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Intranasal administration of recombinant human cartilage glycoprotein-39 as a treatment for rheumatoid arthritis: a phase II, multicentre, double-blind, randomised, placebo-controlled, parallel-group, dose-finding trial
  1. Robert B M Landewé1,
  2. Jos G A Houbiers2,
  3. Filip Van den Bosch3,
  4. Joanna in't Hout2,
  5. Patrick C P M Verschueren4,
  6. Jan H Meijerink2,
  7. Frank H J van den Hoogen5,
  8. Bedrich A Masek6,
  9. George A W Bruyn7,
  10. Jacques M G W Wouters8,
  11. Alexandre E Voskuyl9,
  12. Jacob M van Laar10,
  13. Johannes J W Bijlsma11,
  14. Désirée M F M van der Heijde1,
  15. Ferdinand C Breedveld10,
  16. Leo B A van de Putte12,
  17. André M M Miltenburg2,13,
  18. Filip de Keyser3
  1. 1Department of Rheumatology, University Hospital Maastricht, Maastricht, The Netherlands
  2. 2Clinical Development Department, Biometrics Department, Global Strategy Department and Pharmacology Department, NV Organon (Schering-Plough), Oss, The Netherlands
  3. 3Department of Rheumatology, University Hospital Gent, Gent, Belgium
  4. 4Department of Rheumatology, University Hospitals Leuven (Gasthuisberg), Leuven, Belgium
  5. 5Rheumatology, Sint Maartens Clinic, Nijmegen, The Netherlands
  6. 6Department of Rheumatology, VieCuri Medical Centre Noord-Limburg, Venlo, The Netherlands
  7. 7Department of Rheumatology, Medical Centre Leeuwarden South, Leeuwarden, The Netherlands
  8. 8Department of Rheumatology, St Franciscus Hospital, Rotterdam, The Netherlands
  9. 9Department of Rheumatology, VU University Medical Centre, Amsterdam, the Netherlands
  10. 10Department of Rheumatology, Leiden University Medical Centre, Leiden, the Netherlands
  11. 11Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands
  12. 12Department of Rheumatic Diseases, University Medical Centre Nijmegen, Nijmegen, The Netherlands
  13. 13NV Organon (Schering-Plough), Oss, The Netherlands
  1. Correspondence to Dr A M M Miltenburg, NV Organon (Schering-Plough), Molenstraat 110, 5342 CC Oss, The Netherlands; a.miltenburg{at}spcorp.com

Abstract

Background Autoantigen-specific immunotherapy by mucosal tolerance induction via the intranasal route is an attractive therapeutic option for the treatment of autoimmune diseases, including rheumatoid arthritis (RA). Human cartilage glycoprotein-39 (HC gp-39) has been identified as a potential key autoantigen in RA. Based on animal studies, intranasal administration of the autoantigen is hypothesised to induce immunological tolerance in patients with RA and to ameliorate disease activity. In a phase I/IIA clinical trial in patients with RA, intranasal application of HC gp-39 was safe and well tolerated.

Objective To investigate the efficacy of intranasally administered fully human, recombinant HC gp-39 (Org 39141) by a large clinical study.

Methods In a 13-week multicentre, double-blind, randomised, placebo-controlled, parallel-group, dose-finding, proof-of-concept trial, patients with RA (disease-modifying antirheumatic drug (DMARD) naive or after washout of DMARD treatment) were randomised to receive either intranasal applications of placebo or HC gp-39 in doses of 30, 150, 300 or 600 µg, once a week. The primary efficacy variable was the 28 joint count Disease Activity Score (DAS28).

Results During the treatment period the DAS28 decreased similarly for all treatment groups—including placebo—indicating lack of efficacy of intranasal HC gp-39 treatment in the current setting. Safety variables were similar for all study groups.

Conclusion It was concluded that with the treatment protocol used (dose levels and frequency of dosing), intranasal treatment with Org 39141 was safe but did not result in more clinical improvement than in placebo-treated patients.

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Footnotes

  • Competing interests JGAH, AMMM, JitH and JHM are or were employees of —at that time—NV Organon, Oss, the Netherlands. NV Organon—now Schering-Plough—sponsored this clinical trial. The other authors declare that they have no competing interests.

  • Ethics approval The protocol and informed consent form were approved by the institutional ethics committees of the 16 participating rheumatology hospitals.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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