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Trial in Adult Subjects With Spinocerebellar Ataxia

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ClinicalTrials.gov Identifier: NCT02960893
Recruitment Status : Active, not recruiting
First Posted : November 10, 2016
Results First Posted : August 14, 2020
Last Update Posted : April 20, 2021
Sponsor:
Information provided by (Responsible Party):
Biohaven Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
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
Interventions Drug: Troriluzole
Drug: Placebo
Enrollment 141
Recruitment Details 181 participants were screened, and 141 of these participants were randomized to treatment at 18 sites in the United States.
Pre-assignment Details  
Arm/Group Title Troriluzole/Randomization-Troriluzole/Extension Placebo/Randomization-Troriluzole/Extension
Hide Arm/Group Description

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

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

Placebo - Randomization Phase: Participants received matching placebo capsules orally once daily (QD) for 8 weeks.

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

Period Title: Randomization Phase (8-week)
Started 71 70
Completed [1] 64 68
Not Completed 7 2
Reason Not Completed
Adverse Event             5             0
Withdrawal by Subject             2             1
Reason Not Specified             0             1
[1]
Completed the Randomization Phase
Period Title: Extension Phase (48-week)
Started 64 67 [1]
Completed [2] 50 54
Not Completed 14 13
Reason Not Completed
Adverse Event             2             3
Withdrawal by Subject             8             8
Other Reason             2             1
Lost to Follow-up             1             1
Sponsors Decision             1             0
[1]
One participant in placebo arm who completed Randomization Phase did not continue to Extension Phase
[2]
Completed the 48-week Extension Phase
Arm/Group Title Troriluzole - Randomization Phase Placebo - Randomization Phase Total
Hide Arm/Group Description Participants received Troriluzole 140 milligram (mg) capsules orally once daily (QD) for 8 weeks. Participants received matching placebo capsules orally QD for 8 weeks. Total of all reporting groups
Overall Number of Baseline Participants 71 70 141
Hide Baseline Analysis Population Description
Safety Analysis Set (Randomization Phase): All participants who received at least one dose of study drug during the Randomization Phase.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 71 participants 70 participants 141 participants
52.5  (15.08) 51.6  (13.74) 52.1  (14.39)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 70 participants 141 participants
Female
35
  49.3%
37
  52.9%
72
  51.1%
Male
36
  50.7%
33
  47.1%
69
  48.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 70 participants 141 participants
Hispanic or Latino
6
   8.5%
6
   8.6%
12
   8.5%
Not Hispanic or Latino
65
  91.5%
64
  91.4%
129
  91.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 70 participants 141 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
5
   7.0%
11
  15.7%
16
  11.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
   8.5%
4
   5.7%
10
   7.1%
White
56
  78.9%
53
  75.7%
109
  77.3%
More than one race
1
   1.4%
0
   0.0%
1
   0.7%
Unknown or Not Reported
3
   4.2%
2
   2.9%
5
   3.5%
Spinocerebellar Ataxia (SCA) Genotype   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 70 participants 141 participants
SCA1
17
  23.9%
18
  25.7%
35
  24.8%
SCA2
19
  26.8%
18
  25.7%
37
  26.2%
SCA3
8
  11.3%
6
   8.6%
14
   9.9%
SCA6
16
  22.5%
15
  21.4%
31
  22.0%
SCA7
2
   2.8%
5
   7.1%
7
   5.0%
SCA8
6
   8.5%
6
   8.6%
12
   8.5%
SCA10
3
   4.2%
2
   2.9%
5
   3.5%
[1]
Measure Description: The Spinocerebellar Ataxia (SCA) data displayed are not grades or stages of disease, but rather the SCA genotypes, which do not correlate with severity of disease.
1.Primary Outcome
Title Change From Baseline in Total Score on the Scale for the Assessment and Rating of Ataxia (SARA) at Randomization Phase Week 8
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): All randomized participants with at least one dose of study drug and a baseline and post-baseline Total SARA score during the Randomization Phase. Here, number of participants analyzed signifies the number of evaluable participants with change from baseline in Total SARA score at Week 8.
Arm/Group Title Troriluzole - Randomization Phase Placebo - Randomization Phase
Hide Arm/Group Description:
Participants received Troriluzole 140 milligram (mg) capsules orally (QD) for 8 weeks.
Participants received matching placebo capsules orally QD for 8 weeks.
Overall Number of Participants Analyzed 63 68
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.810  (1.7653) -1.059  (2.3221)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Troriluzole - Randomization Phase, Placebo - Randomization Phase
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.519
Comments Significance was evaluated at a 2-sided alpha level of 0.05
Method Mixed Model with Repeated Measures
Comments Fixed effects: treatment, baseline (BL) gait severity, visit, treatment-by-visit interaction; Covariate: BL Total SARA score; Random effect: subject
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.5 to 0.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.4
Estimation Comments [Not Specified]
2.Secondary Outcome
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
Hide 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).
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (Randomization Phase): All participants who received at least one dose of study drug during the Randomization Phase.
Arm/Group Title Troriluzole - Randomization Phase Placebo - Randomization Phase
Hide Arm/Group Description:
Participants received Troriluzole 140 milligram (mg) capsules orally (QD) for 8 weeks.
Participants received matching placebo capsules orally QD for 8 weeks.
Overall Number of Participants Analyzed 71 70
Measure Type: Count of Participants
Unit of Measure: Participants
Deaths
0
   0.0%
0
   0.0%
SAEs
4
   5.6%
1
   1.4%
Discontinued due to AEs
3
   4.2%
0
   0.0%
TEAEs
40
  56.3%
35
  50.0%
3.Secondary Outcome
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
Hide 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).
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (Extension Phase): All participants who received at least one dose of study drug during the Extension Phase.
Arm/Group Title Troriluzole/Troriluzole - Extension Phase Placebo/Troriluzole - Extension Phase
Hide Arm/Group Description:
Participants received Troriluzole 140 mg capsules orally QD for 48 weeks.
Participants received Troriluzole 140 mg capsules orally QD for 48 weeks.
Overall Number of Participants Analyzed 64 67
Measure Type: Count of Participants
Unit of Measure: Participants
Deaths
0
   0.0%
0
   0.0%
SAEs
2
   3.1%
2
   3.0%
Discontinued due to AEs
3
   4.7%
4
   6.0%
TEAEs
50
  78.1%
56
  83.6%
4.Secondary Outcome
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)
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of Troriluzole during the Randomization Phase or Extension Phase.
Arm/Group Title Troriluzole - Overall
Hide Arm/Group Description:
Participants received at least one dose of Troriluzole 140 mg capsule orally QD during the Randomization Phase or Extension Phase.
Overall Number of Participants Analyzed 138
Measure Type: Count of Participants
Unit of Measure: Participants
Deaths
0
   0.0%
SAEs
8
   5.8%
Discontinued due to AEs
11
   8.0%
TEAEs
117
  84.8%
5.Secondary Outcome
Title Number of Participants With Impression of Benefit Via Use of the Patient Global Impression of Change (PGI-C) Index Scale During Randomization Phase
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): All randomized participants with at least one dose of study drug and a baseline and post-baseline Total SARA score during the Randomization Phase. Here, number of participants analyzed signifies the number of evaluable participants for PGI-C index at Week 8.
Arm/Group Title Troriluzole - Randomization Phase Placebo - Randomization Phase
Hide Arm/Group Description:
Participants received Troriluzole 140 milligram (mg) capsules orally once daily (QD) for 8 weeks.
Participants received matching placebo capsules orally QD for 8 weeks.
Overall Number of Participants Analyzed 63 66
Measure Type: Count of Participants
Unit of Measure: Participants
No Change
31
  49.2%
27
  40.9%
Almost the same
15
  23.8%
15
  22.7%
A little better
7
  11.1%
11
  16.7%
Somewhat better
3
   4.8%
2
   3.0%
Moderately better
3
   4.8%
7
  10.6%
Better
4
   6.3%
4
   6.1%
A great deal better
0
   0.0%
0
   0.0%
6.Other Pre-specified Outcome
Title Change From Randomization Baseline in Total Score on the Scale for the Assessment and Rating of Ataxia (SARA) at Extension Phase Week 48
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): All randomized participants with at least one dose of study drug and a baseline and post-baseline Total SARA score during the Randomization Phase. Here, number of participants analyzed signifies the number of evaluable participants with change from Randomization baseline in Total SARA score at Week 48.
Arm/Group Title Troriluzole - Extension Phase
Hide Arm/Group Description:
Participants received Troriluzole 140 mg capsules orally QD for 48 weeks.
Overall Number of Participants Analyzed 96
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.42  (2.522)
Time Frame AEs from first dose of study drug to 2 weeks after last dose (Rand Phase up to 10 weeks; Ext Phase up to 50 weeks after last Ext subject enrolled). SAEs from ICF to 30 days after last dose of study drug (up to 52 weeks after last Ext subject enrolled).
Adverse Event Reporting Description

Safety Analysis Set (Randomization Phase): All participants who received at least one dose of study drug during the Randomization Phase

Safety Analysis Set (Extension Phase): All participants who received at least one dose of study drug during the Extension Phase

 
Arm/Group Title Troriluzole - Randomization Phase Placebo - Randomization Phase Troriluzole/Troriluzole - Extension Phase Placebo/Troriluzole - Extension Phase
Hide Arm/Group Description Participants received Troriluzole 140 milligram (mg) capsules orally once daily (QD) for 8 weeks. Participants received matching placebo capsules orally QD for 8 weeks. Participants received Troriluzole 140 mg capsules orally QD for 48 weeks. Participants received Troriluzole 140 mg capsules orally QD for 48 weeks.
All-Cause Mortality
Troriluzole - Randomization Phase Placebo - Randomization Phase Troriluzole/Troriluzole - Extension Phase Placebo/Troriluzole - Extension Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/71 (0.00%)   0/70 (0.00%)   0/64 (0.00%)   0/67 (0.00%) 
Hide Serious Adverse Events
Troriluzole - Randomization Phase Placebo - Randomization Phase Troriluzole/Troriluzole - Extension Phase Placebo/Troriluzole - Extension Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/71 (5.63%)   1/70 (1.43%)   2/64 (3.13%)   2/67 (2.99%) 
Cardiac disorders         
Atrial fibrillation  1  1/71 (1.41%)  0/70 (0.00%)  0/64 (0.00%)  0/67 (0.00%) 
General disorders         
Asthenia  1  1/71 (1.41%)  0/70 (0.00%)  0/64 (0.00%)  0/67 (0.00%) 
Inflammation  1  0/71 (0.00%)  0/70 (0.00%)  1/64 (1.56%)  0/67 (0.00%) 
Pyrexia  1  0/71 (0.00%)  0/70 (0.00%)  1/64 (1.56%)  0/67 (0.00%) 
Chest discomfort  1  0/71 (0.00%)  1/70 (1.43%)  0/64 (0.00%)  0/67 (0.00%) 
Infections and infestations         
Pneumonia  1  0/71 (0.00%)  0/70 (0.00%)  1/64 (1.56%)  2/67 (2.99%) 
Investigations         
Blood creatine phosphokinase increased  1  1/71 (1.41%)  0/70 (0.00%)  0/64 (0.00%)  0/67 (0.00%) 
Metabolism and nutrition disorders         
Dehydration  1  1/71 (1.41%)  0/70 (0.00%)  0/64 (0.00%)  0/67 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  1/71 (1.41%)  0/70 (0.00%)  0/64 (0.00%)  0/67 (0.00%) 
Nervous system disorders         
Cerebral infarction  1  1/71 (1.41%)  0/70 (0.00%)  0/64 (0.00%)  0/67 (0.00%) 
Syncope  1  0/71 (0.00%)  0/70 (0.00%)  1/64 (1.56%)  0/67 (0.00%) 
Psychiatric disorders         
Suicidal ideation  1  1/71 (1.41%)  0/70 (0.00%)  0/64 (0.00%)  0/67 (0.00%) 
Surgical and medical procedures         
Hospitalisation  1  1/71 (1.41%)  0/70 (0.00%)  0/64 (0.00%)  0/67 (0.00%) 
Vascular disorders         
Hypertension  1  0/71 (0.00%)  1/70 (1.43%)  0/64 (0.00%)  0/67 (0.00%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Troriluzole - Randomization Phase Placebo - Randomization Phase Troriluzole/Troriluzole - Extension Phase Placebo/Troriluzole - Extension Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   22/71 (30.99%)   18/70 (25.71%)   28/64 (43.75%)   37/67 (55.22%) 
Gastrointestinal disorders         
Nausea  1  4/71 (5.63%)  4/70 (5.71%)  4/64 (6.25%)  6/67 (8.96%) 
General disorders         
Fatigue  1  6/71 (8.45%)  3/70 (4.29%)  1/64 (1.56%)  7/67 (10.45%) 
Infections and infestations         
Viral upper respiratory tract infection  1  0/71 (0.00%)  1/70 (1.43%)  5/64 (7.81%)  5/67 (7.46%) 
Upper respiratory tract infection  1  0/71 (0.00%)  1/70 (1.43%)  2/64 (3.13%)  4/67 (5.97%) 
Urinary tract infection  1  0/71 (0.00%)  3/70 (4.29%)  0/64 (0.00%)  6/67 (8.96%) 
Injury, poisoning and procedural complications         
Fall  1  6/71 (8.45%)  2/70 (2.86%)  11/64 (17.19%)  8/67 (11.94%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  2/71 (2.82%)  0/70 (0.00%)  3/64 (4.69%)  4/67 (5.97%) 
Back pain  1  2/71 (2.82%)  3/70 (4.29%)  3/64 (4.69%)  4/67 (5.97%) 
Muscle spasms  1  4/71 (5.63%)  2/70 (2.86%)  2/64 (3.13%)  3/67 (4.48%) 
Nervous system disorders         
Dizziness  1  8/71 (11.27%)  1/70 (1.43%)  4/64 (6.25%)  5/67 (7.46%) 
Headache  1  4/71 (5.63%)  4/70 (5.71%)  3/64 (4.69%)  6/67 (8.96%) 
Balance disorder  1  1/71 (1.41%)  0/70 (0.00%)  4/64 (6.25%)  6/67 (8.96%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Biohaven Pharmaceuticals
Phone: 203-404-0410
EMail: clinicaltrials@biohavenpharma.com
Layout table for additonal information
Responsible Party: Biohaven Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02960893    
Other Study ID Numbers: BHV4157-201
First Submitted: November 4, 2016
First Posted: November 10, 2016
Results First Submitted: July 24, 2020
Results First Posted: August 14, 2020
Last Update Posted: April 20, 2021