Article Text

Download PDFPDF
Original article
Anti-NKG2D monoclonal antibody (NNC0142-0002) in active Crohn's disease: a randomised controlled trial
  1. Matthieu Allez1,
  2. Brett E Skolnick2,
  3. Maria Wisniewska-Jarosinska3,
  4. Robert Petryka4,
  5. Rune Viig Overgaard5
    1. 1Department of Gastroenterology, APHP, Hôpital Saint Louis, INSERM UMRS 1160, Paris Diderot, Sorbonne Paris-Cité University, Paris, France
    2. 2Novo Nordisk, Inc., Princeton, New Jersey, USA
    3. 3Department of Gastroenterology, Medical University of Lodz, Lodz, Poland
    4. 4NZOZ Vivamed, Warsaw, Poland
    5. 5Novo Nordisk A/S, Søborg, Denmark
    1. Correspondence to Professor Matthieu Allez, Department of Gastroenterology, Hôpital Saint-Louis, 1, Avenue Claude Vellefaux, Paris 75010, France; matthieu.allez{at}


    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 (ΔCDAI) 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 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.

    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.


    Statistics from

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.