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01.08.2011 | Research article | Ausgabe 4/2011 Open Access

Arthritis Research & Therapy 4/2011

A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee

Zeitschrift:
Arthritis Research & Therapy > Ausgabe 4/2011
Autoren:
Stanley B Cohen, Susanna Proudman, Alan J Kivitz, Francis X Burch, John P Donohue, Deborah Burstein, Yu-Nien Sun, Christopher Banfield, Michael S Vincent, Liyun Ni, Debra J Zack
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​ar3430) contains supplementary material, which is available to authorized users.

Competing interests

At the time the study was performed, SB Cohen was a consultant for Amgen Inc, Genentech, Biogen-IDEC, Merck, Sanofi-Aventis, Proctor and Gamble, Pfizer, Centocor, Scios, Bristol Meyers Squibb, and Wyeth-Ayerst; S Proudman was a consultant for Amgen Inc, Actelion, Pfizer, and Glaxo-Smith-Klein; A Kivitz, F Burch, and D Burstein were consultants for Amgen Inc; and J Donohue was a consultant for Amgen Inc, Genentech, and Bristol Myers Squibb. Y-N Sun, C Banfield, MS Vincent, L Ni, and DJ Zack are employees of Amgen Inc.

Authors' contributions

Y-N Sun, C Banfield, MS Vincent, L Ni, and DJ Zack made substantial contributions to the study concept or design. SB Cohen, S Proudman, AJ Kivitz, FX Burch, JP Donohue, and D Burstein assisted with the acquisition of the data. Y-N Sun and L Ni performed data analysis. All authors assisted with interpretation of the data, helped to draft and revise the manuscript for intellectual content, and approved the final manuscript before submission to the journal.

Abstract

Introduction

AMG 108 is a fully human, immunoglobulin subclass G2 (IgG2) monoclonal antibody that binds the human interleukin-1 (IL-1) receptor type 1, inhibiting the activity of IL-1a and IL-1b. In preclinical studies, IL-1 inhibition was shown to be beneficial in models of osteoarthritis (OA). The purpose of this two-part study was to evaluate the safety and pharmacokinetics (PK; Part A) and clinical effect (Part B) of AMG 108 in a double-blind, placebo-controlled, multiple-dose study in patients with OA of the knee.

Methods

In Part A, patients received placebo or AMG 108 subcutaneously (SC; 75 mg or 300 mg) or intravenously (IV; 100 mg or 300 mg) once every 4 weeks for 12 weeks; in Part B, patients received placebo or 300 mg AMG 108 SC, once every 4 weeks for 12 weeks. The clinical effect of AMG 108 was measured in Part B by using the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index pain score.

Results

In Part A, 68 patients were randomized, and 64 received investigational product. In Part B, 160 patients were randomized, and 159 received investigational product. AMG 108 was well tolerated. Most adverse events (AEs), infectious AEs, serious AEs and infections, as well as withdrawals from the study due to AEs occurred at similar rates in both active and placebo groups. One death was reported in an 80-year-old patient (Part A, 300 mg IV AMG 108; due to complications of lobar pneumonia). AMG 108 serum concentration-time profiles exhibited nonlinear PK. The AMG 108 group in Part B had statistically insignificant but numerically greater improvement in pain compared with the placebo group, as shown by the WOMAC pain scores (median change, -63.0 versus -37.0, respectively).

Conclusions

The safety profile of AMG 108 SC and IV was comparable with placebo in patients with OA of the knee. Patients who received AMG 108 showed statistically insignificant but numerically greater improvements in pain; however, minimal, if any, clinical benefit was observed.

Trial Registration

This study is registered with ClinicalTrials.gov with the identifier NCT00110942.
Zusatzmaterial
Additional file 1: dGEMRIC imaging, analysis and results. (DOC 401 KB)
13075_2010_3223_MOESM1_ESM.DOC
Authors’ original file for figure 1
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Authors’ original file for figure 2
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Authors’ original file for figure 3
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Authors’ original file for figure 4
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Authors’ original file for figure 5
13075_2010_3223_MOESM6_ESM.doc
Literatur
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