Safety and Tolerability Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS) (CL201)
16. června 2021 aktualizováno: Knopp Biosciences
A 2-Part, Randomized, Double-Blind, Safety and Tolerability Study Evaluating KNS-760704 in Patients With Amyotrophic Lateral Sclerosis (ALS)
This was a 2-part study of dexpramipexole in patients with ALS.
Part 1 was a randomized, placebo-controlled, multi-center study to evaluate the safety, tolerability, and clinical effects of oral administration of 3 dosage levels of dexpramipexole vs. placebo for 12 weeks.
Part 2 was a randomized, double-blind, 2-arm, parallel group, extension study evaluating the safety, tolerability, and clinical effects of oral administration of 2 dosage levels of dexpramipexole for up to 72 weeks.
Přehled studie
Postavení
Dokončeno
Podmínky
Detailní popis
This study was a two-part, multicenter, double-blind study in subjects with ALS to evaluate the safety and tolerability of dexpramipexole treatment, as well as the preliminary effects on measures of clinical function and mortality of dexpramipexole treatment.
In part 1, 102 subjects with ALS were randomized at 20 US sites to receive placebo, dexpramipexole at 50 mg/day; dexpramipexole at 150 mg/day; or dexpramipexole at 300 mg/day for 12 weeks. Participants who completed Part 1 were eligible to enroll into Part 2.
Part 2 was a randomized, double-blind, 2-arm, parallel-group, extension study evaluating the longer-term safety, tolerability, and clinical effects of oral administration of 2 dosage levels of dexpramipexole. In part 2, following a 4-week, placebo washout, continuing subjects received dexpramipexole at 50 mg/day or 300 mg/day as double-blind treatment for up to 72 additional weeks (Part 2 duration was up to a total of 76 weeks, including the 4 week placebo portion).
Typ studie
Intervenční
Zápis (Aktuální)
194
Fáze
- Fáze 2
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Arkansas
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Little Rock, Arkansas, Spojené státy, 72205
- University of Arkansas for Medical Sciences
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California
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Los Angeles, California, Spojené státy, 90095
- UCLA, Dept. of Neurology - Neuromuscular/ALS Research Center
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San Francisco, California, Spojené státy, 94115
- The Forbes Norris MDA/ALS Research Center
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Colorado
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Aurora, Colorado, Spojené státy, 80045
- University of Colorado Health Sciences Center
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Florida
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Miami, Florida, Spojené státy, 33136
- University of Miami Miller School of Medicine
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Kansas
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Kansas City, Kansas, Spojené státy, 66160
- University of Kansas Medical Center
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Maryland
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Baltimore, Maryland, Spojené státy, 21228
- Johns Hopkins University School of Medicine
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Massachusetts
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Boston, Massachusetts, Spojené státy, 02129
- Massachusettes General Hospital
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Missouri
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Saint Louis, Missouri, Spojené státy, 63110
- Washington University School of Medicine
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Nebraska
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Lincoln, Nebraska, Spojené státy, 68506
- Bryan LGH Medical Center East
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New York
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New York, New York, Spojené státy, 10032
- Columbia University, Lou Gehrig MDA/ALS Research Center
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Syracuse, New York, Spojené státy, 13210
- SUNY Upstate Medical University
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Oregon
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Portland, Oregon, Spojené státy, 97239
- Oregon Health Sciences University
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Pennsylvania
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Hershey, Pennsylvania, Spojené státy, 17033
- Penn State Hershey Medical Center
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Philadelphia, Pennsylvania, Spojené státy, 19102
- Drexel University College of Medicine
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Pittsburgh, Pennsylvania, Spojené státy, 15213
- University of Pittsburgh School of Medicine
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Tennessee
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Nashville, Tennessee, Spojené státy, 37232
- Vanderbilt University Medical Center
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Texas
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San Antonio, Texas, Spojené státy, 78229
- University of Texas Health Sciences Center of San Antonio
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Utah
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Salt Lake City, Utah, Spojené státy, 84132
- University of Utah
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Virginia
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Charlottesville, Virginia, Spojené státy, 22908
- University of Virginia Health System
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Washington
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Seattle, Washington, Spojené státy, 98195
- University of Washington
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
21 let až 80 let (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
Inclusion Criteria:
- Patients with diagnosis of familial or sporadic ALS, defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology El Escorial criteria
- Patients with ALS symptom onset < 24 months from randomization
- Patients with upright vital capacity (VC) > 65% of predicted for age, height, and gender
Exclusion Criteria:
- Patients in whom causes of neuromuscular weakness other than ALS have not been excluded
- Patients without clinical evidence of upper motor neuron dysfunction
- Patients with clinically suspected ALS according to the World Federation of Neurology El Escorial criteria
- Patients with prior exposure to KNS-760704 or the R(+) enantiomer of pramipexole (i.e., R(+)-pramipexole)
- Patients taking other investigational agents (including lithium) within 30 days of randomization or during the study
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Komparátor placeba: Part 1: Placebo or Dexpramipexole
During Part 1, subjects received twice daily doses of dexpramipexole (50 mg/day, 150 mg/day, or 300 mg/day) or matching placebo for approximately 12 weeks.
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Placebo: 2 tablets taken orally twice daily
Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
Ostatní jména:
Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily
Ostatní jména:
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Ostatní jména:
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Experimentální: Part 2: Placebo washout
At the beginning of Part 2, subjects received twice daily doses of placebo for approximately 4 weeks.
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Placebo: 2 tablets taken orally twice daily
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Experimentální: Part 2: Dexpramipexole
Following the Part 2 placebo washout, subjects received dexpramipexole (50 mg/day or 300 mg/day), subjects received twice daily doses of placebo for up to 18 months.
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Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
Ostatní jména:
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Časové okno: 12 weeks
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Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group.
Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group.
Patients are only counted once per criterion per laboratory test.
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12 weeks
|
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Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group
Časové okno: 12 weeks
|
Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group.
Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group.
Patients are only counted once per criterion per laboratory test.
|
12 weeks
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Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
Časové okno: 12 weeks
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Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group.
Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
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12 weeks
|
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Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
Časové okno: 12 weeks
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Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group.
Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
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12 weeks
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group
Časové okno: 12 weeks
|
The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills.
There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48, with higher scores representing better function.
Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis ALSFRS-R score.
Units for slope are change per month in units on the ALSFRS-R scale.
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12 weeks
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Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group
Časové okno: 12 weeks
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Slope of change in Upright Vital Capacity (percent predicted upright vital capacity) from Baseline to Week 12.
A negative change/slope indicates clinical worsening.
Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis as percent predicted upright vital capacity.
Units for slope are change per month in percent predicted upright vital capacity.
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12 weeks
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Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology
Časové okno: 4 weeks
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Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group.
Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group.
Patients are only counted once per criterion per laboratory test.
|
4 weeks
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Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results
Časové okno: 4 weeks
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Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group.
Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group.
Patients are only counted once per criterion per laboratory test.
|
4 weeks
|
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Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings
Časové okno: 4 weeks
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Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group.
Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
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4 weeks
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Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements
Časové okno: 4 weeks
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Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group.
Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
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4 weeks
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Part 2 Placebo Washout: Absolute Change in ALSFRS-R Total Score
Časové okno: 4 weeks
|
The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48, with higher scores representing better function. Units are points on the ALSFRS-R score as an absolute change from the baseline of the placebo washout to week 4 of the placebo washout. |
4 weeks
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Part 2 Placebo Washout: Absolute Change in Upright Vital Capacity (Percent Predicted) From Baseline to End of Placebo Washout (Week 4)
Časové okno: 4 weeks
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Absolute change in Upright Vital Capacity From Baseline to Week 4. Units are percent of predicted Upright Vital Capacity.
A negative change indicates clinical worsening.
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4 weeks
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Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Časové okno: up to 76 weeks
|
Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group.
Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group.
Patients are only counted once per criterion per parameter.
|
up to 76 weeks
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Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group
Časové okno: up to 76 weeks
|
Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group.
Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group.
Patients are only counted once per criterion per parameter.
|
up to 76 weeks
|
|
Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
Časové okno: up to 76 weeks
|
Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group.
Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group.
Patients are only counted once per criterion per parameter.
|
up to 76 weeks
|
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Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
Časové okno: up to 76 weeks
|
Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group.
Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group.
Patients are only counted once per criterion per parameter.
|
up to 76 weeks
|
|
Part 2 Double-Blind Treatment: Slope of the ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 28 by Treatment Group
Časové okno: 28 weeks
|
The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills.
There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48, with higher scores representing better function.
Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis ALSFRS-R score.
Units for slope are change per month n units on the ALSFRS-R scale.
|
28 weeks
|
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Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group
Časové okno: Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2
|
Slope of Upright Vital Capacity (percent predicted) through Week 28.
A negative change indicates clinical worsening.
Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis percent predicted upright vital capacity.
Units for slope are change per month in percent predicted upright vital capacity.
|
Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
9. dubna 2008
Primární dokončení (Aktuální)
31. července 2009
Dokončení studie (Aktuální)
4. září 2009
Termíny zápisu do studia
První předloženo
26. března 2008
První předloženo, které splnilo kritéria kontroly kvality
28. března 2008
První zveřejněno (Odhad)
31. března 2008
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
8. července 2021
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
16. června 2021
Naposledy ověřeno
1. března 2021
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Patologické procesy
- Metabolické choroby
- Onemocnění centrálního nervového systému
- Nemoci nervového systému
- Neuromuskulární onemocnění
- Neurodegenerativní onemocnění
- Nemoci míchy
- Proteinopatie TDP-43
- Nedostatky proteostázy
- Skleróza
- Nemoc motorických neuronů
- Amyotrofní laterální skleróza
- Fyziologické účinky léků
- Neurotransmiterové látky
- Molekulární mechanismy farmakologického působení
- Ochranné prostředky
- Agonisté dopaminu
- Dopaminové látky
- Antioxidanty
- Antiparkinsonoví agenti
- Činidla proti dyskinézi
- Pramipexol
Další identifikační čísla studie
- KNS-760704-CL201
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .