title: Anti-NKG2D monoclonal antibody (NNC0142-0002) in active Crohn's disease: a randomised controlled trial.
abstract: 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).
  
  
  
  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 (ΔCDAI) from baseline to week 4. Prespecified significance level was 10% for CDAI endpoints. A futility analysis was instituted due to slow recruitment.
  
  
  
  Primary endpoint was not significantly different between anti-NKG2D and placebo (week 4 ΔCDAI=-16); however, there was a significant difference by week 12 (ΔCDAI=-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.
  
  
  
  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.
  
  
  
  NCT01203631.
authors.affiliation: Department of Gastroenterology, APHP, Hôpital Saint Louis, INSERM UMRS 1160, Paris Diderot, Sorbonne Paris-Cité University, Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Allez
authors.affiliation: Novo Nordisk, Inc., Princeton, New Jersey, USA.
authors.forename: Brett E
authors.initials: BE
authors.lastname: Skolnick
authors.affiliation: Department of Gastroenterology, Medical University of Lodz, Lodz, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Wisniewska-Jarosinska
authors.affiliation: NZOZ Vivamed, Warsaw, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Petryka
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Rune Viig
authors.initials: RV
authors.lastname: Overgaard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; C000624132:NNC0142-0002 monoclonal antibody
keywords: CROHN'S DISEASE