Toreforant, A Histamine H4 Receptor Antagonist, in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: Results of 2 Phase II Studies

Affiliations

¹ From the Immunology department, Janssen Research & Development, LLC, San Diego, California; the Medical Affairs department, Janssen Research & Development, LLC, Horsham, Pennsylvania; the Biostatistics department and the Immunology department, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA; Early Development, Janssen China Research and Development, Shanghai, China; the Biostatistics department, Janssen Research & Development, LLC, Belmont, Massachusetts, USA; Rheumatology Department, M&M Centers LTD., Adazi, Latvia; Immunology Department, University of Rochester, Rochester, New York, USA; Internal Medicine, University of Occupational and Environmental Health, Kitakyushu; Rheumatology, Keio University Hospital, Tokyo, Japan; Rheumatology, Medical University of Vienna and Hietzing Hospital, Vienna, Austria.R.L. Thurmond, PhD, Immunology Department, Janssen Research & Development, LLC; A. Greenspan, MD, Medical Affairs Department, Janssen Research & Development, LLC; W. Radziszewski, MD, PhD, Immunology Department, Janssen Research & Development, LLC; X.L. Xu, PhD, Immunology Department, Janssen Research & Development, LLC; Y. Miao, MS, Biostatistics Department, Janssen Research & Development, LLC; B. Chen, PhD, Early Development, Janssen China Research and Development; T. Ge, PhD, Biostatistics Department, Janssen Research & Development, LLC; B. Zhou, PhD, Biostatistics, Janssen Research & Development, LLC; D.G. Baker, MD, Immunology Department, Janssen Research & Development, LLC; D. Pavlova, MD, Rheumatology, M&M Centers Ltd.; C.T. Ritchlin, MD, Immunology Department, University of Rochester; Y. Tanaka, MD, PhD, Internal Medicine, University of Occupational and Environmental Health; T. Takeuchi, MD, PhD, Rheumatology, Keio University Hospital; J.S. Smolen, MD, Rheumatology, Medical University of Vienna and Hietzing Hospital. RThurmon@its.jnj.com.
² From the Immunology department, Janssen Research & Development, LLC, San Diego, California; the Medical Affairs department, Janssen Research & Development, LLC, Horsham, Pennsylvania; the Biostatistics department and the Immunology department, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA; Early Development, Janssen China Research and Development, Shanghai, China; the Biostatistics department, Janssen Research & Development, LLC, Belmont, Massachusetts, USA; Rheumatology Department, M&M Centers LTD., Adazi, Latvia; Immunology Department, University of Rochester, Rochester, New York, USA; Internal Medicine, University of Occupational and Environmental Health, Kitakyushu; Rheumatology, Keio University Hospital, Tokyo, Japan; Rheumatology, Medical University of Vienna and Hietzing Hospital, Vienna, Austria.R.L. Thurmond, PhD, Immunology Department, Janssen Research & Development, LLC; A. Greenspan, MD, Medical Affairs Department, Janssen Research & Development, LLC; W. Radziszewski, MD, PhD, Immunology Department, Janssen Research & Development, LLC; X.L. Xu, PhD, Immunology Department, Janssen Research & Development, LLC; Y. Miao, MS, Biostatistics Department, Janssen Research & Development, LLC; B. Chen, PhD, Early Development, Janssen China Research and Development; T. Ge, PhD, Biostatistics Department, Janssen Research & Development, LLC; B. Zhou, PhD, Biostatistics, Janssen Research & Development, LLC; D.G. Baker, MD, Immunology Department, Janssen Research & Development, LLC; D. Pavlova, MD, Rheumatology, M&M Centers Ltd.; C.T. Ritchlin, MD, Immunology Department, University of Rochester; Y. Tanaka, MD, PhD, Internal Medicine, University of Occupational and Environmental Health; T. Takeuchi, MD, PhD, Rheumatology, Keio University Hospital; J.S. Smolen, MD, Rheumatology, Medical University of Vienna and Hietzing Hospital.

PMID: 27422891
DOI: 10.3899/jrheum.160164

Clinical Trial

Toreforant, A Histamine H4 Receptor Antagonist, in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: Results of 2 Phase II Studies

Robin L Thurmond et al. J Rheumatol. 2016 Sep.

. 2016 Sep;43(9):1637-42.

doi: 10.3899/jrheum.160164. Epub 2016 Jul 15.

Affiliations

¹ From the Immunology department, Janssen Research & Development, LLC, San Diego, California; the Medical Affairs department, Janssen Research & Development, LLC, Horsham, Pennsylvania; the Biostatistics department and the Immunology department, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA; Early Development, Janssen China Research and Development, Shanghai, China; the Biostatistics department, Janssen Research & Development, LLC, Belmont, Massachusetts, USA; Rheumatology Department, M&M Centers LTD., Adazi, Latvia; Immunology Department, University of Rochester, Rochester, New York, USA; Internal Medicine, University of Occupational and Environmental Health, Kitakyushu; Rheumatology, Keio University Hospital, Tokyo, Japan; Rheumatology, Medical University of Vienna and Hietzing Hospital, Vienna, Austria.R.L. Thurmond, PhD, Immunology Department, Janssen Research & Development, LLC; A. Greenspan, MD, Medical Affairs Department, Janssen Research & Development, LLC; W. Radziszewski, MD, PhD, Immunology Department, Janssen Research & Development, LLC; X.L. Xu, PhD, Immunology Department, Janssen Research & Development, LLC; Y. Miao, MS, Biostatistics Department, Janssen Research & Development, LLC; B. Chen, PhD, Early Development, Janssen China Research and Development; T. Ge, PhD, Biostatistics Department, Janssen Research & Development, LLC; B. Zhou, PhD, Biostatistics, Janssen Research & Development, LLC; D.G. Baker, MD, Immunology Department, Janssen Research & Development, LLC; D. Pavlova, MD, Rheumatology, M&M Centers Ltd.; C.T. Ritchlin, MD, Immunology Department, University of Rochester; Y. Tanaka, MD, PhD, Internal Medicine, University of Occupational and Environmental Health; T. Takeuchi, MD, PhD, Rheumatology, Keio University Hospital; J.S. Smolen, MD, Rheumatology, Medical University of Vienna and Hietzing Hospital. RThurmon@its.jnj.com.
² From the Immunology department, Janssen Research & Development, LLC, San Diego, California; the Medical Affairs department, Janssen Research & Development, LLC, Horsham, Pennsylvania; the Biostatistics department and the Immunology department, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA; Early Development, Janssen China Research and Development, Shanghai, China; the Biostatistics department, Janssen Research & Development, LLC, Belmont, Massachusetts, USA; Rheumatology Department, M&M Centers LTD., Adazi, Latvia; Immunology Department, University of Rochester, Rochester, New York, USA; Internal Medicine, University of Occupational and Environmental Health, Kitakyushu; Rheumatology, Keio University Hospital, Tokyo, Japan; Rheumatology, Medical University of Vienna and Hietzing Hospital, Vienna, Austria.R.L. Thurmond, PhD, Immunology Department, Janssen Research & Development, LLC; A. Greenspan, MD, Medical Affairs Department, Janssen Research & Development, LLC; W. Radziszewski, MD, PhD, Immunology Department, Janssen Research & Development, LLC; X.L. Xu, PhD, Immunology Department, Janssen Research & Development, LLC; Y. Miao, MS, Biostatistics Department, Janssen Research & Development, LLC; B. Chen, PhD, Early Development, Janssen China Research and Development; T. Ge, PhD, Biostatistics Department, Janssen Research & Development, LLC; B. Zhou, PhD, Biostatistics, Janssen Research & Development, LLC; D.G. Baker, MD, Immunology Department, Janssen Research & Development, LLC; D. Pavlova, MD, Rheumatology, M&M Centers Ltd.; C.T. Ritchlin, MD, Immunology Department, University of Rochester; Y. Tanaka, MD, PhD, Internal Medicine, University of Occupational and Environmental Health; T. Takeuchi, MD, PhD, Rheumatology, Keio University Hospital; J.S. Smolen, MD, Rheumatology, Medical University of Vienna and Hietzing Hospital.

PMID: 27422891
DOI: 10.3899/jrheum.160164

Abstract

Objective: To assess toreforant (selective histamine H4 receptor antagonist) in active rheumatoid arthritis (RA).

Methods: In a phase IIa, double-blind, placebo-controlled test, 86 patients were randomized (2:1) to once-daily toreforant 100 mg or placebo for 12 weeks. In phase IIb, double-blind, placebo-controlled, dose-range-finding evaluations, 272 patients were randomized (1:1:1:1) to once-daily placebo or toreforant 3/10/30 mg. Primary efficacy endpoints for both studies were Week 12 changes in 28-joint Disease Activity Score-C-reactive protein (DAS28-CRP).

Results: Phase IIa testing was terminated prematurely (patient fatality; secondary hemophagocytic lymphohistiocytosis). Posthoc analyses indicated toreforant 100 mg/day reduced RA signs/symptoms through Week 12. Phase IIb testing, however, showed no significant Week 12 improvement in DAS28-CRP with toreforant.

Conclusion: Toreforant was not effective in phase IIb testing.

Keywords: CLINICAL TRIAL; HISTAMINE H4 RECEPTOR ANTAGONIST; METHOTREXATE; RHEUMATOID ARTHRITIS.

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Toreforant, A Histamine H4 Receptor Antagonist, in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: Results of 2 Phase II Studies

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Toreforant, A Histamine H4 Receptor Antagonist, in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: Results of 2 Phase II Studies

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