Background: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder. The urgent need for more effective therapies has led investigators to modify various aspects of traditional ALS clinical trial design with the goal of reducing sample size, study duration, and risk to patients, while enhancing statistical power and overall study efficiency. Diagnostic delay in ALS makes it challenging to uniformly enroll patients in the early stages of disease, however analysis of data from existing databases and clinical trial resources may help identify predictors of disease progression and ensure a more homogenous patient cohort to improve statistical powering. The Phase 2 CENTAUR trial evaluated the safety and tolerability of AMX0035 in patients with ALS. This trial utilized the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database to identify key inclusion criteria with the goal of selecting a rapidly progressing, homogenous patient cohort.
Results: Evaluation of the PRO-ACT database, and existing clinical trial resources, identified time since symptom onset and El Escorial criteria as strong predictors of disease progression in previously conducted clinical trials. The recently completed CENTAUR trial utilized <18 months from ALS symptom onset and Definite ALS (El Escorial criteria) as 2 key inclusion criteria. Analysis demonstrates that these patient cohort demographics were able to successfully select for a rapidly progressing, homogenous patient cohort.
Conclusions: Thoughtful and data-driven inclusion/exclusion criteria can stratify trial participants to allow for rapid, highly-powered Phase 2 clinical trials. Evaluation of the PRO-ACT database, and existing clinical trial resources, allow for the identification of trial criteria, particularly time since symptom onset and El Escorial criteria, as strong predictors of disease progression in previously conducted clinical trials.