Introduction
There is an unmet need for adjunctive therapies for patients with celiac disease (CeD) who experience inadequate disease control while maintaining a gluten-free diet (GFD). The optimal trial design to assess CeD treatment efficacy is unclear and increased adherence to a GFD during trials may improve disease control. We assessed symptom severity changes during the screening and run-in periods (no treatment) of two phase 2b CeD trials, one using simulated inadvertent gluten exposure (SIGE) and one without.
Aims & Methods
In two concurrent ongoing phase 2 CeD trials (NCT05353985 and EudraCT2020-004612-97) daily gastrointestinal (GI) symptom severity was measured using the Celiac Disease Symptom Diary 2.1© during the screening and run-in periods (4 weeks each in NCT05353985; 6 weeks and 5 weeks, respectively in EudraCT2020-004612-97) before any treatment administration. In both trials, eligible patients had biopsy-confirmed CeD and were experiencing CeD-related symptoms and enteropathy despite following a GFD. NCT05353985 included food bars containing ~500 mg gluten, consumed 3-times weekly after Week 2, for 2 weeks during the run-in period (post randomization). EudraCT2020-004612-97 did not include gluten exposure. Mean GI symptom severity scores were calculated each week during the screening and run-in periods.
Results
From the start of the screening period through to the end of the run-in period, mean GI symptom severity scores improved significantly in EudraCT2020-004612-97 (0.96 at Week 1 of screening, and 0.75 at Week 5 of run-in) whereas changes were non-significant in NCT05353985 (0.96 at Week 1 of screening and 0.92 at Week 4 of run-in).
Conclusion
Clinical trial participation may result in an improvement in CeD-related GI symptoms due to better GFD adherence. Administration of SIGE can minimize such trial effects and does not worsen symptoms in patients with CeD.
Disclosure
SB, NC, AH, DAL and QL are employees and shareholders of Takeda.
KH RM and RM are employees of Dr. Falk Pharma GmbH.
JM reports grants (to institution) from, National Institutes of Health, Immunogenix, Takeda Pharmaceutical, Allakos, ProventionBio, Oberkotter Foundation, and 9Meters, Inc.; contract (to institution) from Kanyos Bio (a wholly owned subsidiary of Anokion); and consultancy fees from Johnson and Johnson, Bristol Myers Squibb, Intrexon Corporation, Dren Bio, Neoleukin, Reistone pharma, GSK, Immunic Therapeutics, Brightseed Bio, Chugai Pharma, Alimentiv, Equillium, Ukko, Medibeacon, Israel Biotech Fund, Precigen, triangle insights group, Sanofi, Zag Bio, Loop bio and Orbimed; and has received royalties from Evelo. MS has no funding to disclose relating to this study and is the Principal Investigator in the EudraCT2020-004612-97 clinical trial.
MS has no funding to disclose relating to this study and is the Principal Investigator in the EudraCT2020-004612-97 clinical trial.
ML receives research funding from Takeda and Moderna, and has previously acted as a consultant for Anokion and Amgen.
JS reports grants (to institution) from Celiac Disease Foundation, National Institutes of Health, Takeda Pharmaceutical, Allan Foundation and consultancy fees from Alimentiv and Takeda Pharmaceuticals.
DS received study related management/advisory fees from Dr. Falk Pharma.
