Post-hoc analyses of the edaravone clinical trials Study 16 and Study 19: a step toward more efficient clinical trial designs in amyotrophic lateral sclerosis.
Amyotroph Lateral Scler Frontotemporal Degener
; 20(5-6): 421-431, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-30982356
ABSTRACT
Objectives:
The edaravone development program established a study design in which a treatment effect slowing functional loss in amyotrophic lateral sclerosis (ALS) could be documented within a 24-week time frame. This report elucidates the strategic enrichment design utilized to create efficiency and precision in the development program.Methods:
Post-hoc analyses describe learning, sequential iteration, and evolution in study design.Results:
The first Phase 3 study of edaravone in ALS (Study MCI186-16) included a large proportion (35%) of placebo patients who were minimal progressors. These patients demonstrated high heterogeneity in change in ALSFRS-R score (-4 median with interquartile range [IQR] 7.5) and a modal distribution score of 0, suggesting evidence of minimal change in ALSFRS-R during the study. This level of variability and rate of progression may have made it difficult to detect a prospective treatment effect in the study. A strategic enrichment strategy provided the second Phase 3 study (Study MCI186-19) with the ability to detect a treatment effect. In Study MCI186-19, only 13% of the placebo patients were minimal progressors. Further, these placebo patients demonstrated less heterogeneity and greater functional progression of ALS, thereby providing greater likelihood of detecting a treatment effect. The enrichment strategy may have excluded some rapidly progressing patients, potentially supporting the detection of a treatment effect. As previously published, Study MCI186-19 prospectively documented a 33% reduction in rate of progression of ALS (p = 0.0013).Conclusions:
Strategic choices in the design of Study MCI186-19 reduced the proportion of minimally progressing patients and supported detection of a treatment effect.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ensaios Clínicos Controlados Aleatórios como Assunto
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Ensaios Clínicos Fase III como Assunto
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Ensaios Clínicos Fase II como Assunto
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Fármacos Neuroprotetores
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Edaravone
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Esclerose Lateral Amiotrófica
Tipo de estudo:
Clinical_trials
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Systematic_reviews
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article