MN-166 (ibudilast) in Amyotrophic Lateral Sclerosis in a Phase IIb/III Study: COMBAT-ALS Study Design

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with motor neuron loss as a defining feature. Despite significant effort, therapeutic breakthroughs have been modest. MN-166 (ibudilast) has demonstrated neuroprotective action by various mechanisms: inhibition of proinflammatory cytokines and macrophage migration inhibitory factor, phosphodiesterase inhibition, and attenuation of glial cell activation in models of ALS. Early-phase studies suggest that MN-166 may improve survival outcomes and slow disease progression in patients with ALS. This article describes the rationale and design of COMBAT-ALS, an ongoing randomized, double-blind, placebo-controlled, multicenter Phase IIb/III study in ALS. This study is designed to evaluate the pharmacokinetics, safety and tolerability and assess the efficacy of MN-166 on function, muscle strength, quality of life and survival in ALS.Lay abstract Amyotrophic lateral sclerosis (ALS) is a neurological disease defined by the loss of the nerve cells going to the muscles. Despite significant effort, we still do not have good treatments for ALS. MN-166 (ibudilast) can protect nerve cells by calming inflammation in several ways in models of ALS. Early human studies suggest that MN-166 may extend life and slow disease progression in ALS patients. This article describes the rationale and design of COMBAT-ALS, an ongoing randomized, double-blind, placebo-controlled, multicenter Phase IIb/III study. This study will show the drug’s safety and tolerability and its effects on physical function, muscle strength, quality of life and survival in people living with ALS. Trial registration number: NCT04057898 (ClinicalTrial.gov).