Troriluzole in Adult Participants With Spinocerebellar Ataxia

Phase 3

Active, not recruiting

• Conditions: Spinocerebellar Ataxia Type 1; Spinocerebellar Ataxia Type 2; Spinocerebellar Ataxia Type 3; Spinocerebellar Ataxia Type 6; Spinocerebellar Ataxia Type 7; Spinocerebellar Ataxia Type 10; Spinocerebellar Ataxias; Spinocerebellar Ataxia Type 8
• Interventions: Drug: troriluzole; Drug: Placebo

• Registration Number: NCT03701399
• Lead Sponsor: Biohaven Pharmaceuticals, Inc.

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-10-05
• Study First Submitted QC: 2018-10-08
• Study First Posted: 2018-10-10
• Study Start: 2019-03-08
• Primary Completion: 2022-02-18
• Disposition First Submitted: 2023-01-18
• Disposition First Submitted QC: 2023-01-19
• Disposition First Posted: 2023-01-20
• Status Verified: 2025-01
• Results First Submitted: 2025-01-16
• Results First Submitted QC: 2025-01-16
• Last Update Submitted: 2025-01-16
• Results First Posted: 2025-02-10
• Last Update Posted: 2025-02-10
• Study Completion: 2025-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 299

Inclusion Criteria

1. Participants with a known or suspected diagnosis of the following specific hereditary ataxias: SCA1, SCA2, SCA3, SCA6, SCA7, SCA8 and SCA10.

   1. A participant should have a confirmed genotypic diagnosis from a Clinical Laboratory Improvement Amendments (CLIA) certified lab (can produce test results); or,
   2. 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,
   3. 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,
   4. 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)

2. Ability to ambulate 8 meters without human assistance (canes and other devices allowed)

3. Screening Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) total score ≥3.

4. Score of ≥1 on gait subsection of the f-SARA

5. Determined by the investigator to be medically stable at Baseline/randomization as assessed by medical history, physical examination, laboratory test results, and electrocardiogram testing.

Exclusion Criteria

1. A ≥ 2-point difference on the Modified Functional SARA score between screening and baseline
2. Mini Mental State Exam (MMSE) score <24
3. Any medical condition other than one of the hereditary ataxias specified in the inclusion criteria that could predominantly explain or contribute significantly to the participants' symptoms of ataxia.
4. 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.
5. A score of 4 on any individual item (Items 1-4) of the f-SARA
6. 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.
7. Active liver disease or a history of hepatic intolerance to medications that in the investigator's judgment, is medically significant.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Troriluzole	troriluzole	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.
Placebo	troriluzole	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.
Placebo	Placebo	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.

Primary Outcome Measures

Name	Time	Method
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	Randomization Baseline; Week 48	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.

Secondary Outcome Measures

Name	Time	Method
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	PIFAS was a 17-item instrument designed to assess the level of functional disability. The scale was rater administered and the items were selected to encompass domains of relevance to SCA (i.e., mobility, speech/swallowing, and fatigue), and to capture function and activities of daily living within these domains. Statements were rated on a 5-point Likert scale ranging from "0" reflecting "not at all" to "4" reflecting "very much." The total score was derived as the sum of the individual items, ranged between 0 to 68. Higher score indicated a worst outcome. A negative change in score showed improvement.
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	FARS was a scale consisting of combined timed measures of performance, FUNC (0-6, higher score indicated worst outcome), ADL with paramount neurologic examination (0-36, higher score indicated worst outcome), FARSn (0-125, higher score indicated worst outcome). The total score was a sum of these 3 subscales; 0-167, higher score indicated worst outcome.; For this outcome measure, only the FARS-FUNC sub-scale was evaluated. FARS-FUNC was a subscale of the FARS designed to provide functional staging for ataxia in which clinicians were asked to assess function on a 6-stage staging system, with "0" reflecting "normal" and "6" reflecting a stage in participant was "total disabled".
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	FARS was a scale consisting of combined timed measures of performance, FUNC (0-6, higher score indicated worst outcome), ADL with paramount neurologic examination (0-36, higher score indicated worst outcome), FARSn (0-125, higher score indicated worst outcome). Total score was sum of these 3 subscales: 0-167, higher score indicated worst outcome. For this outcome measure, only FARS-ADL sub-scale was evaluated. It was multicomponent scale designed to assess neurological domains affected in Friedreich's Ataxia, another hereditary cerebellar ataxia disorder. This subscale had been validated in Friedreich's ataxia, was a measure of functional disability, and correlated with SARA total scores. It assessed 9 areas of ADL with response categories rated on 5-point scale with "0" reflecting "normal" and "4" reflecting inability to perform specific function. Total score was derived as sum of individual items, ranging 0-36, higher score indicated worst outcome. FARS-ADL was rater administered.
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)	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant that did not necessarily had a causal relationship with this treatment. An SAE was defined as any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect in the offspring of the participant or was considered another important medical event. Treatment-emergent AEs (TEAEs) in the randomization phase included any AE with an onset date on or after the first day of double-blind study drug and up to the first day of open-label study drug in the extension phase (for participants entering the extension phase) or last day of the randomization phase study drug + 30 days.

Trial Locations

Locations (23)

University of South Florida; 🇺🇸 Tampa, Florida, United States

UCLA; 🇺🇸 Los Angeles, California, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Swedish Health Services; 🇺🇸 Seattle, Washington, United States

Johns Hopkins Medicine; 🇺🇸 Lutherville, Maryland, United States

University of Florida Health; 🇺🇸 Gainesville, Florida, United States

CNS Trials; 🇺🇸 Long Beach, California, United States

Barrow Neurological Institute; 🇺🇸 Phoenix, Arizona, United States

UCSF; 🇺🇸 San Francisco, California, United States

Duke University Movement Disorders Clinic; 🇺🇸 Durham, North Carolina, United States

Central South University Xiangya Hospital; 🇨🇳 Changsha, Hunan, China

West China Hospital of Sichuan University; 🇨🇳 Chengdu, Sichuan, China

University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States

Emory; 🇺🇸 Atlanta, Georgia, United States

Mayo Clinic Florida; 🇺🇸 Jacksonville, Florida, United States

Northwest Neurology, Ltd.; 🇺🇸 Rolling Meadows, Illinois, United States

Columbia University; 🇺🇸 New York, New York, United States

Houston Methodist; 🇺🇸 Houston, Texas, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States