Clinical trial NCT03701399: Troriluzole in Adult Participants With Spinocerebellar Ataxia
Official title: A Phase III, Long-Term, Randomized, Double-blind, Placebo-controlled Trial of Troriluzole in Adult Participants With Spinocerebellar Ataxia.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
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
Lead sponsor: Biohaven Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-10-10
Enrollment: 299
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Randomization Baseline; Week 48
Secondary outcomes:
measure: 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
timeFrame: Randomization Baseline, Week 48
measure: 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
timeFrame: Randomization Baseline, Week 48
measure: 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
timeFrame: Randomization Baseline, Week 48
measure: Randomization Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (TESAEs); and AEs Leading to Treatment Discontinuation
timeFrame: From first dose of study drug to Week 48 plus 30 days (maximum duration: 52 weeks)
Other outcomes:
measure: Randomization Phase: Change From Baseline in the f-SARA Total Score at Week 48 in SCA3 Participants
timeFrame: Randomization Baseline; Week 48
measure: Randomization Phase: Change From Baseline in PIFAS Total Score at Week 48 in SCA3 Participants
timeFrame: Randomization Baseline, Week 48
measure: Randomization Phase: Change From Baseline in FARS-ADL Total Score at Week 48 in SCA3 Participants
timeFrame: Randomization Baseline, Week 48
measure: Randomization Phase: Change From Baseline in FARS-FUNC Total Score at Week 48 in SCA3 Participants
timeFrame: Randomization Baseline, Week 48
measure: Change From Baseline in Clinical Global Impression - Global Improvement Scale (CGI-I) in SCA3 Participants
timeFrame: Randomization Baseline; Week 48
measure: Falls Events in Troriluzole Compared to Placebo for All SCA Participants
timeFrame: Randomization Baseline, Week 48
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Long Beach
country: United States
facility: CNS Trials
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Gainesville
country: United States
facility: University of Florida Health
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Rolling Meadows
country: United States
facility: Northwest Neurology, Ltd.
state: Illinois
city: Lutherville
country: United States
facility: Johns Hopkins Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New York
country: United States
facility: Columbia University
state: New York
city: Durham
country: United States
facility: Duke University Movement Disorders Clinic
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Seattle
country: United States
facility: Swedish Health Services
state: Washington
city: Changsha
country: China
facility: Central South University Xiangya Hospital
state: Hunan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
Study officials:
References:
citation: 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.