Design and rationale for a randomized, double-blind, placebo-controlled Phase 2/3 trial of oral arimoclomol in inclusion body myositis

Ethical publication statement We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Disclosure of conflicts of interest P.M.M. has received consulting fees and funding support from Orphazyme A/S, paid to his academic institution (University College London), for the oversight and conduct of this study. R.J.B. has received funding from the FDA Office Orphan Products Development grant for his role in this study. M.P.M. has no relevant conflicts of interest to declare. C.S. and T.B. are employees of Orphazyme A/S. M.G.H. receives research funding from the Medical Research Council UK and has previously acted a consultant for Novartis and for Orphazyme A/S. M.M.D. is a consultant for Orphazyme and received funding support, paid to his academic institution (University of Kansas Medical Center, Research Institute), from Orphazyme A/S for the oversight and conduct of this study. Design and rationale for a randomized, double-blind, placebo-controlled Phase 2/3 trial of oral arimoclomol in inclusion body myositis Abstract Introduction/Aims: Inclusion body myositis (IBM) is the most common progressive, debilitating muscle disease in people over the age of 50 years, for whom there is no effective treatment. Here, we present the design and rationale for one of the largest clinical studies conducted in IBM to date, to evaluate the efficacy, safety, and tolerability of arimoclomol, a novel, oral amplifier of the cellular heat shock response. Methods: This is a randomized, double-blind, placebo-controlled, parallel group trial conducted at 11 centers in the US and one center in the UK. Eligible patients had a diagnosis of IBM fulfilling European Neuromuscular Centre 2011 criteria, with onset of weakness at > 45 years of age. Enrolled participants were randomized 1:1 to receive either oral arimoclomol citrate 1,200 mg/day or matching placebo for up to 20 months. The primary endpoint is the change from baseline to Month 20 in the IBM functional rating scale (IBMFRS) total score. The secondary efficacy endpoints include evaluations of participants’ functional abilities, strength, and physical health-related quality of life (HRQoL). A sub-study will characterize muscle changes using MRI in a subset of participants. Discussion: This study will generate important clinical data on a novel therapeutic strategy for patients with IBM, a population with no current treatment options.