Oral Presentation International Celiac Disease Symposium 2026

A Randomized, Double-Blind, Placebo-Controlled, Biological Proof-of-Concept Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Biological Effects of DONQ52 in Celiac Disease Patients with Gluten Challenge (the DQB103CT Study) (147054)

Jason Tye-Din 1 , Gerald Holtmann 2 , Vincent Ho 3 , Indika Leelasena 4 , Dean Quinn 5 , Yosuke Murakami 6 , Koichiro Yoneyama 6 , Kosuke Yamashita 6 , Ichio Ohnami 6 , Kazuaki Yoshimura 6 , Atsuo Kurata 6 , Azusa Yokota 6 , HIsayoshi Nanmo 6 , Shinta Kobayashi 7 , Daniel Leffler 7 , Joseph A Murray 8
  1. Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
  2. The University of Queensland - Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
  3. Campbelltown Hospital, Campbelltown, New South Wales, Australia
  4. University of the Sunshine Coast Clinical Trials Moreton Bay, Petrie, Queensland, Australia
  5. Momentum Wellington, Wellington Central, Wellington , New Zealand
  6. Chugai Pharmaceutical, Tokyo, TOKYO, Japan
  7. Chugai Pharma USA, Berkeley Heights, New Jersey, USA
  8. Mayo Clinic in Rochester, Rochester, Minnesota, USA

Background

DONQ52 is a humanized monoclonal antibody with a multi-specific structure designed to prevent T cell activation by specifically binding to complexes formed by HLA-DQ2.5 and gluten peptides for the treatment of celiac disease (CeD). This biological proof-of-concept study (DQB103CT; ACTRN12624000316505) evaluated the safety, tolerability, pharmacokinetics (PK), and biological effects of DONQ52 on gluten-induced immune responses.

Methods

DQB103CT evaluated biopsy-proven CeD patients with HLA-DQ2.5 in the absence of DQ2.2 or DQ8 (Part A), and with HLA-DQ2.2 or DQ8 in the presence or absence of HLA-DQ2.5 (Part B). Patients were administered a single dose of 2 mg/kg of DONQ52 or placebo subcutaneously, followed 8 days later by a 10 g/day wheat gluten challenge for 3 days.

Results

Part A and Part B enrolled 41 and 22 patients, respectively. DONQ52 demonstrated an intended exposure with no obvious effect of gluten challenge on PK. Treatment-emergent adverse events occurred in 100% (32/32) of the DONQ52 group and 87.1% (27/31) of the placebo group. Adverse drug reactions (ADRs) were reported in 28.1% (9/32) of patients receiving DONQ52 and 54.8% (17/31) of patients receiving placebo. All ADRs in the DONQ52 group were Grade 1 in severity, whereas ADRs in the placebo group were Grade 1 or Grade 2. In Part A, DONQ52 reduced the baseline change in interferon-gamma spot-forming units versus placebo. DONQ52 also suppressed increases in circulating CD38+Tetramer+CD4+ T-cells and gut-homing CD8+ T-cells, and completely abolished IL-2 induction in whole blood assays. In Part B patients with HLA-DQ2.5 and DQ2.2, DONQ52 showed a suppressive tendency in gut-homing CD8+ T-cells and significantly suppressed ex-vivo IL-2 induction.

Conclusion

DONQ52 targeting complexes formed by HLA-DQ2.5 and gluten peptides has favorable safety, tolerability, and PK profiles during gluten exposure. The observed inhibition of gluten-induced T-cell activation aligns with non-clinical data, supporting further clinical development of DONQ52 for CeD.