Safety and Tolerability Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS) (CL201)
16. juni 2021 opdateret af: 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.
Studieoversigt
Status
Afsluttet
Betingelser
Detaljeret beskrivelse
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).
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
194
Fase
- Fase 2
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Arkansas
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Little Rock, Arkansas, Forenede Stater, 72205
- University of Arkansas for Medical Sciences
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California
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Los Angeles, California, Forenede Stater, 90095
- UCLA, Dept. of Neurology - Neuromuscular/ALS Research Center
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San Francisco, California, Forenede Stater, 94115
- The Forbes Norris MDA/ALS Research Center
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Colorado
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Aurora, Colorado, Forenede Stater, 80045
- University of Colorado Health Sciences Center
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Florida
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Miami, Florida, Forenede Stater, 33136
- University of Miami Miller School of Medicine
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Kansas
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Kansas City, Kansas, Forenede Stater, 66160
- University of Kansas Medical Center
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Maryland
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Baltimore, Maryland, Forenede Stater, 21228
- Johns Hopkins University School Of Medicine
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02129
- Massachusettes General Hospital
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Missouri
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Saint Louis, Missouri, Forenede Stater, 63110
- Washington University School of Medicine
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Nebraska
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Lincoln, Nebraska, Forenede Stater, 68506
- Bryan LGH Medical Center East
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New York
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New York, New York, Forenede Stater, 10032
- Columbia University, Lou Gehrig MDA/ALS Research Center
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Syracuse, New York, Forenede Stater, 13210
- SUNY Upstate Medical University
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Oregon
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Portland, Oregon, Forenede Stater, 97239
- Oregon Health Sciences University
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Pennsylvania
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Hershey, Pennsylvania, Forenede Stater, 17033
- Penn State Hershey Medical Center
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Philadelphia, Pennsylvania, Forenede Stater, 19102
- Drexel University College of Medicine
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Pittsburgh, Pennsylvania, Forenede Stater, 15213
- University of Pittsburgh School of Medicine
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Tennessee
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Nashville, Tennessee, Forenede Stater, 37232
- Vanderbilt University Medical Center
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Texas
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San Antonio, Texas, Forenede Stater, 78229
- University of Texas Health Sciences Center of San Antonio
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Utah
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Salt Lake City, Utah, Forenede Stater, 84132
- University of Utah
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Virginia
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Charlottesville, Virginia, Forenede Stater, 22908
- University of Virginia Health System
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Washington
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Seattle, Washington, Forenede Stater, 98195
- University of Washington
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
21 år til 80 år (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
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
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Placebo komparator: 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
Andre navne:
Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily
Andre navne:
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Andre navne:
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Eksperimentel: 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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Eksperimentel: 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
Andre navne:
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Tidsramme: 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
Tidsramme: 12 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.
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12 weeks
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Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
Tidsramme: 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
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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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
Tidsramme: 12 weeks
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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
Tidsramme: 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
Tidsramme: 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.
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4 weeks
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Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: up to 76 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 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
Tidsramme: 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
|
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Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
Tidsramme: 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
Tidsramme: 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
|
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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
Tidsramme: 28 weeks
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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.
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28 weeks
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Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group
Tidsramme: Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2
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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.
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Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
9. april 2008
Primær færdiggørelse (Faktiske)
31. juli 2009
Studieafslutning (Faktiske)
4. september 2009
Datoer for studieregistrering
Først indsendt
26. marts 2008
Først indsendt, der opfyldte QC-kriterier
28. marts 2008
Først opslået (Skøn)
31. marts 2008
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
8. juli 2021
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
16. juni 2021
Sidst verificeret
1. marts 2021
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Patologiske processer
- Metaboliske sygdomme
- Sygdomme i centralnervesystemet
- Sygdomme i nervesystemet
- Neuromuskulære sygdomme
- Neurodegenerative sygdomme
- Rygmarvssygdomme
- TDP-43 Proteinopatier
- Proteostase mangler
- Sclerose
- Motor neuron sygdom
- Amyotrofisk lateral sklerose
- Lægemidlers fysiologiske virkninger
- Neurotransmittermidler
- Molekylære mekanismer for farmakologisk virkning
- Beskyttelsesagenter
- Dopaminagonister
- Dopaminmidler
- Antioxidanter
- Antiparkinson-midler
- Midler mod dyskinesi
- Pramipexol
Andre undersøgelses-id-numre
- KNS-760704-CL201
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .