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

The study is a 3-part, multicenter Phase 1b/2 study of KAN-101 in participants with Celiac Disease (CeD) on a gluten free diet (GFD). The 3 parts include:

* Part A - Open-label, multiple ascending dose

* Part B - Double-blind, placebo-controlled, parallel design

* Part C - 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.

Parts B and C are 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. Approximately 16 participants (4 participants per dose group) will be enrolled in Part B and 104 participants (26 participants per dose group) enrolled into Part C. Participants 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.

Primary Outcome Measures

1. Incidence and Severity of TEAEs as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) in Part A
   An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated; Grade 5= death related to AE.
2. Change in Pre- and Post-Gluten Challenge (GC) IL-2 Response From Baseline to Day 15
   CeD increases the circulating level of IL-2. Plasma samples were collected to assess the magnitude of biomarker response of IL-2 at the baseline screening visit pre-GC and again post-GC on Day 15 after 3 doses of KAN-101, the IL-2 response to GC is the difference of IL-2 between pre-GC and post-GC.
3. Change in IL-2 Response From Day 15 Pre-GC to Day 15 Post GC
   CeD increases the circulating level of IL-2. Plasma samples were collected to assess the magnitude of biomarker response of IL-2 at the baseline screening visit pre-GC and again post-GC on Day 15 after 3 doses of KAN-101, the IL-2 response to GC is the difference of IL-2 between pre-GC and post-GC.

Secondary Outcome Measures

1. KAN-101 Plasma Exposure in Part A: AUCinf
   PK sample collection at pre- dose and post dose timepoints in Part A.
2. KAN-101 Plasma Exposure in Part A: AUClast
   PK sample collection at pre- dose and post dose timepoints in Part A.
3. KAN-101 Plasma Exposure in Part A: Cmax
   PK sample collection at pre- dose and post dose timepoints in Part A.
4. KAN-101 Plasma Exposure in Part A: Tmax
   PK sample collection at pre- dose and post dose timepoints in Part A.
5. KAN-101 Plasma Exposure in Part A: t½
   PK sample collection at pre- dose and post dose timepoints in Part A.
6. KAN-101 Plasma Exposure in Part B and Part C: AUCinf
   PK sample collection at pre- dose and post dose timepoints in Part B and Part C.
7. KAN-101 Plasma Exposure in Part B and Part C: AUClast
   PK sample collection at pre- dose and post dose timepoints in Part B and Part C.
8. KAN-101 Plasma Exposure in Part B and Part C: Cmax
   PK sample collection at pre- dose and post dose timepoints in Part B and Part C.
9. KAN-101 Plasma Exposure in Part B and Part C: Tmax
   PK sample collection at pre- dose and post dose timepoints in Part B and Part C.
10. KAN-101 Plasma Exposure in Part B and Part C: t½
    PK sample collection at pre- dose and post dose timepoints in Part B and Part C.
11. Incidence and Severity of TEAE as Assessed by the CTCAE in Part B
    An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated; Grade 5= death related to AE.
12. Incidence and Severity of TEAE as Assessed by the CTCAE in Part C
    An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated; Grade 5= death related to AE.