Safety and Tolerability Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS) (CL201)
16 de junho de 2021 atualizado 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.
Visão geral do estudo
Status
Concluído
Condições
Descrição detalhada
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 estudo
Intervencional
Inscrição (Real)
194
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Arkansas
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Little Rock, Arkansas, Estados Unidos, 72205
- University of Arkansas for Medical Sciences
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California
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Los Angeles, California, Estados Unidos, 90095
- UCLA, Dept. of Neurology - Neuromuscular/ALS Research Center
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San Francisco, California, Estados Unidos, 94115
- The Forbes Norris MDA/ALS Research Center
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- University of Colorado Health Sciences Center
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Florida
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Miami, Florida, Estados Unidos, 33136
- University of Miami Miller School of Medicine
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Kansas
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Kansas City, Kansas, Estados Unidos, 66160
- University of Kansas Medical Center
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Maryland
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Baltimore, Maryland, Estados Unidos, 21228
- Johns Hopkins University School Of Medicine
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02129
- Massachusettes General Hospital
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Missouri
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Saint Louis, Missouri, Estados Unidos, 63110
- Washington University School of Medicine
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Nebraska
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Lincoln, Nebraska, Estados Unidos, 68506
- Bryan LGH Medical Center East
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New York
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New York, New York, Estados Unidos, 10032
- Columbia University, Lou Gehrig MDA/ALS Research Center
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Syracuse, New York, Estados Unidos, 13210
- SUNY Upstate Medical University
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Oregon
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Portland, Oregon, Estados Unidos, 97239
- Oregon Health Sciences University
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Pennsylvania
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Hershey, Pennsylvania, Estados Unidos, 17033
- Penn State Hershey Medical Center
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Philadelphia, Pennsylvania, Estados Unidos, 19102
- Drexel University College of Medicine
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Pittsburgh, Pennsylvania, Estados Unidos, 15213
- University of Pittsburgh School of Medicine
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37232
- Vanderbilt University Medical Center
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Texas
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San Antonio, Texas, Estados Unidos, 78229
- University of Texas Health Sciences Center of San Antonio
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Utah
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Salt Lake City, Utah, Estados Unidos, 84132
- University of Utah
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Virginia
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Charlottesville, Virginia, Estados Unidos, 22908
- University of Virginia Health System
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Washington
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Seattle, Washington, Estados Unidos, 98195
- University of Washington
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
21 anos a 80 anos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Comparador de 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.
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Placebo: 2 tablets taken orally twice daily
Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
Outros nomes:
Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily
Outros nomes:
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Outros nomes:
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Experimental: 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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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.
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Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
Outros nomes:
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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.
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4 weeks
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Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings
Prazo: 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
Prazo: 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
Prazo: 4 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. 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)
Prazo: 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
Prazo: 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.
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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
Prazo: up to 76 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 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
Prazo: up to 76 weeks
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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
Prazo: up to 76 weeks
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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
Prazo: 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
Prazo: 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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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Publicações e links úteis
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Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
9 de abril de 2008
Conclusão Primária (Real)
31 de julho de 2009
Conclusão do estudo (Real)
4 de setembro de 2009
Datas de inscrição no estudo
Enviado pela primeira vez
26 de março de 2008
Enviado pela primeira vez que atendeu aos critérios de CQ
28 de março de 2008
Primeira postagem (Estimativa)
31 de março de 2008
Atualizações de registro de estudo
Última Atualização Postada (Real)
8 de julho de 2021
Última atualização enviada que atendeu aos critérios de controle de qualidade
16 de junho de 2021
Última verificação
1 de março de 2021
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Processos Patológicos
- Doenças Metabólicas
- Doenças do Sistema Nervoso Central
- Doenças do Sistema Nervoso
- Doenças Neuromusculares
- Doenças Neurodegenerativas
- Doenças da Medula Espinhal
- Proteinopatias TDP-43
- Deficiências de Proteostase
- Esclerose
- Doença do neurônio motor
- Esclerose Lateral Amiotrófica
- Efeitos Fisiológicos das Drogas
- Agentes Neurotransmissores
- Mecanismos Moleculares de Ação Farmacológica
- Agentes de proteção
- Agonistas de Dopamina
- Agentes de Dopamina
- Antioxidantes
- Agentes antiparkinsonianos
- Agentes Antidiscinesia
- Pramipexol
Outros números de identificação do estudo
- KNS-760704-CL201
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .