PMID- 27489241
OWN - NLM
STAT- MEDLINE
DCOM- 20171020
LR  - 20180223
IS  - 1468-3288 (Electronic)
IS  - 0017-5749 (Linking)
VI  - 66
IP  - 11
DP  - 2017 Nov
TI  - Anti-NKG2D monoclonal antibody (NNC0142-0002) in active Crohn's disease: a 
      randomised controlled trial.
PG  - 1918-1925
LID - 10.1136/gutjnl-2016-311824 [doi]
AB  - OBJECTIVE: Anti-NKG2D (NNC0142-0002) is an antagonising human immunoglobulin G4 
      monoclonal antibody that binds to natural killer group 2 member D (NKG2D) 
      receptors, which are expressed by T cells and innate lymphoid cells, and may be 
      linked to mucosal damage in Crohn's disease (CD). DESIGN: Seventy-eight patients 
      (aged >/=18 and </=75 years) with CD for >/=3 months, Crohn's Disease Activity Index 
      (CDAI) >/=220 and </=450 and either C-reactive protein >/=10 mg/L or endoscopic 
      evidence of inflammation, were randomised 1:1 to a single subcutaneous (SC) dose 
      of 2 mg/kg anti-NKG2D or placebo. Primary endpoint was change in CDAI (DeltaCDAI) 
      from baseline to week 4. Prespecified significance level was 10% for CDAI 
      endpoints. A futility analysis was instituted due to slow recruitment. RESULTS: 
      Primary endpoint was not significantly different between anti-NKG2D and placebo 
      (week 4 DeltaCDAI=-16); however, there was a significant difference by week 12 
      (DeltaCDAI=-55; p</=0.10). Significant improvements were noted in the non-failure to 
      biologics subgroup (treated with anti-NKG2D (n=28)) from week 1 onward. Greater 
      effects of anti-NKG2D were also observed in patients with baseline CDAI >/=330. 
      Frequencies of adverse events (AEs) were comparable between anti-NKG2D and 
      placebo. Most AEs were mild (49%) or moderate (43%). No antidrug antibodies were 
      observed. CONCLUSIONS: A single SC dose of 2 mg/kg anti-NKG2D did not reduce 
      disease activity at week 4 versus placebo, but the difference was significant at 
      week 12, and effects were evident in key subgroups. These data support further 
      development of anti-NKG2D in IBD. TRIAL REGISTRATION NUMBER: NCT01203631.
CI  - Published by the BMJ Publishing Group Limited. For permission to use (where not 
      already granted under a licence) please go to 
      http://www.bmj.com/company/products-services/rights-and-licensing/.
FAU - Allez, Matthieu
AU  - Allez M
AD  - Department of Gastroenterology, APHP, Hopital Saint Louis, INSERM UMRS 1160, 
      Paris Diderot, Sorbonne Paris-Cite University, Paris, France.
FAU - Skolnick, Brett E
AU  - Skolnick BE
AD  - Novo Nordisk, Inc., Princeton, New Jersey, USA.
FAU - Wisniewska-Jarosinska, Maria
AU  - Wisniewska-Jarosinska M
AD  - Department of Gastroenterology, Medical University of Lodz, Lodz, Poland.
FAU - Petryka, Robert
AU  - Petryka R
AD  - NZOZ Vivamed, Warsaw, Poland.
FAU - Overgaard, Rune Viig
AU  - Overgaard RV
AD  - Novo Nordisk A/S, Soborg, Denmark.
LA  - eng
SI  - ClinicalTrials.gov/NCT01203631
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20160803
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (KLRK1 protein, human)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily K)
RN  - 0 (NNC0142-0002 monoclonal antibody)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Crohn Disease/*drug therapy/immunology
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Immunoglobulin G/*therapeutic use
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - NK Cell Lectin-Like Receptor Subfamily K/*immunology
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - CROHN'S DISEASE
EDAT- 2016/08/05 06:00
MHDA- 2017/10/21 06:00
CRDT- 2016/08/05 06:00
PHST- 2016/03/09 00:00 [received]
PHST- 2016/06/30 00:00 [revised]
PHST- 2016/07/14 00:00 [accepted]
PHST- 2016/08/05 06:00 [pubmed]
PHST- 2017/10/21 06:00 [medline]
PHST- 2016/08/05 06:00 [entrez]
AID - gutjnl-2016-311824 [pii]
AID - 10.1136/gutjnl-2016-311824 [doi]
PST - ppublish
SO  - Gut. 2017 Nov;66(11):1918-1925. doi: 10.1136/gutjnl-2016-311824. Epub 2016 Aug 3.