Elevated Poster Presentation International Celiac Disease Symposium 2026

Safety and Efficacy of TAK-101: Results from a Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Phase 2 Trial in Patients with Celiac Disease on a Gluten-Free Diet (147095)

Jocelyn A Silvester 1 2 , Joseph A Murray 3 , Jason A Tye-Din 4 5 , Avigayil Rapp 6 , Rishi Shah 7 , Florin Gaidici 8 , Ciarán P Kelly 2 , William J McAuliffe 9 , Sonal Ghura 9 , Shan Xiao 9 , Mahsa Zarei 9 , Joseph R Maxwell 9 , Michael Nome 9 , James Canavan 9
  1. Boston Children’s Hospital, Boston, MA, USA
  2. Beth Israel Deaconess Medical Center, Boston, MA, USA
  3. Mayo Clinic, Rochester, MN, USA
  4. Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
  5. Department of Gastroenterology, The Royal Melbourne Hospital, Melbourne, Australia
  6. Basil Clinical, Queens, NY, USA
  7. Emeritus Research, Melbourne, Australia
  8. 1-OAK (One of a Kind Clinical Research Center), Scottsdale, AZ, USA
  9. Takeda Development Center Americas, Inc., Cambridge, MA, USA

Introduction: TAK-101 is an antigen-containing nanoparticle designed to induce gluten-specific tolerance in patients with celiac disease (CeD). Here, we report topline results from the phase 2 study of TAK-101.

Methods: The study included HLA-DQ2.5- and/or DQ8-positive adults (>18 years) with biopsy-proven CeD, on a gluten-free diet for ≥6 months with mild-to-no symptoms. Patients were randomized to receive placebo or TAK-101 intravenously (12.5, 25.0, or 50.0µg/kg) on Days (D) 1 and 8, and TAK-101 at Week 24. Patients received a single high-dose gluten challenge (GC) during run-in (3g), D15–17 (12g), D18–20 (6g), and at the beginning of Weeks 8, 14, and 20 (3g each). The primary endpoint was change from baseline (D15; start of the 6-day high-dose GC) to D20 in T-cell–mediated, gluten-stimulated interferon (IFN)-γ production, determined by a gliadin-specific enzyme-linked immunospot (ELISpot) assay. Safety endpoints included treatment-emergent adverse events (TEAEs) and immunogenicity.

Results: Of 232 screened patients, 102 were randomized and 91 completed the study. Patients were predominantly female, white, and ≥40 years. Gluten intake during GC was confirmed by self-reporting and measurement of urinary gluten immunogenic peptide. Immunological responses to GC, defined by a twofold increase in serum interleukin-2 expression at 4 hours post-GC, were observed in 72.3% of patients during run-in (3g GC), and in 89.7% on D15 (12g GC). However, there was no significant increase in the proportion of gut-homing T cells or IFN‑γ production following the 6-day high-dose GC (D15–20), in any group. Consequently, the primary endpoint measures were not interpretable. No new safety signals and no serious TEAEs were observed.

Conclusion: TAK-101 was generally well tolerated, but the expected T-cell response to a 6-day high-dose GC was not observed in the placebo group, rendering the primary endpoint data uninterpretable, highlighting considerations for future CeD studies.