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

16. Juni 2021 aktualisiert von: 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.

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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).

Studientyp

Interventionell

Einschreibung (Tatsächlich)

194

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

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

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

21 Jahre bis 80 Jahre (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Vervierfachen

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
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.
Arzneimittel: Placebo
Placebo: 2 tablets taken orally twice daily
Arzneimittel: Dexpramipexole 50 mg/day
Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
Andere Namen:
  • KNS-760704
  • BIIB050
Arzneimittel: Dexpramipexole 150 mg/day
Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily
Andere Namen:
  • KNS-760704
  • BIIB050
Arzneimittel: Dexpramipexole 300 mg/day
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Andere Namen:
  • KNS-760704
  • BIIB050
Experimental: Part 2: Placebo washout
At the beginning of Part 2, subjects received twice daily doses of placebo for approximately 4 weeks.
Arzneimittel: Placebo
Placebo: 2 tablets taken orally twice daily
Experimental: 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.
Arzneimittel: Dexpramipexole 50 mg/day
Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
Andere Namen:
  • KNS-760704
  • BIIB050
Arzneimittel: Dexpramipexole 300 mg/day
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Andere Namen:
  • KNS-760704
  • BIIB050

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Knopp Biosciences

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

9. April 2008

Primärer Abschluss (Tatsächlich)

31. Juli 2009

Studienabschluss (Tatsächlich)

4. September 2009

Studienanmeldedaten

Zuerst eingereicht

26. März 2008

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

28. März 2008

Zuerst gepostet (Schätzen)

31. März 2008

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

8. Juli 2021

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

16. Juni 2021

Zuletzt verifiziert

1. März 2021

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • KNS-760704-CL201

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