- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT03701399
Trorilutsoli aikuisilla potilailla, joilla on spinocerebellaarinen ataksia
Vaihe III, pitkäaikainen, satunnaistettu, kaksoissokkoutettu, lumekontrolloitu koe trorilutsolilla aikuisilla potilailla, joilla on spinocerebellaarinen ataksia.
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).
Tutkimuksen yleiskatsaus
Tila
Ehdot
Interventio / Hoito
Opintotyyppi
Ilmoittautuminen (Todellinen)
Vaihe
- Vaihe 3
Laajennettu käyttöoikeus
Yhteystiedot ja paikat
Opiskelupaikat
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Hunan
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Changsha, Hunan, Kiina, 410008
- Central South University Xiangya Hospital
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Sichuan
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Chengdu, Sichuan, Kiina, 610041
- West China Hospital of Sichuan University
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-
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Arizona
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Phoenix, Arizona, Yhdysvallat, 85013
- Barrow Neurological Institute
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California
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Long Beach, California, Yhdysvallat, 90806
- CNS Trials
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Los Angeles, California, Yhdysvallat, 90095
- UCLA
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San Francisco, California, Yhdysvallat, 94158
- UCSF
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Colorado
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Aurora, Colorado, Yhdysvallat, 80045
- University of Colorado Hospital
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Florida
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Gainesville, Florida, Yhdysvallat, 32610
- University of Florida Health
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Jacksonville, Florida, Yhdysvallat, 32224
- Mayo Clinic Florida
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Tampa, Florida, Yhdysvallat, 33612
- University of South Florida
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Georgia
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Atlanta, Georgia, Yhdysvallat, 30329
- Emory
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Illinois
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Chicago, Illinois, Yhdysvallat, 60611
- Northwestern University
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Chicago, Illinois, Yhdysvallat, 60637
- University of Chicago
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Rolling Meadows, Illinois, Yhdysvallat, 60008
- Northwest Neurology, Ltd.
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Maryland
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Lutherville, Maryland, Yhdysvallat, 21093
- Johns Hopkins Medicine
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Massachusetts
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Boston, Massachusetts, Yhdysvallat, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Yhdysvallat, 02114
- Massachusetts General Hospital
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Michigan
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Ann Arbor, Michigan, Yhdysvallat, 48109
- University of Michigan
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New York
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New York, New York, Yhdysvallat, 10032
- Columbia University
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North Carolina
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Durham, North Carolina, Yhdysvallat, 27705
- Duke University Movement Disorders Clinic
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Pennsylvania
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Philadelphia, Pennsylvania, Yhdysvallat, 19107
- University of Pennsylvania
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Texas
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Houston, Texas, Yhdysvallat, 77030
- Houston Methodist
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Washington
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Seattle, Washington, Yhdysvallat, 98122
- Swedish Health Services
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
Inclusion Criteria:
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Participants with a known or suspected diagnosis of the following specific hereditary ataxias: SCA1, SCA2, SCA3, SCA6, SCA7, SCA8 and SCA10.
- A participant should have a confirmed genotypic diagnosis from a Clinical Laboratory Improvement Amendments (CLIA) certified lab (can produce test results); or,
- 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,
- 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,
- 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)
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Ability to ambulate 8 meters without human assistance (canes and other devices allowed)
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Screening Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) total score ≥3.
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Score of ≥1 on gait subsection of the f-SARA
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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:
- A ≥ 2-point difference on the Modified Functional SARA score between screening and baseline
- Mini Mental State Exam (MMSE) score <24
- 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.
- 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.
- A score of 4 on any individual item (Items 1-4) of the f-SARA
- 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.
- Active liver disease or a history of hepatic intolerance to medications that in the investigator's judgment, is medically significant.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Nelinkertaistaa
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
|
Kokeellinen: 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. |
Administered orally |
|
Placebo Comparator: 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. |
Administered orally Administered orally |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
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
Aikaikkuna: Randomization Baseline; Week 48
|
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
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
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
Aikaikkuna: Randomization Baseline, Week 48
|
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. |
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
Aikaikkuna: Randomization Baseline, Week 48
|
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
Aikaikkuna: Randomization Baseline, Week 48
|
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
Aikaikkuna: From first dose of study drug to Week 48 plus 30 days (maximum duration: 52 weeks)
|
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)
|
Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Randomization Phase: Change From Baseline in the f-SARA Total Score at Week 48 in SCA3 Participants
Aikaikkuna: Randomization Baseline; Week 48
|
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. |
Randomization Baseline; Week 48
|
|
Randomization Phase: Change From Baseline in PIFAS Total Score at Week 48 in SCA3 Participants
Aikaikkuna: Randomization Baseline, Week 48
|
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
Aikaikkuna: Randomization Baseline, Week 48
|
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
Aikaikkuna: Randomization Baseline, Week 48
|
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
Aikaikkuna: Randomization Baseline; Week 48
|
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
Aikaikkuna: Randomization Baseline, Week 48
|
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
|
Yhteistyökumppanit ja tutkijat
Sponsori
Julkaisuja ja hyödyllisiä linkkejä
Yleiset julkaisut
- 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.
- 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.
- 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.
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Todellinen)
Opintojen valmistuminen (Todellinen)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Neurologiset ilmenemismuodot
- Aivojen sairaudet
- Keskushermoston sairaudet
- Hermoston sairaudet
- Sydän-ja verisuonitaudit
- Sydänsairaudet
- Geneettiset sairaudet, synnynnäiset
- Neurodegeneratiiviset sairaudet
- Heredodegeneratiiviset häiriöt, hermosto
- Selkäydinsairaudet
- Dyskinesiat
- Pikkuaivojen sairaudet
- Pikkuaivojen ataksia
- Spinocerebellaariset rappeumat
- Synnynnäiset, perinnölliset ja vastasyntyneiden sairaudet ja poikkeavuudet
- Patologiset tilat, merkit ja oireet
- Merkit ja oireet
- Sydänpysähdys
- Ataksia
- Spinocerebellar ataksia
- Machado-Josephin tauti
- Spinocerebellaarinen ataksia 8
- Spinocerebellaarinen ataksia 10
Muut tutkimustunnusnumerot
- BHV4157-206
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
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