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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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)

Conditions
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Celiac Disease

Intervention / Treatment
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* Drug: Cohort 1 in Part A
* Drug: Cohort 2 in Part A
* Other: Placebo: Group 1 in Part B
* Drug: Group 2 in Part B
* Drug: Group 3 in Part B
* Drug: Group 4 in Part B


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 in Part A<br>All eligible Part A participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 1 | Drug: Cohort 1 in Part A<br>* Dose 1 KAN-101 Intravenous (IV) infusion<br>* Other names: KAN-101;|
| Experimental: Cohort 2 in Part A<br>All eligible Part A participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 2 | Drug: Cohort 2 in Part A<br>* Dose 2 KAN-101 Intravenous (IV) infusion<br>* Other names: KAN-101;|
| Placebo Comparator: Group 1 in Part B<br>All eligible Part B participants will receive 3 intravenous (IV) infusions of placebo | Other: Placebo: Group 1 in Part B<br>* Placebo Intravenous (IV) infusion<br>* Other names: Placebo;|
| Experimental: Group 2 in Part B<br>All eligible Part B participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 3 | Drug: Group 2 in Part B<br>* Dose 3 KAN-101 Intravenous (IV) infusion<br>* Other names: KAN-101;|
| Experimental: Group 3 in Part B<br>All eligible Part B participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 4 | Drug: Group 3 in Part B<br>* Dose 4 KAN-101 Intravenous (IV) infusion<br>* Other names: KAN-101;|
| Experimental: Group 4 in Part B<br>All eligible Part B participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 5 | Drug: Group 4 in Part B<br>* Dose 5 KAN-101 Intravenous (IV) infusion<br>* Other names: KAN-101;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of TEAEs as assessed by common terminology criteria for adverse events (CTCAE) in Part A | Primary endpoint in Part A. CTCAE is a scale with 5 grades to assess AE severity. | 28 days | 
| Change in magnitude of IL-2 response pre- and post-GC in peripheral blood in Part B | Primary endpoint in Part B. | Baseline to Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| KAN-101 plasma exposure in Part A: AUCinf | PK sample collection at pre- dose and post dose timepoints in Part A. | 0 (pre-dose) and up to 7 hours post dose | 
| KAN-101 plasma exposure in Part A: AUClast | PK sample collection at pre- dose and post dose timepoints in Part A. | 0 (pre-dose) and up to 7 hours post dose | 
| KAN-101 plasma exposure in Part A: Cmax | PK sample collection at pre- dose and post dose timepoints in Part A. | 0 (pre-dose) and up to 7 hours post dose | 
| KAN-101 plasma exposure in Part A: Tmax | PK sample collection at pre- dose and post dose timepoints in Part A. | 0 (pre-dose) and up to 7 hours post dose | 
| KAN-101 plasma exposure in Part A: t½ | PK sample collection at pre- dose and post dose timepoints in Part A. | 0 (pre-dose) and up to 7 hours post dose | 
| KAN-101 plasma exposure in Part B: AUCinf | PK sample collection at pre- dose and post dose timepoints in Part B | 0 (pre-dose) and up to 4 hours post dose | 
| KAN-101 plasma exposure in Part B: AUClast | PK sample collection at pre- dose and post dose timepoints in Part B. | 0 (pre-dose) and up to 4 hours post dose | 
| KAN-101 plasma exposure in Part B: Cmax | PK sample collection at pre- dose and post dose timepoints in Part B. | 0 (pre-dose) and up to 4 hours post dose | 
| KAN-101 plasma exposure in Part B: Tmax | PK sample collection at pre- dose and post dose timepoints in Part B. | 0 (pre-dose) and up to 4 hours post dose | 
| KAN-101 plasma exposure in Part B: t½ | PK sample collection at pre- dose and post dose timepoints in Part B. | 0 (pre-dose) and up to 4 hours post dose | 
| Incidence and severity of TEAE as assessed by the CTCAE in Part B. | Secondary endpoint in Part B | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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celiac disease, HLA-DQ2.5, gluten free diet