A Multicentre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Sirukumab in the Treatment of Giant Cell Arteritis

Abstract

Introduction: To evaluate the efficacy and safety of sirukumab in giant cell arteritis (GCA).

Methods: In this multicentre, randomised, double-blind, placebo-controlled, two-part phase 3 trial (NCT02531633; Part A [52-week double-blind treatment]; Part B [104-week follow-up]), patients with GCA were randomised (3:3:2:2:2) to sirukumab 100 mg every 2 weeks plus 6-month or 3-month prednisone taper, sirukumab 50 mg every 4 weeks plus 6-month prednisone taper, or placebo every 2 weeks plus 6-month or 12-month prednisone taper. The primary endpoint was the proportion of patients in sustained remission at week 52. Secondary endpoints included disease flare and safety. The study was terminated early (October 2017; sponsor decision).

Results: Of 161 patients randomised (sirukumab: n = 107; placebo: n = 54), 28 (17.4%) completed week 52 (median treatment duration: 24-30 weeks). In a revised intent-to-treat (ITT) subgroup (completed week 52 or discontinued before study termination [n = 55]); six patients (all receiving sirukumab) achieved the primary endpoint. In the ITT population (n = 161), the proportion of patients with flares (week 2-52) was lower with sirukumab (18.4-30.8%) than placebo (37.0-40.0%). The proportion of patients with flares (week 2-12) was highest with sirukumab 100 mg every 2 weeks plus 3-month prednisone taper (23.1%). In Part A, 94.4% of patients reported ≥ 1 treatment-emergent adverse event (TEAE); 19.3% reported serious TEAEs. The proportions of patients with TEAEs were generally similar across treatment arms. No deaths occurred.

Conclusions: Although data were limited due to early termination and shortened treatment duration, sirukumab treatment resulted in numerically lower proportions of patients with flare by week 52 versus placebo, with no unexpected safety findings.

Trial registration: Clinicaltrials.gov: NCT02531633.

Keywords: Clinical trial; Corticosteroid taper; Giant cell arteritis; Interleukin-6; Sirukumab.

Figures

Fig. 1

Study design (as originally planned). aRescue glucocorticoid permitted without the requirement to withdraw. bOptional (investigator discretion). q2w every 2 weeks, q4w every 4 weeks

Fig. 2

Patient disposition. aApplies to patients who withdrew early from the study or who attended with week 52 visit of Part A and did not enter Part B. bViolation of inclusion/exclusion criteria. cOther: sponsor request. dPatients who received ≥ 1 dose SC sirukumab/placebo. ePatients who received ≥ 1 dose of SC sirukumab/placebo and completed 52 weeks (n = 28) or discontinued prior to study termination (n = 27). All patients who were randomised received their allocated treatment. A total of 26 patients continued to Part B; 8/26 received ≥ 1 dose of open-label sirukumab. No patients completed the 104-week extension phase; this was due to early withdrawal or study termination (25 patients withdrawn at sponsor request; one lost to follow-up). ITT intent-to-treat, q2w every 2 weeks, q4w every 4 weeks, SC subcutaneous

Fig. 3

Change in inflammatory markers from baseline to week 52: a C-reactive protein and b erythrocyte sedimentation rate (safety population). q2w every 2 weeks, q4w every 4 weeks, SC subcutaneous