Sirukumab

Sirukumab is a human anti-IL-6 monoclonal antibody that selectively binds to the cytokine with high affinity that may have therapeutic benefit in the treatment of polymyalgia rheumatica (PMR) by interrupting multiple pathogenic pathways. Sirukumab inhibits IL-6-mediated signal transducer and activator of transcription 3 (STAT3) phosphorylation, resulting in the inhibition of the biological effect of IL-6. This study will evaluate the efficacy and safety of sirukumab to characterize the benefit-to-risk profile of sirukumab in the treatment of active PMR. The study will be conducted in 2 parts (Part A and Part B) and consists of the following phases: Screening phase, Part A: 52-week double-blind treatment phase, Part B: 52-week extension phase with no study drug administration and a 16-week follow-up phase if applicable.
Approximately 150 subjects with a diagnosis of PMR and active disease within 6 weeks of baseline will be randomized into Part A, the 52-week double-blind treatment phase, to receive one of two doses of sirukumab or placebo, each in addition to a pre-specified prednisone taper. The efficacy and safety of sirukumab in sustaining remission will be assessed at Week 52. Subjects completing Part A of the study who are in clinical remission will be eligible to enter Part B, the 52-week extension phase, designed to investigate the long-term maintenance of remission and safety following cessation of sirukumab treatment and to assess long-term corticosteroid use. Subjects will need to have follow-up safety evaluations for at least 16 weeks after receiving the last dose of study drug, applicable for those who have withdrawn prematurely from the study or who have completed Part A but are not eligible for Part B.

Sirukumab is a fully human anti interleukin (IL)-6 immunoglobulin G1-kappa monoclonal antibody (MAb) which is in development for the treatment of rheumatoid arthritis (RA). The continuing unmet need in subjects with asthma refractory to corticosteroid therapy and increased understanding of asthma pathogenesis have stimulated the development of targeted biologics based on predictive biomarkers. The majority of approaches to date have targeted T Helper 2 (Th2) cytokines or their downstream effects. Targeting IL-6 in severe asthma represents an unprecedented approach that has potential to address non-Th2 drivers of severe asthma. This multicenter, randomized, double-blind (sponsor-unblind), placebo-controlled, parallel group study will investigate the efficacy of sirukumab compared to placebo in subjects having uncontrolled severe asthma despite use of high dose inhaled corticosteroid (ICS) in combination with long-acting Beta-agonist (LABA). The study will employ a variable treatment period for individual subjects. Dosing will continue every 4 weeks until week 44 (inclusive), or until 24 weeks after the final subject has been randomized, whichever the sooner. Upon receiving the final dose of study medicine or placebo, subjects will enter a 16 week Follow Up period. Overall, the duration of participation for subjects who complete the full 44-week treatment period and Follow Up period may be up to 64 weeks. Approximately 175 subjects will be randomized such that 140 evaluable subjects complete the study.