Article Text

PDF
THU0100 Results from a 2-part, proof-of-concept, dose-ranging, randomized, double-blind, placebo-controlled, phase 2 study of sirukumab, a human anti-IL-6 monoclonal antibody, in patients with active rheumatoid arthritis despite methotrexate therapy
  1. B. Hsu1,
  2. S. Sheng1,
  3. J.S. Smolen2,
  4. M.E. Weinblatt3
  1. 1Janssen R&D, Spring House, PA, United States
  2. 2Med U Vienna & Hietzing Hosp, Vienna, Austria
  3. 3Brigham & Women’s Hosp, Boston, MA, United States

Abstract

Objectives To determine the efficacy and safety of SC sirukumab (SRM) dose regimens & to describe PK & PD in active RA pts in a Ph2 dose-ranging Part B study.

Methods Pts w/ active RA despite MTX were randomized: (1) PBO q2w at wks 0–10, then SRM 100mg q2w at wks 12–24; (2) SRM 100mg q2w at wks 0–24; (3) SRM 100mg q4w at wks 0–24; (4) SRM 50mg q4w at wks 0–24; or (5) SRM 25mg q4w at wks 0–24. Primary endpt ACR50 at wk12, compared btw each active grp vs PBO. Key secondary endpts: change from baseline (BL) in DAS28 (CRP) at wk12, serum SRM PK, & % change from BL in serum CRP at wk2.

Results In Part B, 151 pts were randomized & treated. 85% female, 60% Caucasian, 21% Japanese. At BL, mean age:53±11yrs, mean weight:69±15kg, mean DAS28 (CRP):5.9±0.9, & median serum CRP:1.7mg/dL. 26 (87%) PBO pts crossed over to SRM 100mg q2w at wk12. At wk12, SRM sig improved ACR50 (overall p=0.010) & sig decreased DAS28 (p<0.001). At wk12, higher % of pts achieved moderate/good DAS28 (CRP) responses in each grp (93.4%, 86.6%, 90.0%, & 83.9% in SRM 100mg q2w, 100mg q4w, 50mg q4w, & 25mg q4w grps, resp) compared w/ PBO (60.0%). Stat sig (p<0.05) was achieved in SRM 100mg q2w & 50mg q4w tx grps. SRM PK were linear over SC dose range of 25–100mg. PK were generally consistent btw Caucasians & Japanese. Mean serum CRP decreased>80% from BL w/ SRM at wk2 & remained suppressed thru wk24. Thru wk38, AEs occurred more often w/ SRM than PBO (81 vs 67%), including minor infections/infestations (31 vs 13%), GI disorders (19 vs 10%), & injection site reactions (16 vs 3%). Leukopenia (19, 13% [1 NCI Gr 3]), neutropenia (5, 3% [3 Gr 3]), thrombocytopenia (3, 2% [1 Gr 3, 1 Gr 4]), & lymphopenia (2, 1%, [1 Gr 3, 1 Gr 4]) were reported w/ SRM. ALT (8 Gr 3, 7%) & AST (1 Gr 3, 1%) elevations not associated w/ increased bilirubin; & sustained increase from BL starting at wk2 in total cholesterol (mean SRM vs PBO: 19%±17% vs -5%±12%) & LDL (20%±20% vs -4%±22%) were seen w/ SRM. These lab abnormalities occurred w/o dose relationship or short term clinical sequelae. SAEs were more common w/ PBO (4, 13%) than SRM (13, 9%); majority were infections. 1 pt died of unrelated brain aneurysm. 4/136 (3%; 2 100mg q4w, 2 PBO→100mg q2w) evaluable pts had antibodies to SRM thru wk38; 3 of these pts were ACR50 responders at wk24, 0 had injection site reactions.

Conclusions SRM was efficacious & generally well tolerated. SRM PK were linear over SC regimens ranging from 25 to 100mg.

Disclosure of Interest B. Hsu Employee of: Janssen Research & Development, LLC, S. Sheng Employee of: Janssen Research & Development, LLC, J. Smolen Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study, M. Weinblatt Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.