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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Troriluzole | Experimental | 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. |
|
| Placebo | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| troriluzole | Drug | Administered orally |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | The f-SARA was a 4-item performance based scale: 1-gait, 2-stance, 3-sitting, 4-speech disturbance (0:normal (no impairment), 1: mildly impaired function, but no assistance required, 2: moderately impaired function, but needs assistance for certain parts of task, 3: severely impaired function to degree that assistance is needed for all parts of the task, 4: unable to perform function). Total score was derived as sum of individual items; ranged from 0 to 16. Higher score indicated worst outcome. A negative change in score showed improvement. | Randomization Baseline; Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | PIFAS was a 17-item instrument designed to assess the level of functional disability. The scale was rater administered and the items were selected to encompass domains of relevance to SCA (i.e., mobility, speech/swallowing, and fatigue), and to capture function and activities of daily living within these domains. Statements were rated on a 5-point Likert scale ranging from "0" reflecting "not at all" to "4" reflecting "very much." The total score was derived as the sum of the individual items, ranged between 0 to 68. Higher score indicated a worst outcome. A negative change in score showed improvement. |
| Measure | Description | Time Frame |
|---|---|---|
| Randomization Phase: Change From Baseline in the f-SARA Total Score at Week 48 in SCA3 Participants | The f-SARA was a 4-item performance based scale: 1-gait, 2-stance, 3-sitting, 4-speech disturbance (0:normal (no impairment), 1:mildly impaired function, but no assistance required, 2:moderately impaired function, but needs assistance for certain parts of task, 3: severely impaired function to degree that assistance is needed for all parts of the task, 4:unable to perform function). Total score was derived as sum of individual items; ranged from 0 to 16. Higher score indicated worst outcome. A negative change in score shows improvement. |
Inclusion Criteria:
Participants 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 human assistance (canes and other devices allowed)
Screening Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) total score ≥3.
Score of ≥1 on gait subsection of the f-SARA
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:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barrow Neurological Institute | Phoenix | Arizona | 85013 | United States | ||
| CNS Trials |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39806095 | Derived | Potashman MH, Popoff E, Powell LC, Beiner MW, Mackenzie A, Coric V, Subramony S, Synofzik M, Schmahmann J, L'Italien G. Measurement Properties of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia. Neurol Ther. 2025 Apr;14(2):527-545. doi: 10.1007/s40120-024-00708-4. Epub 2025 Jan 13. | |
| 38814532 | Derived |
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A total of 299 participants were enrolled, of which 218 participants were randomized in a 1:1: ratio to receive troriluzole or placebo. Study consisted of double-blind randomization phase (up to Week 48) and open-label extension phase (up to Week 192). The study is ongoing, and results are reported only for randomization phase (up to Week 48).
The study was conducted at 23 sites in 2 countries (21 sites in the US and 2 sites in China).
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Troriluzole | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 5, 2022 | Jan 13, 2025 |
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| Placebo |
| Drug |
Administered orally |
|
| Randomization Baseline, Week 48 |
| 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 | FARS was a scale consisting of combined timed measures of performance, FUNC (0-6, higher score indicated worst outcome), ADL with paramount neurologic examination (0-36, higher score indicated worst outcome), FARSn (0-125, higher score indicated worst outcome). Total score was sum of these 3 subscales: 0-167, higher score indicated worst outcome. For this outcome measure, only FARS-ADL sub-scale was evaluated. It was multicomponent scale designed to assess neurological domains affected in Friedreich's Ataxia, another hereditary cerebellar ataxia disorder. This subscale had been validated in Friedreich's ataxia, was a measure of functional disability, and correlated with SARA total scores. It assessed 9 areas of ADL with response categories rated on 5-point scale with "0" reflecting "normal" and "4" reflecting inability to perform specific function. Total score was derived as sum of individual items, ranging 0-36, higher score indicated worst outcome. FARS-ADL was rater administered. | Randomization Baseline, Week 48 |
| 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 | FARS was a scale consisting of combined timed measures of performance, FUNC (0-6, higher score indicated worst outcome), ADL with paramount neurologic examination (0-36, higher score indicated worst outcome), FARSn (0-125, higher score indicated worst outcome). The total score was a sum of these 3 subscales; 0-167, higher score indicated worst outcome. For this outcome measure, only the FARS-FUNC sub-scale was evaluated. FARS-FUNC was a subscale of the FARS designed to provide functional staging for ataxia in which clinicians were asked to assess function on a 6-stage staging system, with "0" reflecting "normal" and "6" reflecting a stage in participant was "total disabled". | Randomization Baseline, Week 48 |
| Randomization Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (TESAEs); and AEs Leading to Treatment Discontinuation | An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant that did not necessarily had a causal relationship with this treatment. An SAE was defined as any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect in the offspring of the participant or was considered another important medical event. Treatment-emergent AEs (TEAEs) in the randomization phase included any AE with an onset date on or after the first day of double-blind study drug and up to the first day of open-label study drug in the extension phase (for participants entering the extension phase) or last day of the randomization phase study drug + 30 days. | From first dose of study drug to Week 48 plus 30 days (maximum duration: 52 weeks) |
| Randomization Baseline; Week 48 |
| Randomization Phase: Change From Baseline in PIFAS Total Score at Week 48 in SCA3 Participants | PIFAS was a 17-item instrument designed to assess the level of functional disability. The scale is rater administered and the items were selected to encompass domains of relevance to SCA (i.e., mobility, speech/swallowing, and fatigue), and to capture function and activities of daily living within these domains. Statements are rated on a 5-point Likert scale ranging from "0" reflecting "not at all" to "4" reflecting "very much." The total score is derived as the sum of the individual items, ranged between 0 to 68. Higher score indicated a worst outcome. A negative change in score showed improvement. | Randomization Baseline, Week 48 |
| Randomization Phase: Change From Baseline in FARS-ADL Total Score at Week 48 in SCA3 Participants | FARS was a scale consisting of combined timed measures of performance, FUNC (0-6, higher score indicated worst outcome), ADL with paramount neurologic examination (0-36, higher score indicated worst outcome), FARSn (0-125, higher score indicated worst outcome). Total score was sum of these 3 subscales: 0-167, higher score indicated worst outcome. For this outcome measure, only FARS-ADL sub-scale was evaluated. It was multicomponent scale designed to assess neurological domains affected in Friedreich's Ataxia, another hereditary cerebellar ataxia disorder. This subscale had been validated in Friedreich's ataxia, was a measure of functional disability, and correlated with SARA total scores. It assessed 9 areas of ADL with response categories rated on 5-point scale with "0" reflecting "normal" and "4" reflecting inability to perform specific function. Total score was derived as sum of individual items, ranging 0-36, higher score indicated worst outcome. FARS-ADL was rater administered. | Randomization Baseline, Week 48 |
| Randomization Phase: Change From Baseline in FARS-FUNC Total Score at Week 48 in SCA3 Participants | FARS was a scale consisting of combined timed measures of performance, FUNC (0-6, higher score indicated worst outcome), ADL with paramount neurologic examination (0-36, higher score indicated worst outcome), FARSn (0-125, higher score indicated worst outcome). The total score was a sum of these 3 subscales; 0-167, higher score indicated worst outcome. For this outcome measure, only the FARS-FUNC sub-scale was evaluated. FARS-FUNC was a subscale of the FARS designed to provide functional staging for ataxia in which clinicians were asked to assess function on a 6-stage staging system, with "0" reflecting "normal" and "6" reflecting a stage in participant was "total disabled". | Randomization Baseline, Week 48 |
| Change From Baseline in Clinical Global Impression - Global Improvement Scale (CGI-I) in SCA3 Participants | The CGI-I was a 7-point scale that required the clinician to assess how much the participant's illness had improved or worsened relative to the baseline visit and it was rated on a 7 point scale: 1= "Very much improved", 2= "Much improved", 3= "Minimally improved", 4= "No change", 5= "Minimally worse", 6= "Much worse" and 7= "Very much worse". Higher scores indicated greater impairment. | Randomization Baseline; Week 48 |
| Falls Events in Troriluzole Compared to Placebo for All SCA Participants | An AE of Fall was recorded if there was a worsening of frequency of falls or if a fall was associated with an injury. | Randomization Baseline, Week 48 |
| Long Beach |
| California |
| 90806 |
| United States |
| UCLA | Los Angeles | California | 90095 | United States |
| UCSF | San Francisco | California | 94158 | United States |
| University of Colorado Hospital | Aurora | Colorado | 80045 | United States |
| University of Florida Health | Gainesville | Florida | 32610 | United States |
| Mayo Clinic Florida | Jacksonville | Florida | 32224 | United States |
| University of South Florida | Tampa | Florida | 33612 | United States |
| Emory | Atlanta | Georgia | 30329 | United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| University of Chicago | Chicago | Illinois | 60637 | United States |
| Northwest Neurology, Ltd. | Rolling Meadows | Illinois | 60008 | United States |
| Johns Hopkins Medicine | Lutherville | Maryland | 21093 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Columbia University | New York | New York | 10032 | United States |
| Duke University Movement Disorders Clinic | Durham | North Carolina | 27705 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19107 | United States |
| Houston Methodist | Houston | Texas | 77030 | United States |
| Swedish Health Services | Seattle | Washington | 98122 | United States |
| Central South University Xiangya Hospital | Changsha | Hunan | 410008 | China |
| West China Hospital of Sichuan University | Chengdu | Sichuan | 610041 | China |
| L'Italien GJ, Oikonomou EK, Khera R, Potashman MH, Beiner MW, Maclaine GDH, Schmahmann JD, Perlman S, Coric V. Video-Based Kinematic Analysis of Movement Quality in a Phase 3 Clinical Trial of Troriluzole in Adults with Spinocerebellar Ataxia: A Post Hoc Analysis. Neurol Ther. 2024 Aug;13(4):1287-1301. doi: 10.1007/s40120-024-00625-6. Epub 2024 May 30. |
| 34115419 | Derived | 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. |
| FG001 | Placebo | 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. |
| Treated |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Treated analysis set (TAS): The treated analysis set included all randomized/enrolled participants who received at least one dose of study medication (blinded or open label troriluzole, or blinded placebo).
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Troriluzole | 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. |
| BG001 | Placebo | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Number of Participants with Spinocerebellar ataxia (SCA) Genotype | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | The f-SARA was a 4-item performance based scale: 1-gait, 2-stance, 3-sitting, 4-speech disturbance (0:normal (no impairment), 1: mildly impaired function, but no assistance required, 2: moderately impaired function, but needs assistance for certain parts of task, 3: severely impaired function to degree that assistance is needed for all parts of the task, 4: unable to perform function). Total score was derived as sum of individual items; ranged from 0 to 16. Higher score indicated worst outcome. A negative change in score showed improvement. | The modified intent-to-treat (mITT) analysis set in randomization phase included randomized participants who received at least one dose of double-blind study medication (troriluzole or placebo) during the randomization phase and provided a non-missing baseline measurement and at least one non-missing post-baseline efficacy measurement during the randomization phase. Participants with available data were included. Pre-specified randomization strata by SCA genotype. | Posted | Least Squares Mean | Standard Error | score on a scale | Randomization Baseline; Week 48 |
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| Secondary | 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 | PIFAS was a 17-item instrument designed to assess the level of functional disability. The scale was rater administered and the items were selected to encompass domains of relevance to SCA (i.e., mobility, speech/swallowing, and fatigue), and to capture function and activities of daily living within these domains. Statements were rated on a 5-point Likert scale ranging from "0" reflecting "not at all" to "4" reflecting "very much." The total score was derived as the sum of the individual items, ranged between 0 to 68. Higher score indicated a worst outcome. A negative change in score showed improvement. | Participants in mITT analysis set with available data were analyzed. | Posted | Least Squares Mean | Standard Error | score on a scale | Randomization Baseline, Week 48 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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 | FARS was a scale consisting of combined timed measures of performance, FUNC (0-6, higher score indicated worst outcome), ADL with paramount neurologic examination (0-36, higher score indicated worst outcome), FARSn (0-125, higher score indicated worst outcome). Total score was sum of these 3 subscales: 0-167, higher score indicated worst outcome. For this outcome measure, only FARS-ADL sub-scale was evaluated. It was multicomponent scale designed to assess neurological domains affected in Friedreich's Ataxia, another hereditary cerebellar ataxia disorder. This subscale had been validated in Friedreich's ataxia, was a measure of functional disability, and correlated with SARA total scores. It assessed 9 areas of ADL with response categories rated on 5-point scale with "0" reflecting "normal" and "4" reflecting inability to perform specific function. Total score was derived as sum of individual items, ranging 0-36, higher score indicated worst outcome. FARS-ADL was rater administered. | Participants in mITT analysis set with available data were analyzed. | Posted | Least Squares Mean | Standard Error | score on a scale | Randomization Baseline, Week 48 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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 | FARS was a scale consisting of combined timed measures of performance, FUNC (0-6, higher score indicated worst outcome), ADL with paramount neurologic examination (0-36, higher score indicated worst outcome), FARSn (0-125, higher score indicated worst outcome). The total score was a sum of these 3 subscales; 0-167, higher score indicated worst outcome. For this outcome measure, only the FARS-FUNC sub-scale was evaluated. FARS-FUNC was a subscale of the FARS designed to provide functional staging for ataxia in which clinicians were asked to assess function on a 6-stage staging system, with "0" reflecting "normal" and "6" reflecting a stage in participant was "total disabled". | Participants in mITT analysis set with available data were analyzed. | Posted | Least Squares Mean | Standard Error | score on a scale | Randomization Baseline, Week 48 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Randomization Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (TESAEs); and AEs Leading to Treatment Discontinuation | An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant that did not necessarily had a causal relationship with this treatment. An SAE was defined as any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect in the offspring of the participant or was considered another important medical event. Treatment-emergent AEs (TEAEs) in the randomization phase included any AE with an onset date on or after the first day of double-blind study drug and up to the first day of open-label study drug in the extension phase (for participants entering the extension phase) or last day of the randomization phase study drug + 30 days. | The treated analysis set (TAS) included all randomized/enrolled participants who received at least one dose of study medication (blinded or open label troriluzole, or blinded placebo). | Posted | Number | participants | From first dose of study drug to Week 48 plus 30 days (maximum duration: 52 weeks) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Randomization Phase: Change From Baseline in the f-SARA Total Score at Week 48 in SCA3 Participants | The f-SARA was a 4-item performance based scale: 1-gait, 2-stance, 3-sitting, 4-speech disturbance (0:normal (no impairment), 1:mildly impaired function, but no assistance required, 2:moderately impaired function, but needs assistance for certain parts of task, 3: severely impaired function to degree that assistance is needed for all parts of the task, 4:unable to perform function). Total score was derived as sum of individual items; ranged from 0 to 16. Higher score indicated worst outcome. A negative change in score shows improvement. | Participants in mITT analysis set with available data were analyzed. | Posted | Least Squares Mean | Standard Error | score on a scale | Randomization Baseline; Week 48 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Randomization Phase: Change From Baseline in PIFAS Total Score at Week 48 in SCA3 Participants | PIFAS was a 17-item instrument designed to assess the level of functional disability. The scale is rater administered and the items were selected to encompass domains of relevance to SCA (i.e., mobility, speech/swallowing, and fatigue), and to capture function and activities of daily living within these domains. Statements are rated on a 5-point Likert scale ranging from "0" reflecting "not at all" to "4" reflecting "very much." The total score is derived as the sum of the individual items, ranged between 0 to 68. Higher score indicated a worst outcome. A negative change in score showed improvement. | Participants in mITT analysis set with available data were analyzed. | Posted | Least Squares Mean | Standard Error | score on a scale | Randomization Baseline, Week 48 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Randomization Phase: Change From Baseline in FARS-ADL Total Score at Week 48 in SCA3 Participants | FARS was a scale consisting of combined timed measures of performance, FUNC (0-6, higher score indicated worst outcome), ADL with paramount neurologic examination (0-36, higher score indicated worst outcome), FARSn (0-125, higher score indicated worst outcome). Total score was sum of these 3 subscales: 0-167, higher score indicated worst outcome. For this outcome measure, only FARS-ADL sub-scale was evaluated. It was multicomponent scale designed to assess neurological domains affected in Friedreich's Ataxia, another hereditary cerebellar ataxia disorder. This subscale had been validated in Friedreich's ataxia, was a measure of functional disability, and correlated with SARA total scores. It assessed 9 areas of ADL with response categories rated on 5-point scale with "0" reflecting "normal" and "4" reflecting inability to perform specific function. Total score was derived as sum of individual items, ranging 0-36, higher score indicated worst outcome. FARS-ADL was rater administered. | Participants in mITT analysis set with available data were analyzed. | Posted | Least Squares Mean | Standard Error | score on a scale | Randomization Baseline, Week 48 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Randomization Phase: Change From Baseline in FARS-FUNC Total Score at Week 48 in SCA3 Participants | FARS was a scale consisting of combined timed measures of performance, FUNC (0-6, higher score indicated worst outcome), ADL with paramount neurologic examination (0-36, higher score indicated worst outcome), FARSn (0-125, higher score indicated worst outcome). The total score was a sum of these 3 subscales; 0-167, higher score indicated worst outcome. For this outcome measure, only the FARS-FUNC sub-scale was evaluated. FARS-FUNC was a subscale of the FARS designed to provide functional staging for ataxia in which clinicians were asked to assess function on a 6-stage staging system, with "0" reflecting "normal" and "6" reflecting a stage in participant was "total disabled". | Participants in mITT analysis set with available data were analyzed. | Posted | Least Squares Mean | Standard Error | score on a scale | Randomization Baseline, Week 48 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change From Baseline in Clinical Global Impression - Global Improvement Scale (CGI-I) in SCA3 Participants | The CGI-I was a 7-point scale that required the clinician to assess how much the participant's illness had improved or worsened relative to the baseline visit and it was rated on a 7 point scale: 1= "Very much improved", 2= "Much improved", 3= "Minimally improved", 4= "No change", 5= "Minimally worse", 6= "Much worse" and 7= "Very much worse". Higher scores indicated greater impairment. | Participants in mITT analysis set with available data were analyzed. | Posted | Least Squares Mean | Standard Error | score on a scale | Randomization Baseline; Week 48 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Falls Events in Troriluzole Compared to Placebo for All SCA Participants | An AE of Fall was recorded if there was a worsening of frequency of falls or if a fall was associated with an injury. | All randomized participants who received at least one dose of study medication during the randomization phase. | Posted | Number | Number of events | Randomization Baseline, Week 48 |
|
|
For Adverse events (AEs): From first dose of study drug up to Week 48 plus 30 days (maximum duration: 52 weeks) For All-cause mortality: From randomization up to Week 48 plus 30 days (maximum duration: 52 weeks)
For AEs: The treated analysis set (TAS) included all randomized/enrolled participants who received at least one dose of study medication (blinded or open label troriluzole, or blinded placebo)
For All-cause mortality: All randomized participants.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Troriluzole | 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. | 1 | 109 | 6 | 108 | 54 | 108 |
| EG001 | Placebo | 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. | 1 | 109 | 8 | 109 | 58 | 109 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fall | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
| |
| Pulmonary contusion | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
| |
| Human chorionic gonadotropin positive | Investigations | MedDRA 24.0 | Systematic Assessment |
| |
| Liver function test increased | Investigations | MedDRA 24.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Abscess | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Pneumatosis | General disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Haematocoele | Vascular disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Major depression | Psychiatric disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Ureterolithiasis | Renal and urinary disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
| |
| Covid-19 | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Biohaven Pharmaceuticals | 203-404-0410 | clinicaltrials@biohavenpharma.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 27, 2022 | Jan 13, 2025 | SAP_001.pdf |
| ID | Term |
|---|---|
| D020754 | Spinocerebellar Ataxias |
| D017827 | Machado-Joseph Disease |
| C537307 | Spinocerebellar ataxia 8 |
| C566874 | Spinocerebellar Ataxia 10 |
| D001259 | Ataxia |
| D006323 | Heart Arrest |
| ID | Term |
|---|---|
| D002524 | Cerebellar Ataxia |
| D002526 | Cerebellar Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D013132 | Spinocerebellar Degenerations |
| D013118 | Spinal Cord Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| SCA2 |
|
| SCA3 |
|
| SCA6 |
|
| SCA7 |
|
| SCA8 |
|
| SCA10 |
|
| SCA3 |
|
|
|
SCA3 genotype participants |
| Mixed Models Analysis |
| 0.0450 |
| Least square mean difference |
| -0.56 |
| Standard Error of the Mean |
| 0.28 |
| 2-Sided |
| 95 |
| -1.11 |
| -0.01 |
Model based summary statistics were from a mixed model with repeated measures, including fixed effects for treatment, randomization stratum (SCA genotype group), visit, treatment-by-visit interaction, and country. |
| Superiority |
|
|
| OG001 | Placebo | 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. |
|
|
|
|
| OG001 | Placebo | 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. . |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
| Placebo |
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. |
|
|
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
|