PMID- 21801403
OWN - NLM
STAT- MEDLINE
DCOM- 20120329
LR  - 20220311
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 13
IP  - 4
DP  - 2011 Jul 29
TI  - A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to 
      IL-1R1) in patients with osteoarthritis of the knee.
PG  - R125
LID - 10.1186/ar3430 [doi]
AB  - 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.
FAU - Cohen, Stanley B
AU  - Cohen SB
AD  - Rheumatology, Metroplex Clinical Research Center, 8144 Walnut Hill Lane, Dallas, 
      TX 75231, USA. Arthdoc@aol.com
FAU - Proudman, Susanna
AU  - Proudman S
FAU - Kivitz, Alan J
AU  - Kivitz AJ
FAU - Burch, Francis X
AU  - Burch FX
FAU - Donohue, John P
AU  - Donohue JP
FAU - Burstein, Deborah
AU  - Burstein D
FAU - Sun, Yu-Nien
AU  - Sun YN
FAU - Banfield, Christopher
AU  - Banfield C
FAU - Vincent, Michael S
AU  - Vincent MS
FAU - Ni, Liyun
AU  - Ni L
FAU - Zack, Debra J
AU  - Zack DJ
LA  - eng
SI  - ClinicalTrials.gov/NCT00110942
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20110729
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (AMG 108)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Receptors, Interleukin-1)
SB  - IM
MH  - Antibodies, Monoclonal/*administration & dosage/*pharmacokinetics
MH  - Antirheumatic Agents/*administration & dosage/*pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Osteoarthritis, Knee/*drug therapy
MH  - Pain/drug therapy
MH  - Receptors, Interleukin-1/antagonists & inhibitors
PMC - PMC3239365
EDAT- 2011/08/02 06:00
MHDA- 2012/03/30 06:00
PMCR- 2011/07/29
CRDT- 2011/08/02 06:00
PHST- 2010/10/01 00:00 [received]
PHST- 2011/01/06 00:00 [revised]
PHST- 2011/07/29 00:00 [accepted]
PHST- 2011/08/02 06:00 [entrez]
PHST- 2011/08/02 06:00 [pubmed]
PHST- 2012/03/30 06:00 [medline]
PHST- 2011/07/29 00:00 [pmc-release]
AID - ar3430 [pii]
AID - 10.1186/ar3430 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2011 Jul 29;13(4):R125. doi: 10.1186/ar3430.