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Safety and Tolerability Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS) (CL201)

16 giugno 2021 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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).

Tipo di studio

Interventistico

Iscrizione (Effettivo)

194

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • Arkansas
      • Little Rock, Arkansas, Stati Uniti, 72205
        • University of Arkansas for Medical Sciences
    • California
      • Los Angeles, California, Stati Uniti, 90095
        • UCLA, Dept. of Neurology - Neuromuscular/ALS Research Center
      • San Francisco, California, Stati Uniti, 94115
        • The Forbes Norris MDA/ALS Research Center
    • Colorado
      • Aurora, Colorado, Stati Uniti, 80045
        • University of Colorado Health Sciences Center
    • Florida
      • Miami, Florida, Stati Uniti, 33136
        • University of Miami Miller School of Medicine
    • Kansas
      • Kansas City, Kansas, Stati Uniti, 66160
        • University of Kansas Medical Center
    • Maryland
      • Baltimore, Maryland, Stati Uniti, 21228
        • Johns Hopkins University School Of Medicine
    • Massachusetts
      • Boston, Massachusetts, Stati Uniti, 02129
        • Massachusettes General Hospital
    • Missouri
      • Saint Louis, Missouri, Stati Uniti, 63110
        • Washington University School of Medicine
    • Nebraska
      • Lincoln, Nebraska, Stati Uniti, 68506
        • Bryan LGH Medical Center East
    • New York
      • New York, New York, Stati Uniti, 10032
        • Columbia University, Lou Gehrig MDA/ALS Research Center
      • Syracuse, New York, Stati Uniti, 13210
        • SUNY Upstate Medical University
    • Oregon
      • Portland, Oregon, Stati Uniti, 97239
        • Oregon Health Sciences University
    • Pennsylvania
      • Hershey, Pennsylvania, Stati Uniti, 17033
        • Penn State Hershey Medical Center
      • Philadelphia, Pennsylvania, Stati Uniti, 19102
        • Drexel University College of Medicine
      • Pittsburgh, Pennsylvania, Stati Uniti, 15213
        • University of Pittsburgh School of Medicine
    • Tennessee
      • Nashville, Tennessee, Stati Uniti, 37232
        • Vanderbilt University Medical Center
    • Texas
      • San Antonio, Texas, Stati Uniti, 78229
        • University of Texas Health Sciences Center of San Antonio
    • Utah
      • Salt Lake City, Utah, Stati Uniti, 84132
        • University of Utah
    • Virginia
      • Charlottesville, Virginia, Stati Uniti, 22908
        • University of Virginia Health System
    • Washington
      • Seattle, Washington, Stati Uniti, 98195
        • University of Washington

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 21 anni a 80 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore placebo: 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.
Droga: Placebo
Placebo: 2 tablets taken orally twice daily
Droga: Dexpramipexole 50 mg/day
Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
Altri nomi:
  • KNS-760704
  • BIIB050
Droga: Dexpramipexole 150 mg/day
Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily
Altri nomi:
  • KNS-760704
  • BIIB050
Droga: Dexpramipexole 300 mg/day
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Altri nomi:
  • KNS-760704
  • BIIB050
Sperimentale: Part 2: Placebo washout
At the beginning of Part 2, subjects received twice daily doses of placebo for approximately 4 weeks.
Droga: Placebo
Placebo: 2 tablets taken orally twice daily
Sperimentale: 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.
Droga: Dexpramipexole 50 mg/day
Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
Altri nomi:
  • KNS-760704
  • BIIB050
Droga: Dexpramipexole 300 mg/day
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Altri nomi:
  • KNS-760704
  • BIIB050

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Lasso di tempo: 12 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 laboratory test.
12 weeks
Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group
Lasso di tempo: 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
Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
Lasso di tempo: 12 weeks
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.
12 weeks
Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
Lasso di tempo: 12 weeks
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.
12 weeks

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group
Lasso di tempo: 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.
12 weeks
Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group
Lasso di tempo: 12 weeks
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.
12 weeks
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology
Lasso di tempo: 4 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 laboratory test.
4 weeks
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results
Lasso di tempo: 4 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.
4 weeks
Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings
Lasso di tempo: 4 weeks
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.
4 weeks
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements
Lasso di tempo: 4 weeks
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.
4 weeks
Part 2 Placebo Washout: Absolute Change in ALSFRS-R Total Score
Lasso di tempo: 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
Part 2 Placebo Washout: Absolute Change in Upright Vital Capacity (Percent Predicted) From Baseline to End of Placebo Washout (Week 4)
Lasso di tempo: 4 weeks
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.
4 weeks
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Lasso di tempo: 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
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group
Lasso di tempo: 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
Lasso di tempo: 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
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
Lasso di tempo: 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
Lasso di tempo: 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
Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Knopp Biosciences

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

9 aprile 2008

Completamento primario (Effettivo)

31 luglio 2009

Completamento dello studio (Effettivo)

4 settembre 2009

Date di iscrizione allo studio

Primo inviato

26 marzo 2008

Primo inviato che soddisfa i criteri di controllo qualità

28 marzo 2008

Primo Inserito (Stima)

31 marzo 2008

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

8 luglio 2021

Ultimo aggiornamento inviato che soddisfa i criteri QC

16 giugno 2021

Ultimo verificato

1 marzo 2021

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • KNS-760704-CL201

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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