Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial

Inclusion body myositis is an idiopathic inflammatory myopathy and the most common myopathy affecting people older than 50 years. To date, there are no effective drug treatments. We aimed to assess the safety, efficacy, and tolerability of bimagrumab—a fully human monoclonal antibody—in individuals...

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Published in:	Lancet neurology 2019-09, Vol.18 (9), p.834-844
Main Authors:	Hanna, Michael G, Badrising, Umesh A, Benveniste, Olivier, Lloyd, Thomas E, Needham, Merrilee, Chinoy, Hector, Aoki, Masashi, Machado, Pedro M, Liang, Christina, Reardon, Katrina A, de Visser, Marianne, Ascherman, Dana P, Barohn, Richard J, Dimachkie, Mazen M, Miller, James A L, Kissel, John T, Oskarsson, Björn, Joyce, Nanette C, Van den Bergh, Peter, Baets, Jonathan, De Bleecker, Jan L, Karam, Chafic, David, William S, Mirabella, Massimiliano, Nations, Sharon P, Jung, Hans H, Pegoraro, Elena, Maggi, Lorenzo, Rodolico, Carmelo, Filosto, Massimiliano, Shaibani, Aziz I, Sivakumar, Kumaraswamy, Goyal, Namita A, Mori-Yoshimura, Madoka, Yamashita, Satoshi, Suzuki, Naoki, Katsuno, Masahisa, Murata, Kenya, Nodera, Hiroyuki, Nishino, Ichizo, Romano, Carla D, Williams, Valerie S L, Vissing, John, Auberson, Lixin Zhang, Wu, Min, de Vera, Ana, Papanicolaou, Dimitris A, Amato, Anthony A
Format:	Article
Language:	eng
Subjects:	Adenocarcinoma Antidepressants Clinical trials Diarrhea Double-blind studies Echocardiography EKG Inflammation Inflammatory diseases Intravenous administration Life Sciences Lung cancer Medical research Monoclonal antibodies Musculoskeletal diseases Musculoskeletal system Myocardial infarction Myopathy Myositis Overdose Safety Sedatives Systematic review Urinalysis
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Summary:	Inclusion body myositis is an idiopathic inflammatory myopathy and the most common myopathy affecting people older than 50 years. To date, there are no effective drug treatments. We aimed to assess the safety, efficacy, and tolerability of bimagrumab—a fully human monoclonal antibody—in individuals with inclusion body myositis. We did a multicentre, double-blind, placebo-controlled study (RESILIENT) at 38 academic clinical sites in Australia, Europe, Japan, and the USA. Individuals (aged 36–85 years) were eligible for the study if they met modified 2010 Medical Research Council criteria for inclusion body myositis. We randomly assigned participants (1:1:1:1) using a blocked randomisation schedule (block size of four) to either bimagrumab (10 mg/kg, 3 mg/kg, or 1 mg/kg) or placebo matched in appearance to bimagrumab, administered as intravenous infusions every 4 weeks for at least 48 weeks. All study participants, the funder, investigators, site personnel, and people doing assessments were masked to treatment assignment. The primary outcome measure was 6-min walking distance (6MWD), which was assessed at week 52 in the primary analysis population and analysed by intention-to-treat principles. We used a multivariate normal repeated measures model to analyse data for 6MWD. Safety was assessed by recording adverse events and by electrocardiography, echocardiography, haematological testing, urinalysis, and blood chemistry. This trial is registered with ClinicalTrials.gov, number NCT01925209; this report represents the final analysis. Between Sept 26, 2013, and Jan 6, 2016, 251 participants were enrolled to the study, of whom 63 were assigned to each bimagrumab group and 62 were allocated to the placebo group. At week 52, 6MWD change from baseline did not differ between any bimagrumab dose and placebo (least squares mean treatment difference for bimagrumab 10 mg/kg group, 17·6 m, SE 14·3, 99% CI –19·6 to 54·8; p=0·22; for 3 mg/kg group, 18·6 m, 14·2, –18·2 to 55·4; p=0·19; and for 1 mg/kg group, –1·3 m, 14·1, –38·0 to 35·4; p=0·93). 63 (100%) participants in each bimagrumab group and 61 (98%) of 62 in the placebo group had at least one adverse event. Falls were the most frequent adverse event (48 [76%] in the bimagrumab 10 mg/kg group, 55 [87%] in the 3 mg/kg group, 54 [86%] in the 1 mg/kg group, and 52 [84%] in the placebo group). The most frequently reported adverse events with bimagrumab were muscle spasms (32 [51%] in the bimagrumab 10 mg/kg group, 43 [68%]
ISSN:	1474-4422 1474-4465