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

Celiac Disease Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05574010
• Other study ID #: KAN-101-02
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 15, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: June 2024
• Source: Anokion SA
• Contact: Kanyos Bio, Inc. (a wholly owned subsidiary of Anokion S.A.)
• Phone: +1 857-320-6607
• Email: clinicaltrials[@]anokion.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 126
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Celiac Disease

Intervention

Drug:
• Cohort 1 in Part A
Dose 1 KAN-101 Intravenous (IV) infusion
• Cohort 2 in Part A
Dose 2 KAN-101 Intravenous (IV) infusion

Other:
• Placebo: Group 1 in Part B and Part C
Placebo Intravenous (IV) infusion

Drug:
• Group 2 in Part B and Part C
Dose 3 KAN-101 Intravenous (IV) infusion
• Group 3 in Part B and Part C
Dose 4 KAN-101 Intravenous (IV) infusion
• Group 4 in Part B and Part C
Dose 5 KAN-101 Intravenous (IV) infusion

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	St John of God Midland Public and Private Hospitals	Midland	Western Australia
Australia	The Royal Melbourne Hospital	Parkville	Victoria
New Zealand	Optimal Clinical Trials	Auckland
New Zealand	P3 Research - Dunedin	Dunedin	Otago
New Zealand	Waikato Hospital	Hamilton
New Zealand	P3 Research - Hawke's Bay	Hastings	Hawke's Bay
New Zealand	P3 Research - Palmerston North	Paraparaumu	Wellington
New Zealand	PCRN Trials	Takapuna	Auckland
New Zealand	P3 Research - Tauranga	Tauranga	Bay Of Plenty
New Zealand	P3 Research - Wellington	Wellington
United States	Anaheim Clinical Trials, LLC	Anaheim	California
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Aventiv Research, Inc. d/b/a Centricity Research	Columbus	Ohio
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	Indiana University Health University Hospital	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Great Lakes Gastroenterology Research, LLC	Mentor	Ohio
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Sneeze, Wheeze & Itch Associates, LLC	Normal	Illinois
United States	Advanced Research Institute	Ogden	Utah
United States	Quality Clinical Research	Omaha	Nebraska
United States	North Carolina Clinical Research	Raleigh	North Carolina
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Prism Research LLC dba Nucleus Network	Saint Paul	Minnesota
United States	GCP Research	Saint Petersburg	Florida
United States	Agile Clinical Research Trials	Sandy Springs	Georgia
United States	Digestive Research of Central Texas	Waco	Texas
United States	Velocity Clinical Research, Salt Lake City	West Jordan	Utah
United States	Northshore Gastroenterology Research, LLC	Westlake	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Kanyos Bio, Inc., a wholly-owned subsidiary of Anokion SA	Pfizer

Countries where clinical trial is conducted

United States,  Australia,  New Zealand, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Change in magnitude of IL-2 response pre- and post-GC in peripheral blood	Primary endpoint in Part C	0 (pre-GC) and 4 hours post-GC on Day 15
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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	0 (pre-dose) and up to 4 hours post dose
Secondary	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.	0 (pre-dose) and up to 4 hours post dose
Secondary	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.	0 (pre-dose) and up to 4 hours post dose
Secondary	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.	0 (pre-dose) and up to 4 hours post dose
Secondary	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.	0 (pre-dose) and up to 4 hours post dose
Secondary	Incidence and severity of TEAE as assessed by the CTCAE in Part B and Part C.	Secondary endpoint in Part B and Part C	Week 52