Study Description

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.

Condition or Disease	Intervention/Treatment
Celiac Disease	Drug: Cohort 1 in Part A Drug: Cohort 2 in Part A Other: Placebo: Group 1 in Part B and Part C Drug: Group 2 in Part B and Part C Drug: Group 3 in Part B and Part C Drug: Group 4 in Part B and Part C

Study Design

Study Type	Interventional
Anticipated Enrollment	126 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Triple
Primary Purpose	Treatment
Official Title	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)
Study Start Date	November 15, 2022
Anticipated Primary Completion Date	December 31, 2024
Anticipated Study Completion Date	December 31, 2025

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
Cohort 1 in Part A All eligible Part A participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 1	Drug: Cohort 1 in Part A Dose 1 KAN-101 Intravenous (IV) infusion
Cohort 2 in Part A All eligible Part A participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 2	Drug: Cohort 2 in Part A
Group 1 in Part B and Part C All eligible Part B and Part C participants will receive 3 intravenous (IV) infusions of placebo	Other: Placebo: Group 1 in Part B and Part C
Group 2 in Part B and Part C All eligible Part B and Part C participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 3	Drug: Group 2 in Part B and Part C
Group 3 in Part B and Part C All eligible Part B and Part C participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 4	Drug: Group 3 in Part B and Part C
Group 4 in Part B and Part C All eligible Part B and Part C participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 5	Drug: Group 4 in Part B and Part C

Outcome Measures

Primary Outcome Measures

1. Incidence and severity of TEAEs as assessed by common terminology criteria for adverse events (CTCAE) in Part A [28 days]
   Primary endpoint in Part A. CTCAE is a scale with 5 grades to assess AE severity.
2. Change in magnitude of IL-2 response pre- and post-GC in peripheral blood in Part B [Baseline to Day 15]
   Primary endpoint in Part B
3. Change in magnitude of IL-2 response pre- and post-GC in peripheral blood [0 (pre-GC) and 4 hours post-GC on Day 15]
   Primary endpoint in Part C

Secondary Outcome Measures

1. KAN-101 plasma exposure in Part A: AUCinf [0 (pre-dose) and up to 7 hours post dose]
   PK sample collection at pre- dose and post dose timepoints in Part A.
2. KAN-101 plasma exposure in Part A: AUClast [0 (pre-dose) and up to 7 hours post dose]
   PK sample collection at pre- dose and post dose timepoints in Part A.
3. KAN-101 plasma exposure in Part A: Cmax [0 (pre-dose) and up to 7 hours post dose]
   PK sample collection at pre- dose and post dose timepoints in Part A.
4. KAN-101 plasma exposure in Part A: Tmax [0 (pre-dose) and up to 7 hours post dose]
   PK sample collection at pre- dose and post dose timepoints in Part A.
5. KAN-101 plasma exposure in Part A: t½ [0 (pre-dose) and up to 7 hours post dose]
   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 [0 (pre-dose) and up to 4 hours post dose]
   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 [0 (pre-dose) and up to 4 hours post dose]
   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 [0 (pre-dose) and up to 4 hours post dose]
   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 [0 (pre-dose) and up to 4 hours post dose]
   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 [0 (pre-dose) and up to 4 hours post dose]
    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 and Part C. [Week 52]
    Secondary endpoint in Part B and Part C

Eligibility Criteria

Ages Eligible for Study	18 Years to 70 Years (Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	No
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

Contacts and Locations

Sponsors and Collaborators	Kanyos Bio, Inc., a wholly-owned subsidiary of Anokion SA, Pfizer
	Pfizer
Locations	University of Alabama at Birmingham | Birmingham, Alabama, United States, 35233 Anaheim Clinical Trials, LLC | Anaheim, California, United States, 92801 GCP Research | Saint Petersburg, Florida, United States, 33705 Agile Clinical Research Trials | Sandy Springs, Georgia, United States, 30328 Sneeze, Wheeze & Itch Associates, LLC | Normal, Illinois, United States, 61761 Indiana University Health University Hospital | Indianapolis, Indiana, United States, 46202 University of Iowa | Iowa City, Iowa, United States, 52242 Mayo Clinic | Rochester, Minnesota, United States, 55905 Prism Research LLC dba Nucleus Network | Saint Paul, Minnesota, United States, 55114 Washington University School of Medicine | Saint Louis, Missouri, United States, 63110 Quality Clinical Research | Omaha, Nebraska, United States, 68114 Celiac Disease Center at Columbia University | New York, New York, United States, 10032 North Carolina Clinical Research | Raleigh, North Carolina, United States, 27607 Aventiv Research, Inc. d/b/a Centricity Research | Columbus, Ohio, United States, 43213 Great Lakes Gastroenterology Research, LLC | Mentor, Ohio, United States, 44060 Northshore Gastroenterology Research, LLC | Westlake, Ohio, United States, 44145 Penn State Milton S. Hershey Medical Center | Hershey, Pennsylvania, United States, 17033 Vanderbilt University Medical Center | Nashville, Tennessee, United States, 37212 The University of Texas Health Science Center at Houston | Houston, Texas, United States, 77030 Digestive Research of Central Texas | Waco, Texas, United States, 76712 Advanced Research Institute | Ogden, Utah, United States, 84405 Velocity Clinical Research, Salt Lake City | West Jordan, Utah, United States, 84088 Campbelltown Hospital | Campbelltown, New South Wales, Australia, 2560 Wesley Research Institute | Auchenflower, Queensland, Australia, 4066 Royal Adelaide Hospital | Adelaide, South Australia, Australia, 5000 Box Hill Hospital | Box Hill, Victoria, Australia, 3128 The Royal Melbourne Hospital | Parkville, Victoria, Australia, 3050 St John of God Midland Public and Private Hospitals | Midland, Western Australia, Australia, 6056 PCRN Trials | Takapuna, Auckland, New Zealand, 0622 P3 Research - Tauranga | Tauranga, Bay Of Plenty, New Zealand, 3110 P3 Research - Hawke's Bay | Hastings, Hawke's Bay, New Zealand, 4122 P3 Research - Dunedin | Dunedin, Otago, New Zealand, 9016 P3 Research - Palmerston North | Paraparaumu, Wellington, New Zealand, 5032 Optimal Clinical Trials | Auckland, New Zealand, 1023 Waikato Hospital | Hamilton, New Zealand, 3204 P3 Research - Wellington | Wellington, New Zealand, 6021
Investigators

More Information

Publications

• 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.

Additional Relevant MeSH Terms

• Celiac Disease
• Malabsorption Syndromes
• Intestinal Diseases
• Gastrointestinal Diseases
• Digestive System Diseases
• Metabolic Diseases