Optimism in IBM: a dbRCT Phase III trial of sirolimus in patients with IBM to slow disease progression as measured by the IBM functional rating scale (IBM-FRS)

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This double-blind, placebo-controlled, multicenter phase-3 study will explore the efficacy of sirolimus as novel approach to treat Inclusion Body Myositis (IBM), a chronic inflammatory myopathy of unknown cause. No drug is capable in IBM to hold the progressive loss of muscle mass and strength, which strongly reduces the quality of life and impairs ambulation, swallowing, and social participation. The disease pathology includes inflammation and degeneration of skeletal muscle fibers. It is hypothesized that sirolimus may intercept the inflammatory and degenerative cascades by modulation of the impaired autophagy in skeletal muscle and, thus, lessen muscle damage, promote repair and enhance muscle strength. Sirolimus is a well-established immunosuppressant for organ transplantation and has recently demonstrated some beneficial effects on secondary outcome measures in a placebo-controlled, double-blind phase 2 trial in IBM. In the present study, 140 patients will be recruited globally at sites in Australia, USA and Europe. The study is facilitated by a highly competitive grant awarded by the Australian Science foundation. The grant will cover expenses for Australian sites and cross-country costs such as electronic case reporting. Despite the excellent international study settings, there is an inevitable need for national funding. Lack of national funding will pose an imminent threat to the feasibility of the global trial. The present proposal aims to request funding for the German contribution to the global trial. Intervention of the international trial consists of 2 mg sirolimus orally for 84 weeks compared to placebo. Primary outcome measure is the slowing of disease progression, assessed by the mean change in the disease specific, validated functional scale IBM-FRS from baseline to week 84. Secondary outcome measures include safety and tolerability and additional clinically meaningful functional tests, such as the 6-minute walking distance, modified timed up-and-go, and muscle strength. It is expected that the international study including the German patients will solidify previous observations on sirolimus in IBM in order to identify the first effective treatment for this devastating disease.