Troriluzole in Adult Participants With Spinocerebellar Ataxia

Phase 3Active Not RecruitingNCT03701399

Biohaven Pharmaceuticals, Inc.299 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

299

Conditions

Spinocerebellar Ataxias Spinocerebellar Ataxia Type 1 Spinocerebellar Ataxia Type 2 Spinocerebellar Ataxia Type 3 Spinocerebellar Ataxia Type 6 Spinocerebellar Ataxia Type 7

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (23)

Barrow Neurological Institute

Phoenix, Arizona, United States

CNS Trials

Long Beach, California, United States

UCLA

Los Angeles, California, United States

UCSF

San Francisco, California, United States

University of Colorado Hospital

Aurora, Colorado, United States

University of Florida Health

Gainesville, Florida, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

University of South Florida

Tampa, Florida, United States

Emory

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

...and 13 more locations

Outcomes

Primary Outcomes

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.

Time frame: Randomization Baseline; Week 48

Secondary Outcomes

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

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.

Time frame: 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

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.

Time frame: 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

Time frame: 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

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.

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

Troriluzole in Adult Participants With Spinocerebellar Ataxia

Overview

Conditions

Interventions

Eligibility

Locations (23)

Outcomes

Primary Outcomes

Secondary Outcomes