. doi: 10.1007/s40120-024-00708-4. Epub 2025 Jan 13.

  PMID: 39806095 DERIVED

• L'Italien GJ, Oikonomou EK, Khera R, Potashman MH, Beiner MW, Maclaine GDH, Schmahmann JD, Perlman S, Coric V. Video-Based Kinematic Analysis of Movement Quality in a Phase 3 Clinical Trial of Troriluzole in Adults with Spinocerebellar Ataxia: A Post Hoc Analysis. Neurol Ther. 2024 Aug;13(4):1287-1301. doi: 10.1007/s40120-024-00625-6. Epub 2024 May 30.

  PMID: 38814532 DERIVED

• Schmahmann JD, Pierce S, MacMore J, L'Italien GJ. Development and Validation of a Patient-Reported Outcome Measure of Ataxia. Mov Disord. 2021 Oct;36(10):2367-2377. doi: 10.1002/mds.28670. Epub 2021 Jun 11.

  PMID: 34115419 DERIVED

MeSH Terms

Conditions

Spinocerebellar Ataxias; Machado-Joseph Disease; Spinocerebellar ataxia 8; Spinocerebellar Ataxia 10; Ataxia; Heart Arrest

Condition Hierarchy (Ancestors)

Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Dyskinesias; Neurologic Manifestations; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Biohaven Pharmaceuticals

clinicaltrials@biohavenpharma.com

203-404-0410

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 5, 2018
• First Posted: October 10, 2018
• Study Start: March 8, 2019
• Primary Completion: February 18, 2022
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 4, 2025
• Results First Posted: February 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2); US (21)