ASSESSMENT OF KAN-101 IN CED AND IMMUNE TOLERANCE (ACED-IT) STUDY, PH1B DATA WITH HIGHER DOSE LEVELS OF KAN-101, A NOVEL IMMUNE TOLERANCE THERAPY FOR CELIAC DISEASE

Background: Celiac disease (CeD) is a chronic inflammatory disorder triggered and maintained by ingestion of gluten. The only treatment is a gluten-free diet as no pharmaceutical treatment is available. KAN-101 is an investigational therapy composed of a liver-targeting glycosylation signature conjugated to an immunodominant peptide from gliadin. KAN-101 reduces gluten-specific immune responses and modulates GC IL-2, a biomarker reported to be associated with symptomatic reactions, in a first in human (FIH) study in CeD patients¹.
Aim: The Ph1b (Part A) portion of the Assessment of KAN-101 in CeD and Immune Tolerance (ACeD-it) study evaluated safety and tolerability of higher dose levels of KAN-101 than studied in the previous FIH study, thereby enabling evaluation of biomarker and symptom responses to GC in Ph2 (Part B). In addition, KAN-101 pharmacokinetics (PK) and biomarker response to gluten challenge (GC) were collected.
Methods: Part A of ACeD-it was an open-label, multiple ascending dose study. Adult DQ2.5+ patients with biopsy-confirmed CeD received an IV infusion of KAN-101 on Days 1, 4 and 7 at one of 2 dose levels, 1.2 or 3.0 mg/kg. At Day 15, patients received a 1-day GC. Adverse events (AE) were assessed throughout the study. Plasma samples were collected on Days 1 and 7 for pharmacokinetic analysis, as well as both prior to and 4 hours after GC on Day 15 for biomarkers. Day 15 plasma samples were analyzed using a high sensitivity assay for IL-2 and a multiplex immunoassay for other cytokines.
Results: 6 patients were enrolled in Part A. 5 completed the study treatment. One patient withdrew consent prior to receiving the second infusion of study drug on Day 4. One other patient completed study treatment but was unable to complete the Day 15 GC due to COVID-19. All patients reported at least one treatment emergent adverse event (TEAE), each was grade 1 (mild) or grade 2 (moderate) in severity. The majority (14/18) of TEAEs were consistent with symptoms experienced by CeD patients upon ingestion of gluten. No serious adverse events or deaths occurred. The PK profile of KAN-101 shows a short half-life between 11 and 21 minutes and no accumulation with repeated dosing, in line with previous results. Consistent with results from the FIH study, in a portion of patients treated with KAN-101 the broader cytokine response to GC was modulated and associated with a lack of nausea symptoms.
Conclusions: KAN-101 dose levels up to 3mg/kg were safe and tolerated in CeD patients, exhibited a PK profile in keeping with lower dose levels, and modulated cytokine responses after GC, indicating development of immunological tolerance and immunoregulatory responses. These data extend the findings from the Ph1 and provide additional dose levels for inclusion in Ph2.
1. Murray et al. Lancet Gastroenterol Hepatol. 2023 Aug;8(8):735-747