Philip J Mease1,2, Slawomir Jeka3,4, Juan Jose Jaller3,4, Tasanee Kitumnuaypong3,4, Worawit Louthrenoo3,4, Herman Mann3,4, Galina Matsievskaia3,4, Enrique R Soriano3,4, Bin Jia3,4, Caihong Wang3,4, Jing Nie3,4, Elizabeth Hsia3,4. 1. From the Swedish Medical Center and University of Washington, Seattle, Washington; Janssen Research and Development LLC, Spring House, Pennsylvania, USA; Department of Rheumatology and Connective Tissue Diseases, 2nd University Hospital, CM UMK, Bydgoszcz, Poland; Centro de Reumatologia y Ortopedia, Universidad Metropolitana, Barranquilla, Colombia; Rajavithi Hospital, Bangkok, Thailand; Division of Rheumatology, Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand; Institute of Rheumatology, Prague, Czech Republic; Clinical Rheumatology Hospital #25, St. Petersburg, Russia; Head Rheumatology Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Janssen (China) Research and Development Center, Beijing, China. pmease@philipmease.com. 2. P.J. Mease, MD, Swedish Medical Center and University of Washington; S. Jeka, Professor, MD, Department of Rheumatology and Connective Tissue Diseases, 2nd University Hospital, CM UMK; J.J. Jaller, MD, Scientific Director, Centro de Reumatologia y Ortopedia, Docente Investigador, Universidad Metropolitana; T. Kitumnuaypong, MD, Rajavithi Hospital; W. Louthrenoo, MD, Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University; H. Mann, MD, Institute of Rheumatology; G. Matsievskaia, MD, Chief of Rheumatology Department, Clinical Rheumatology Hospital #25; E.R. Soriano, MD, MSc, Head Rheumatology Unit, Hospital Italiano de Buenos Aires; B. Jia, PhD, Janssen (China) Research and Development Center; C. Wang, MD, Immunology Therapeutic Area Head, Janssen (China) Research and Development Center; J. Nie, PhD, Senior Manager, Clinical Pharmacology, Janssen (China) Research and Development Center; E. Hsia, MD, MSCE, Janssen Research and Development LLC. pmease@philipmease.com. 3. From the Swedish Medical Center and University of Washington, Seattle, Washington; Janssen Research and Development LLC, Spring House, Pennsylvania, USA; Department of Rheumatology and Connective Tissue Diseases, 2nd University Hospital, CM UMK, Bydgoszcz, Poland; Centro de Reumatologia y Ortopedia, Universidad Metropolitana, Barranquilla, Colombia; Rajavithi Hospital, Bangkok, Thailand; Division of Rheumatology, Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand; Institute of Rheumatology, Prague, Czech Republic; Clinical Rheumatology Hospital #25, St. Petersburg, Russia; Head Rheumatology Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Janssen (China) Research and Development Center, Beijing, China. 4. P.J. Mease, MD, Swedish Medical Center and University of Washington; S. Jeka, Professor, MD, Department of Rheumatology and Connective Tissue Diseases, 2nd University Hospital, CM UMK; J.J. Jaller, MD, Scientific Director, Centro de Reumatologia y Ortopedia, Docente Investigador, Universidad Metropolitana; T. Kitumnuaypong, MD, Rajavithi Hospital; W. Louthrenoo, MD, Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University; H. Mann, MD, Institute of Rheumatology; G. Matsievskaia, MD, Chief of Rheumatology Department, Clinical Rheumatology Hospital #25; E.R. Soriano, MD, MSc, Head Rheumatology Unit, Hospital Italiano de Buenos Aires; B. Jia, PhD, Janssen (China) Research and Development Center; C. Wang, MD, Immunology Therapeutic Area Head, Janssen (China) Research and Development Center; J. Nie, PhD, Senior Manager, Clinical Pharmacology, Janssen (China) Research and Development Center; E. Hsia, MD, MSCE, Janssen Research and Development LLC.
Abstract
OBJECTIVE: To evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of CNTO6785, a fully human monoclonal antibody that binds to human interleukin 17A, in patients with active rheumatoid arthritis (RA) with inadequate response tomethotrexate (MTX) therapy. METHODS: This randomized, double-blind, placebo-controlled, dose-ranging study enrolled patients aged 18 to 80 years (inclusive) with active RA (≥ 6/66 swollen and ≥ 6/68 tender joints) who were refractory to MTX treatment (7.5-25 mg weekly, inclusive). The study duration was 38 weeks, containing a 10-week safety followup. Patients were randomized 1:1:1:1:1 to receive CNTO6785 15, 50, 100, or 200 mg every 4 weeks + MTX or placebo + MTX. The primary endpoint was American College of Rheumatology 20 (ACR20) response at Week 16. RESULTS: There were no significant differences from placebo in the proportion of patients treated with CNTO6785 in the primary endpoint of ACR20 response at Week 16. There were no significant findings in any additional efficacy variables through Week 32. No dose-response relationships or specific patterns were observed in adverse event profiles among CNTO6785 treatment groups. Infections occurred with similar frequency across all groups, and injection site reactions were mild or moderate and did not demonstrate a dose-response relationship. Median serum CNTO6785 concentration increases through Week 38 were about dose-proportional; the incidence of neutralizing antidrug antibodies was 19.4% and was not associated with study drug dose level. CONCLUSION:CNTO6785 was well tolerated, but did not demonstrate clinical efficacy in patients with active RA with inadequate response to MTX.
RCT Entities:
OBJECTIVE: To evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of CNTO6785, a fully human monoclonal antibody that binds to humaninterleukin 17A, in patients with active rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX) therapy. METHODS: This randomized, double-blind, placebo-controlled, dose-ranging study enrolled patients aged 18 to 80 years (inclusive) with active RA (≥ 6/66 swollen and ≥ 6/68 tender joints) who were refractory to MTX treatment (7.5-25 mg weekly, inclusive). The study duration was 38 weeks, containing a 10-week safety followup. Patients were randomized 1:1:1:1:1 to receive CNTO6785 15, 50, 100, or 200 mg every 4 weeks + MTX or placebo + MTX. The primary endpoint was American College of Rheumatology 20 (ACR20) response at Week 16. RESULTS: There were no significant differences from placebo in the proportion of patients treated with CNTO6785 in the primary endpoint of ACR20 response at Week 16. There were no significant findings in any additional efficacy variables through Week 32. No dose-response relationships or specific patterns were observed in adverse event profiles among CNTO6785 treatment groups. Infections occurred with similar frequency across all groups, and injection site reactions were mild or moderate and did not demonstrate a dose-response relationship. Median serum CNTO6785 concentration increases through Week 38 were about dose-proportional; the incidence of neutralizing antidrug antibodies was 19.4% and was not associated with study drug dose level. CONCLUSION: CNTO6785 was well tolerated, but did not demonstrate clinical efficacy in patients with active RA with inadequate response to MTX.
Authors: Andreas Kerschbaumer; Alexandre Sepriano; Josef S Smolen; Désirée van der Heijde; Maxime Dougados; Ronald van Vollenhoven; Iain B McInnes; Johannes W J Bijlsma; Gerd R Burmester; Maarten de Wit; Louise Falzon; Robert Landewé Journal: Ann Rheum Dis Date: 2020-02-07 Impact factor: 19.103
Authors: Mohamed A Alfaleh; Hashem O Alsaab; Ahmad Bakur Mahmoud; Almohanad A Alkayyal; Martina L Jones; Stephen M Mahler; Anwar M Hashem Journal: Front Immunol Date: 2020-08-28 Impact factor: 7.561