A Study of Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of KAN-101 in Celiac Disease (ACeD-it)

A Study of Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of KAN-101 in Celiac Disease (ACeD-it)

A Phase 1B Open-label/Phase 2 Double-blind Placebo- Controlled Study for Pharmacodynamic (PD) Activity, Pharmacokinetics (PK), Safety, and Tolerability of KAN-101 In Patients With Celiac Disease (CeD)

This study is to evaluate the Pharmacodynamic (PD), safety, tolerability, Pharmacokinetic (PK), and plasma biomarker response of KAN-101 in participants with Celiac Disease (CeD).

The study is a 2-part, multicenter Phase 1b/2 study of KAN-101 in participants with Celiac Disease (CeD) on a gluten free diet (GFD). The 2 parts include: Part A - Open-label, multiple ascending dose Part B - Double-blind, placebo-controlled, parallel design Part A is a Phase 1b, open-label, multiple ascending dose (MAD) study design to assess the safety, tolerability, and pharmacokinetics (PK) of KAN-101 in adult participants (18 to 70 years inclusive) with histology-confirmed CeD. Up to 12 participants who meet study inclusion/exclusion criteria will receive 1 of 2 dose levels of KAN-101. The overall study duration will be about 56 days, including up to 28 days of screening, 7 days of treatment and 21 days of follow up. There will be a gluten challenge test (GC) on Day 15. Part B is a Phase 2, double-blind, placebo-controlled, parallel design study to characterize the biomarker response following GC, safety, tolerability, and PK of KAN-101 in adult participants with histology-confirmed CeD. 120 participants (30 participants per dose group) will be randomized 1:1:1:1 and stratified by participation in a biopsy substudy to 4 treatment groups: placebo and 3 treatment groups with KAN-101 doses based on information obtained from Part A.

Part A: This part of the study is an open label with up to 6 participants in each dose cohort. There will be 2 dose cohorts. Part B: This part of the study has a randomized, double- blinded, placebo-controlled, parallel study design.

Part A is open label Part B is a double-blinded study. Study participants and their caregivers, investigators and other site staff, and sponsor staff involved in the study team will be blinded.

Incidence and severity of TEAEs as assessed by common terminology criteria for adverse events (CTCAE) in Part A

Inclusion Criteria: Previous diagnosis of celiac disease based on histology and positive celiac serology HLA-DQ2.5 genotype Gluten-free diet for at least 12 months Negative or weak positive for transglutaminase IgA and negative or weak positive for DGP-IgA/IgG during screening Exclusion Criteria: Refractory celiac disease HLA-DQ8 genotype Previous oral gluten challenge within 12 months Selective IgA deficiency Diagnosis of Type-1 diabetes Active gastrointestinal diseases History of dermatitis herpetiformis

Murray JA, Wassaf D, Dunn K, Arora S, Winkle P, Stacey H, Cooper S, Goldstein KE, Manchanda R, Kontos S, Grebe KM. Safety and tolerability of KAN-101, a liver-targeted immune tolerance therapy, in patients with coeliac disease (ACeD): a phase 1 trial. Lancet Gastroenterol Hepatol. 2023 Aug;8(8):735-747. doi: 10.1016/S2468-1253(23)00107-3. Epub 2023 Jun 14.