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Trial in Adult Subjects With Spinocerebellar Ataxia

Primary Purpose

Spinocerebellar Ataxias, Spinocerebellar Ataxia Genotype Type 1, Spinocerebellar Ataxia Genotype Type 2

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Troriluzole
Placebo
Troriluzole
Sponsored by
Biohaven Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spinocerebellar Ataxias focused on measuring Spinocerebellar Ataxia, SCA

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • St. Joseph's Hospital and Medical Center
  • CNS Trial
  • University of California, Los Angeles
  • University of California, San Francisco
  • University of Colorado Denver
  • University of Florida
  • University of South Florida
  • Emory University
  • Northwestern University
  • University of Chicago
  • Johns Hopkins University
  • Harvard University (Massachusetts General Hospital)
  • Harvard University (Beth Israel Deaconess Medical Center)
  • University of Michigan
  • Columbia University
  • University of Rochester Medical Center
  • University of Texas Southwestern
  • Houston Methodist Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Troriluzole

Placebo

Arm Description

Troriluzole - Randomization Phase: Participants received Troriluzole 140 mg capsules orally once daily (QD) for 8 weeks. Troriluzole/Troriluzole - Extension Phase: Participants received Troriluzole 140 mg capsules orally QD for 48 weeks.

Placebo - Randomization Phase: Participants received matching placebo capsules orally QD for 8 weeks. Placebo/Troriluzole - Extension Phase: Participants who received placebo during randomization phase, received Troriluzole 140 mg capsules orally QD for 48 weeks.

Outcomes

Primary Outcome Measures

Change From Baseline in Total Score on the Scale for the Assessment and Rating of Ataxia (SARA) at Randomization Phase Week 8
The severity of ataxia was assessed with the SARA, an 8-item clinical rating scale from 0 (no ataxia) to 40 (most severe ataxia). The total score was derived as the sum of the individual items, which included gait (0-8), stance (0-6), sitting (0-4), speech disturbance (0-6), finger chase (0-4), nose-finger test (0-4), fast alternating hand movements (0-4), and heel-shin slide (0-4). Since the finger chase, nose-finger test, fast alternating hand movements, and heel-shin slide were repeated on both the right and left side, the average of the right and left side assessments was used to derive the total score. A negative change in score shows improvement.

Secondary Outcome Measures

Number of Participants With Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment-Emergent AEs (TEAEs) During the Randomization Phase
An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition, unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. An SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or suspected transmission of an infectious agent, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. TEAEs were defined as those AEs that developed, worsened, or became serious after the first dose of study drug.
Number of Participants With Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment Emergent AEs (TEAEs) During the Extension Phase
An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition, unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. An SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or suspected transmission of an infectious agent, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. TEAEs were defined as those AEs that developed, worsened, or became serious after the first dose of study drug.
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)
An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition, unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. An SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or suspected transmission of an infectious agent, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. TEAEs were defined as those AEs that developed, worsened, or became serious after the first dose of study drug.
Number of Participants With Impression of Benefit Via Use of the Patient Global Impression of Change (PGI-C) Index Scale During Randomization Phase
PGI-C is a patient self-reported global index scale that was used to rate the response of a condition to therapy. Participants rated their impression of benefit based on the following 7 categories: No change (or condition has gotten worse); Almost the same, hardly any change at all; A little better, but no noticeable change; Somewhat better, but the change has not made any real difference; Moderately better, and a slight but noticeable change; Better and a definitive improvement that has made a real and worthwhile difference; A great deal better and a considerable improvement that has made all the difference.

Full Information

First Posted
November 4, 2016
Last Updated
April 5, 2023
Sponsor
Biohaven Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02960893
Brief Title
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

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 15, 2016 (Actual)
Primary Completion Date
August 18, 2017 (Actual)
Study Completion Date
September 23, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biohaven Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
141 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Troriluzole
Arm Type
Experimental
Arm Description
Troriluzole - Randomization Phase: Participants received Troriluzole 140 mg capsules orally once daily (QD) for 8 weeks. Troriluzole/Troriluzole - Extension Phase: Participants received Troriluzole 140 mg capsules orally QD for 48 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo - Randomization Phase: Participants received matching placebo capsules orally QD for 8 weeks. Placebo/Troriluzole - Extension Phase: Participants who received placebo during randomization phase, received Troriluzole 140 mg capsules orally QD for 48 weeks.
Intervention Type
Drug
Intervention Name(s)
Troriluzole
Intervention Description
Randomization Phase: Neat (i.e., drug substance without excipients); loose filled capsule.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Drug: Placebo Randomization Phase: Matching placebo loose filled capsule.
Intervention Type
Drug
Intervention Name(s)
Troriluzole
Intervention Description
Extension phase: Neat capsule or formulated capsule (i.e., drug substance with excipients).
Primary Outcome Measure Information:
Title
Change From Baseline in Total Score on the Scale for the Assessment and Rating of Ataxia (SARA) at Randomization Phase Week 8
Description
The severity of ataxia was assessed with the SARA, an 8-item clinical rating scale from 0 (no ataxia) to 40 (most severe ataxia). The total score was derived as the sum of the individual items, which included gait (0-8), stance (0-6), sitting (0-4), speech disturbance (0-6), finger chase (0-4), nose-finger test (0-4), fast alternating hand movements (0-4), and heel-shin slide (0-4). Since the finger chase, nose-finger test, fast alternating hand movements, and heel-shin slide were repeated on both the right and left side, the average of the right and left side assessments was used to derive the total score. A negative change in score shows improvement.
Time Frame
Baseline, Randomization Phase Week 8
Secondary Outcome Measure Information:
Title
Number of Participants With Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment-Emergent AEs (TEAEs) During the Randomization Phase
Description
An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition, unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. An SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or suspected transmission of an infectious agent, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. TEAEs were defined as those AEs that developed, worsened, or became serious after the first dose of study drug.
Time Frame
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).
Title
Number of Participants With Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment Emergent AEs (TEAEs) During the Extension Phase
Description
An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition, unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. An SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or suspected transmission of an infectious agent, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. TEAEs were defined as those AEs that developed, worsened, or became serious after the first dose of study drug.
Time Frame
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).
Title
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)
Description
An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition, unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. An SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or suspected transmission of an infectious agent, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. TEAEs were defined as those AEs that developed, worsened, or became serious after the first dose of study drug.
Time Frame
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.
Title
Number of Participants With Impression of Benefit Via Use of the Patient Global Impression of Change (PGI-C) Index Scale During Randomization Phase
Description
PGI-C is a patient self-reported global index scale that was used to rate the response of a condition to therapy. Participants rated their impression of benefit based on the following 7 categories: No change (or condition has gotten worse); Almost the same, hardly any change at all; A little better, but no noticeable change; Somewhat better, but the change has not made any real difference; Moderately better, and a slight but noticeable change; Better and a definitive improvement that has made a real and worthwhile difference; A great deal better and a considerable improvement that has made all the difference.
Time Frame
Randomization Phase Week 8
Other Pre-specified Outcome Measures:
Title
Change From Randomization Baseline in Total Score on the Scale for the Assessment and Rating of Ataxia (SARA) at Extension Phase Week 48
Description
The severity of ataxia was assessed with the SARA, an 8-item clinical rating scale from 0 (no ataxia) to 40 (most severe ataxia). The total score was derived as the sum of the individual items, which included gait (0-8), stance (0-6), sitting (0-4), speech disturbance (0-6), finger chase (0-4), nose-finger test (0-4), fast alternating hand movements (0-4), and heel-shin slide (0-4). Since the finger chase, nose-finger test, fast alternating hand movements, and heel-shin slide were repeated on both the right and left side, the average of the right and left side assessments was used to derive the total score. A negative change in score shows improvement.
Time Frame
Randomization Baseline, Extension Phase Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
St. Joseph's Hospital and Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
CNS Trial
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
University of Colorado Denver
City
Denver
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Harvard University (Massachusetts General Hospital)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Harvard University (Beth Israel Deaconess Medical Center)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
University of Texas Southwestern
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Houston Methodist Research Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34115419
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.
Results Reference
derived

Learn more about this trial

Trial in Adult Subjects With Spinocerebellar Ataxia

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