Clinical trial NCT02960893: Trial in Adult Subjects With Spinocerebellar Ataxia
Official title: A Phase IIb/III, Randomized, Double-blind, Placebo-controlled Trial of Troriluzole in Adult Subjects With Spinocerebellar Ataxia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Spinocerebellar Ataxias
Spinocerebellar Ataxia Genotype Type 1
Spinocerebellar Ataxia Genotype Type 2
Spinocerebellar Ataxia Genotype Type 3
Spinocerebellar Ataxia Genotype Type 6
Spinocerebellar Ataxia Genotype Type 7
Spinocerebellar Ataxia Genotype Type 8
Spinocerebellar Ataxia Genotype Type 10
Keywords: Spinocerebellar Ataxia
SCA
Lead sponsor: Biohaven Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2016-11-10
Enrollment: 141
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 primary purpose of this study is to compare the efficacy of BHV-4157 (Troriluzole) 140 milligrams (mg) once daily versus placebo after 8 weeks of treatment in subjects with spinocerebellar ataxia (SCA).

Detailed description: The study was conducted in 2 phases: Randomization Phase (8 weeks) followed by an open-label Extension Phase (48 weeks). During the Randomization Phase, participants received either Troriluzole 140 mg or matching placebo up to 8 weeks. Participants who agreed to enter the Extension Phase continued dosing of Troriluzole 140 mg for 48 weeks. The study was subsequently amended to follow participants for a total of 192 weeks in the Extension Phase.

Eligibility criteria: Key Inclusion Criteria:

* Subjects with a known or suspected diagnosis of the following specific hereditary ataxias: SCA1, SCA2, SCA3, SCA6, SCA7, SCA8 and SCA10
* Ability to ambulate 8 meters without assistance (canes and other devices allowed)
* Screening total Scale for the Assessment and Rating of Ataxia (SARA) score ≥8
* Score of ≥ 2 on the gait subsection of the SARA
* Determined by the investigator to be medically stable at baseline/randomization and must be physically able and expected to complete the trial as designed

Key Exclusion Criteria:

* Any medical condition other than one of the hereditary ataxias specified in the inclusion criteria that could predominantly explain or contribute significantly to the subjects' symptoms of ataxia
* Mini Mental State Exam (MMSE) score \< 24
* SARA total score of \> 30 points at screening
* Clinical history of stroke
* Active liver disease or a history of hepatic intolerance to medications that in the investigator's judgment, is medically significant

Primary outcomes:
measure: Change From Baseline in Total Score on the Scale for the Assessment and Rating of Ataxia (SARA) at Randomization Phase Week 8
timeFrame: Baseline, Randomization Phase Week 8
Secondary outcomes:
measure: Number of Participants With Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment-Emergent AEs (TEAEs) During the Randomization Phase
timeFrame: AEs from first dose of study drug to 2 weeks after the last dose (up to 10 weeks). SAEs from signing of informed consent form (ICF) to the start of the Extension (Ext) Phase or 30 days after the last dose (up to 12 weeks).
measure: Number of Participants With Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment Emergent AEs (TEAEs) During the Extension Phase
timeFrame: AEs from first dose Ext Phase troriluzole to 2 weeks after last dose (up to 50 weeks after last subject enrolled in Ext Phase). SAEs from signing of ICF to 30 days after last dose (up to 52 weeks after last subject enrolled in Ext Phase).
measure: Number of Participants Who Received at Least One Dose of Troriluzole in the Randomization Phase or Extension Phase With Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment Emergent AEs (TEAEs)
timeFrame: AEs from first dose of troriluzole to 2 weeks after last dose (up to 50 weeks after last Ext subject enrolled or up to 58 weeks after last Randomization [Rand] subject enrolled). SAEs from signing of ICF to 30 days after the last dose of troriluzole.
measure: Number of Participants With Impression of Benefit Via Use of the Patient Global Impression of Change (PGI-C) Index Scale During Randomization Phase
timeFrame: Randomization Phase Week 8
Other outcomes:
measure: Change From Randomization Baseline in Total Score on the Scale for the Assessment and Rating of Ataxia (SARA) at Extension Phase Week 48
timeFrame: Randomization Baseline, Extension Phase Week 48
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Long Beach
country: United States
facility: CNS Trial
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: University of Colorado Denver
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Harvard University (Massachusetts General Hospital)
state: Massachusetts
city: Boston
country: United States
facility: Harvard University (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: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: Houston Methodist Research Center
state: Texas
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.