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SAT0147 Safety and Efficacy of BI 655064, An Antagonistic Anti-CD40 Antibody in Rheumatoid Arthritis (RA) Patients
  1. S. Daniluk1,
  2. R. Ptaszynski2,
  3. U. Mueller-Ladner3,
  4. A. Petrikova4,
  5. H. Kellner5,
  6. E. Dokoupilova6,
  7. B. Kwiatkowska7,
  8. R. Alten8,
  9. C. Schwabe9,
  10. B. Rosenstock10,
  11. T. Doan11,
  12. R. Thiedmann10,
  13. F. Fleischer10,
  14. J. Hilbert12,
  15. S. Visvanathan12,
  16. S. Padula13,
  17. J. Steffgen10
  1. 1ClinicMed Badurski and Partners, Bialystok
  2. 2Rheumatica, Warsaw, Poland
  3. 3Giessen University, Kerckhoff-Klinik, Bad-Nauheim, Germany
  4. 4CTCenter MaVe, Olomouc, Czech Republic
  5. 5Centre for Inflammatory Joint Diseases, Munich, Germany
  6. 6Medical Plus, Uherske Hradiste, Czech Republic
  7. 7Prof. Eleonora Reicher Memorial National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland
  8. 8Schlossparkklinik, Berlin, Germany
  9. 9Auckland Clinical Studies, Auckland, New Zealand
  10. 10Medicine, Boehringer Ingelheim, Biberach, Germany
  11. 11Clinical, Boehringer Ingelheim, Sydney, Australia
  12. 12Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim, Ridgefield, United States
  13. 13Medicine, Boehringer Ingelheim, Ingelheim, Germany

Abstract

Background Blocking the CD40-CD40L pathway may be a new emergent treatment for patients with RA. BI 655064 is a humanized, purely antagonistic anti-CD40 monoclonal antibody. In healthy volunteers, BI 655064 was well tolerated in doses up to 240 mg q1w s.c. for 4 weeks. Doses ≥120 mg resulted in persistent >90% CD40 receptor occupancy and >90% inhibition of CD40L-induced CD54 upregulation.

Objectives BI 655064 was investigated in RA patients with prior inadequate response (IR) to a stable dose of MTX at ≥15 mg.

Methods In this double-blind, randomized trial, RA patients (n=67) were treated with either 120 mg BI 655064 or placebo q1w (2:1, respectively) for 12 weeks as add-on to MTX. Patients were stratified based on region (Eastern Europe vs. Western Europe/New Zealand). Inclusion criteria were ≥6 swollen and ≥6 tender joints, CRP ≥8 mg/L or ESR ≥28 mm/1h. The primary efficacy endpoint was ACR20 response at week 12.

Results Baseline variables of the 2 groups were comparable except mean baseline CRP, which was substantially lower in patients treated with BI 655064 (9.8 mg/L) vs. placebo (23.6 mg/L). Treatment was prematurely discontinued by 4 patients (9.1%) in the BI 655064 group and 4 (17.4%) in the placebo group. Adverse events (AE) were reported in 65.9% of BI 655064-treated patients vs. 78.3% of placebo-treated patients. Two SAEs were reported in each group, neither was considered drug-related. The most frequently reported AEs were nasopharyngitis (BI 655064: 13.6%, placebo: 21.7%) and headache (BI 655064: 6.8%, placebo: 13.0%). There were no relevant changes in safety-related laboratory parameters. Efficacy results of all patients (FAS), including a subgroup of patients with CRP > median (7.5 mg/L; upper limit of normal: 6.0 mg/L), are listed in the table.

Table 1

All 6 patients who had previously received anti-TNF therapy were in the BI 655064 group; 4 achieved an ACR20 and 2 achieved an ACR50 response. There was a median decrease in ESR and total rheumatoid factor in the BI 655064-treated group by 16 mm/h and 81.5 IU/mL, respectively, compared with a decrease of 9 mm/h and 0.2 IU/mL in the placebo group.

Conclusions In this relatively small proof-of-clinical-concept trial, treatment of MTX IR RA patients with BI 655064 did not indicate a relevant safety concern and showed moderate efficacy, which might have been impacted by the relatively high placebo response rate and the imbalance in baseline CRP.

Disclosure of Interest S. Daniluk: None declared, R. Ptaszynski: None declared, U. Mueller-Ladner Consultant for: Boehringer Ingelheim, A. Petrikova: None declared, H. Kellner: None declared, E. Dokoupilova: None declared, B. Kwiatkowska: None declared, R. Alten Grant/research support from: Boehringer Ingelheim, C. Schwabe Grant/research support from: Boehringer Ingelheim, B. Rosenstock Employee of: Boehringer Ingelheim, T. Doan Employee of: Boehringer Ingelheim, R. Thiedmann Employee of: Boehringer Ingelheim, F. Fleischer Employee of: Boehringer Ingelheim, J. Hilbert Employee of: Boehringer Ingelheim, S. Visvanathan Employee of: Boehringer Ingelheim, S. Padula Employee of: Boehringer Ingelheim, J. Steffgen Employee of: Boehringer-Ingelheim

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