A 24-Week, Phase III, Double-Blind, Parallel-Group Study of Edaravone (MCI-186) for Treatment of Amyotrophic Lateral Sclerosis (ALS) (P3.189)

Abstract

Objective:To investigate the efficacy and safety of edaravone versus placebo in a more narrowly defined population of patients (Edaravone MCI-186-J19/NCT01492686), intended to replicate the findings of a previous post hoc analysis. Background:The efficacy of edaravone was previously evaluated in a randomized placebo controlled phase III study (Abe K et al. Amyotroph Lateral Scler Frontotemporal Degener 2014; 15: 610-7). This study did not demonstrate efficacy versus placebo of edaravone as an investigative treatment for ALS, but hypothesis-driven post hoc analyses suggested an opportunity to demonstrate efficacy in a more narrowly defined patient population. Design/Methods: 137 patients were randomized 1:1 to receive edaravone or placebo following a 12-week pre-observation period. Selection criteria included: Definite or Probable ALS (El Escorial/revised Airlie House); Japan ALS severity classification grade<3; scoring≥2 points on each single ALSFRS-R item at screening; [percnt] forced vital capacity≥80[percnt]; and ALS duration≤2 years. Treatment consisted of 6 cycles of 60-mg edaravone/matching placebo treatment. Primary efficacy endpoint was change in ALS Functional Rating Scale-Revised (ALSFRS-R) score at week 24. Secondary endpoints included change in ALS Assessment Questionnaire (ALSAQ40) scores. Safety endpoints included adverse events (AEs) and laboratory tests. Results:Mean change (±SE) in ALSFRS-R score was -7.50±0.66 (placebo) and -5.01±0.64 (edaravone): a between group difference of 2.49±0.76 (P=0.001). Between group difference for ALSAQ40 was -8.79±4.03 (P=0.031). Both groups showed similar AE incidence (84.1[percnt] edaravone, 83.8[percnt] placebo). Incidence of serious AEs was 15.9[percnt] (edaravone) and 23.5[percnt] (placebo). The most common AEs were contusion, and dysphagia (16[percnt] and 13[percnt] of patients, respectively). Incidence of adverse drug reactions (ADRs) was 2.9[percnt] (edaravone) and 7.4[percnt] (placebo). There were no serious ADRs and no AEs that lead to death. Conclusion:Edaravone treated ALS patients meeting the protocol inclusion criteria had less functional loss at 6 months, and had less quality of life deterioration compared to those receiving standard of care.

Disclosure: Dr. Tanaka has received personal compensation for activities with Mitsubishi Tanabe Pharma Corporation. Dr. Sakata has received personal compensation for activities with the Mitsubishi Tanabe Pharmaceutical Corporation. Dr. Palumbo has received personal compensation for activities with Mitsubishi Tanabe Pharma Corporation. Dr. Akimoto has received personal compensation for activities with Mitsubishi Tanabe Pharma Corporation.