Esta página se tradujo automáticamente y no se garantiza la precisión de la traducción. por favor refiérase a versión inglesa para un texto fuente.

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

16 de junio de 2021 actualizado por: 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.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

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 de estudio

Intervencionista

Inscripción (Actual)

194

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

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

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

21 años a 80 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador de placebos: 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
Otros nombres:
  • KNS-760704
  • BIIB050
Droga: Dexpramipexole 150 mg/day
Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily
Otros nombres:
  • KNS-760704
  • BIIB050
Droga: Dexpramipexole 300 mg/day
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Otros nombres:
  • 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.
Droga: 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.
Droga: Dexpramipexole 50 mg/day
Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
Otros nombres:
  • KNS-760704
  • BIIB050
Droga: Dexpramipexole 300 mg/day
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Otros nombres:
  • KNS-760704
  • BIIB050

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Knopp Biosciences

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

9 de abril de 2008

Finalización primaria (Actual)

31 de julio de 2009

Finalización del estudio (Actual)

4 de septiembre de 2009

Fechas de registro del estudio

Enviado por primera vez

26 de marzo de 2008

Primero enviado que cumplió con los criterios de control de calidad

28 de marzo de 2008

Publicado por primera vez (Estimar)

31 de marzo de 2008

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

8 de julio de 2021

Última actualización enviada que cumplió con los criterios de control de calidad

16 de junio de 2021

Última verificación

1 de marzo de 2021

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • KNS-760704-CL201

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

Suscribir