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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}aphp.fr

    Abstract

    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.

    • CROHN'S DISEASE

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