PMID- 29018537
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240327
IS  - 2053-8790 (Print)
IS  - 2053-8790 (Electronic)
IS  - 2053-8790 (Linking)
VI  - 4
IP  - 1
DP  - 2017
TI  - Safety, pharmacokinetics and pharmacodynamics of AMG 811, an anti-interferon-gamma 
      monoclonal antibody, in SLE subjects without or with lupus nephritis.
PG  - e000226
LID - 10.1136/lupus-2017-000226 [doi]
LID - e000226
AB  - OBJECTIVE: To evaluate safety, pharmacokinetics and pharmacodynamics of 
      anti-interferon (IFN)-gamma monoclonal antibody AMG 811 in subjects with SLE without 
      or with lupus nephritis (LN). METHODS: In this phase Ib, randomised, 
      multiple-dose escalation study (NCT00818948), subjects without LN were randomised 
      to subcutaneous AMG 811 (6, 20 or 60 mg) or placebo and subjects with LN were 
      randomised to subcutaneous AMG 811 (20, 60 or 120 mg) or placebo every four weeks 
      for three total doses. Outcomes included incidence of adverse events (AEs); 
      pharmacokinetics; levels of serum proteins (CXCL-10, interleukin 18, monocyte 
      chemotactic protein-1); changes in gene transcript profiles and clinical 
      parameters (Safety of Estrogen in Lupus Erythematosus National 
      Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) 
      scores, proteinuria, anti-double-stranded DNA (anti-dsDNA) antibodies, C3 
      complement, C4 complement). RESULTS: Fifty-six subjects enrolled (28 SLE without 
      LN; 28 with LN). Baseline mean SELENA-SLEDAI scores were 2.2 and 12.0 for SLE 
      subjects without and with LN, respectively. Most subjects reported an AE; no 
      meaningful imbalances were observed between AMG 811 and placebo. Pharmacokinetic 
      profiles were similar and mostly dose-proportional in subjects without or with 
      LN. AMG 811 treatment reduced CXCL-10 protein levels and blood-based RNA IFN-gamma 
      Blockade Signature compared with placebo. Reductions were less pronounced and not 
      sustained in subjects with LN, even at the highest dose tested, compared with 
      subjects without LN. No effect on SELENA-SLEDAI scores, proteinuria, C3 or C4 
      complement levels, or anti-dsDNA antibodies was observed. CONCLUSION: AMG 811 
      demonstrated favourable pharmacokinetics and acceptable safety profile but no 
      evidence of clinical impact. IFN-gamma-associated biomarkers decreased with AMG 811; 
      effects were less pronounced and not sustained in LN subjects. TRIAL REGISTRATION 
      NUMBER: NCT00818948; results.
FAU - Boedigheimer, Michael J
AU  - Boedigheimer MJ
AD  - Amgen Inc., Thousand Oaks, California, USA.
FAU - Martin, David A
AU  - Martin DA
AD  - Amgen Inc., Seattle, Washington, USA.
FAU - Amoura, Zahir
AU  - Amoura Z
AD  - French National Reference Center for SLE, Hopital Pitie-Salpetriere, Paris, 
      France.
FAU - Sanchez-Guerrero, Jorge
AU  - Sanchez-Guerrero J
AD  - Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, 
      Mexico.
FAU - Romero-Diaz, Juanita
AU  - Romero-Diaz J
AD  - Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, 
      Mexico.
FAU - Kivitz, Alan
AU  - Kivitz A
AD  - Altoona Center for Clinical Research, Duncansville, Pennsylvania, USA.
FAU - Aranow, Cynthia
AU  - Aranow C
AD  - Feinstein Institute for Medical Research, Manhasset, USA.
FAU - Chan, Tak Mao
AU  - Chan TM
AD  - Queen Mary Hospital, University of Hong Kong, Hong Kong.
FAU - Chong, Yip Boon
AU  - Chong YB
AD  - University Malaya Medical Centre, Kuala Lumpur, Malaysia.
FAU - Chiu, Kit
AU  - Chiu K
AD  - Amgen Inc., Thousand Oaks, California, USA.
FAU - Wang, Christine
AU  - Wang C
AD  - Amgen Inc., Thousand Oaks, California, USA.
FAU - Sohn, Winnie
AU  - Sohn W
AD  - Amgen Inc., Thousand Oaks, California, USA.
FAU - Arnold, Gregory E
AU  - Arnold GE
AD  - Amgen Inc., Thousand Oaks, California, USA.
FAU - Damore, Michael A
AU  - Damore MA
AD  - Amgen Inc., Thousand Oaks, California, USA.
FAU - Welcher, Andrew A
AU  - Welcher AA
AD  - Amgen Inc., Thousand Oaks, California, USA.
FAU - Sullivan, Barbara A
AU  - Sullivan BA
AD  - Amgen Inc., Thousand Oaks, California, USA.
FAU - Kotzin, Brian L
AU  - Kotzin BL
AD  - Amgen Inc., Thousand Oaks, California, USA.
FAU - Chung, James B
AU  - Chung JB
AD  - Amgen Inc., Thousand Oaks, California, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00818948
PT  - Journal Article
DEP - 20170914
PL  - England
TA  - Lupus Sci Med
JT  - Lupus science & medicine
JID - 101633705
PMC - PMC5604705
EDAT- 2017/10/12 06:00
MHDA- 2017/10/12 06:01
PMCR- 2017/09/14
CRDT- 2017/10/12 06:00
PHST- 2017/04/20 00:00 [received]
PHST- 2017/06/21 00:00 [revised]
PHST- 2017/06/24 00:00 [accepted]
PHST- 2017/10/12 06:00 [entrez]
PHST- 2017/10/12 06:00 [pubmed]
PHST- 2017/10/12 06:01 [medline]
PHST- 2017/09/14 00:00 [pmc-release]
AID - lupus-2017-000226 [pii]
AID - 10.1136/lupus-2017-000226 [doi]
PST - epublish
SO  - Lupus Sci Med. 2017 Sep 14;4(1):e000226. doi: 10.1136/lupus-2017-000226. 
      eCollection 2017.