Safety and tolerability of RJx-01 to maintain muscle integrity in patients following hospitalisation with an acute exacerbation of COPD (MINT-COPD): protocol for a phase IIa randomised double-blind placebo-controlled trial

Introduction Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of global disability and disability-adjusted life years. One of the key systemic features of COPD is impaired skeletal muscle mass and function, termed sarcopenia. The recognition of skeletal muscle dysfunction as a treatable trait in COPD opens a therapeutic avenue for pharmacological development, with the aim of improving physical function and reducing healthcare utilisation. A novel combination drug, RJx-01, was identified as a candidate therapy for sarcopenia based on preclinical evidence. The primary aim of this study is to evaluate the safety and tolerability of RJx-01 compared with placebo following hospitalisation with an acute exacerbation of COPD (AECOPD), when acute deterioration of skeletal muscle integrity is observed. Exploratory efficacy analyses will assess differences in muscle function, mass, and multi-omic-derived outcomes. Methods and analysis The MINT-COPD trial is a phase IIa, single centre, randomised controlled trial (RCT). Eighty participants admitted to hospital with AECOPD will be randomly assigned 1:1 to receive either oral RJx-01 or placebo, once daily for 24 weeks. The primary outcome is safety and tolerability of RJx-01 compared with placebo in COPD patients. Exploratory objectives aim to assess the preliminary effects of AECOPD-associated hospitalisation and RJx-01 treatment on muscle mass, function, and fatiguability, as well as patient reported symptoms and frailty. The optional skeletal muscle biopsy sub-study aims to assess the effects of AECOPD on proteomic and transcriptomic markers of skeletal muscle.