Troriluzole in Adult Participants With Spinocerebellar Ataxia

Biohaven

Status and phase: Active, not recruiting; Phase 3

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

Treatments: Drug: troriluzole; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03701399

BHV4157-206

Details and patient eligibility

About

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).

Enrollment: 299 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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299 participants in 2 patient groups, including a placebo group

Troriluzole

Experimental group

Description:

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.

Treatment:

Drug: troriluzole

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: troriluzole