FRI0292 A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF SIRUKUMAB IN THE TREATMENT OF PATIENTS WITH GIANT CELL ARTERITIS
Authors: Wolfgang Schmidt, Bhaskar Dasgupta, Raashid Luqmani, Sebastian Unizony, Zhihong Lai, Regina Kurrasch, Ivana Lazic, Kurt Brown, Ravi Rao
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Sirukumab (SIR), a selective, high-affinity human monoclonal antibody to the interleukin-6 (IL-6) cytokine, was under development for giant-cell arteritis (GCA) and other diseases. <h3>Objectives</h3> To evaluate the efficacy and safety of sirukumab (SIR) in subjects with GCA. <h3>Methods</h3> This 2-part phase 3 study enrolled subjects with active GCA (NCT02531633). Subjects were randomized in a 3:3:2:2:2 ratio to one of 5 treatment arms: SIR 100 mg SC q2w + 6-mo prednisone taper (SIR100+6mo), SIR 100 mg SC q2w + 3-mo prednisone taper (SIR100+3mo), SIR 50 mg SC q4w + 6-mo prednisone taper (SIR50+6mo), placebo (PBO) SC q2w + 6-mo prednisone taper (PBO+6mo), PBO SC q2w + 12-mo prednisone taper (PBO+12mo), for 52-week treatment(Part A). Following completion of Part A, subjects could enroll into the study extension with option for open label SIR treatment (Part B). The primary endpoint was the proportion of subjects in sustained remission at Week 52. Secondary endpoints included sustained remission over time, disease flare, and safety. As a result of the early study termination due to administrative reasons, the revised primary endpoint intent-to-treat analysis (revised ITT, N=55) included only subjects who received at least 1 dose of the SC investigational product and had completed 52 weeks (N=28) or had discontinued the study prior to study termination (n=27). <h3>Results</h3> A total of 161 of planned 204 subjects were randomized (mean age 69.6 years, 77.0% female, 98.1% white, 55.9% with new-onset disease). Baseline prednisone dose was ≥30 mg/day in 50.9% of subjects. The proportions of subjects with disease flares from Week 2 (N=155) to Week 52 were lower in the SIR100+6mo (18.4%), SIR 100+3mo (28.2%) and SIR50+6mo (30.8%) arms compared to the PBO+6mo (40%) and PBO+12mo (37%) arms. In Part A, 152 subjects (94.4%) experienced at least 1 treatment-emergent adverse event (TEAE), with similar proportions of subjects across the treatment arms. The most common TEAE's (&gt;10% total subjects) were headache, arthralgia, back pain, cough, upper respiratory tract infection. Treatment-emergent serious adverse events (TESAE) were reported for 31 subjects with similar incidence across all treatment arms. There were no reported deaths, GI perforations or TB activation. Infections and infestations were the most common TESAE, 6 subjects, with no clear difference between SIR and PBO. Two subjects had new onset GCA-related vision loss (SIR100+3mo, n=1; SIR50+6mo, n=1). There were 3 subjects with adjudicated major adverse cardiovascular events (SIR100+3mo, n=2; PBO+12mo, n=1). NCI CTCAE Grade 3 or 4 laboratory abnormalities of increased ALT, bilirubin, cholesterol, triglycerides and decreased leukocytes, neutrophils, and platelets occurred only in SIR treatment arms (0.6 to 2.5% of total subjects). <h3>Conclusion</h3> As a result of early study termination, only a few subjects, all in SIR treatment arms, achieved the primary endpoint of sustained remission at Week 52. The proportion of subjects with flares from Week 2 – 52 were higher in the PBO arms compared to SIR arms. The overall safety was consistent with the known SIR safety profile. Study funded by GSK <h3> Disclosure of Interests:</h3> Wolfgang Schmidt Grant/research support from: GSK, Roche, Novartis, Sanofi, Consultant for: GSK, Roche, Novartis, Sanofi, Bhaskar Dasgupta Consultant for: Roche, GSK, Sanofi, BMS, Abbvie, Speakers bureau: Roche, Raashid Luqmani Grant/research support from: Roche, Vifor and GSK, Sebastian Unizony Grant/research support from: F. Hoffmann-La Roche, Genentech, Consultant for: Kiniksa, Sanofi, GSK, Zhihong Lai Shareholder of: GSK, Employee of: GSK, Regina Kurrasch Shareholder of: GSK, Employee of: GSK, Ivana Lazic Shareholder of: GSK, Employee of: GSK, Kurt Brown Shareholder of: GSK, Employee of: GSK, Ravi Rao Shareholder of: GSK, Employee of: GSK