Anti-NKG2D monoclonal antibody (NNC0142-0002) in active Crohn's disease: a randomised controlled trial.

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.

• Authors: Matthieu Allez, Brett E Skolnick, Maria Wisniewska-Jarosinska, Robert Petryka, Rune Viig Overgaard
• Journal: Gut (Gut) Vol. 66 Issue 11 Pg. 1918-1925 (11 2017) ISSN: 1468-3288 [Electronic] England
• PMID: 27489241 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: 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/.

Chemical References

• Antibodies, Monoclonal
• Immunoglobulin G
• Immunosuppressive Agents
• KLRK1 protein, human
• NK Cell Lectin-Like Receptor Subfamily K
• NNC0142-0002 monoclonal antibody

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal (therapeutic use)
• Crohn Disease (drug therapy, immunology)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Immunoglobulin G (therapeutic use)
• Immunosuppressive Agents (therapeutic use)
• Injections, Subcutaneous
• Male
• Middle Aged
• NK Cell Lectin-Like Receptor Subfamily K (immunology)
• Treatment Outcome
• Young Adult