Clinical trial NCT05574010: A Study of Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of KAN-101 in Celiac Disease (ACeD-it)
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Celiac Disease
Keywords: celiac disease
HLA-DQ2.5
gluten free diet
Lead sponsor: Anokion SA
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2022-10-10
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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 and Part C: These parts of the study have a randomized, double- blinded, placebo-controlled, parallel study design.
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence and severity of TEAEs as assessed by common terminology criteria for adverse events (CTCAE) in Part A
timeFrame: 28 days
measure: Change in magnitude of IL-2 response pre- and post-GC in peripheral blood in Part B
timeFrame: Baseline to Day 15
measure: Change in magnitude of IL-2 response pre- and post-GC in peripheral blood
timeFrame: 0 (pre-GC) and 4 hours post-GC on Day 15
Secondary outcomes:
measure: KAN-101 plasma exposure in Part A: AUCinf
timeFrame: 0 (pre-dose) and up to 7 hours post dose
measure: KAN-101 plasma exposure in Part A: AUClast
timeFrame: 0 (pre-dose) and up to 7 hours post dose
measure: KAN-101 plasma exposure in Part A: Cmax
timeFrame: 0 (pre-dose) and up to 7 hours post dose
measure: KAN-101 plasma exposure in Part A: Tmax
timeFrame: 0 (pre-dose) and up to 7 hours post dose
measure: KAN-101 plasma exposure in Part A: t½
timeFrame: 0 (pre-dose) and up to 7 hours post dose
measure: KAN-101 plasma exposure in Part B and Part C: AUCinf
timeFrame: 0 (pre-dose) and up to 4 hours post dose
measure: KAN-101 plasma exposure in Part B and Part C: AUClast
timeFrame: 0 (pre-dose) and up to 4 hours post dose
measure: KAN-101 plasma exposure in Part B and Part C: Cmax
timeFrame: 0 (pre-dose) and up to 4 hours post dose
measure: KAN-101 plasma exposure in Part B and Part C: Tmax
timeFrame: 0 (pre-dose) and up to 4 hours post dose
measure: KAN-101 plasma exposure in Part B and Part C: t½
timeFrame: 0 (pre-dose) and up to 4 hours post dose
measure: Incidence and severity of TEAE as assessed by the CTCAE in Part B and Part C.
timeFrame: Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Saint Petersburg
country: United States
facility: GCP Research
state: Florida
city: Sandy Springs
country: United States
facility: Agile Clinical Research Trials
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Normal
country: United States
facility: Sneeze, Wheeze & Itch Associates, LLC
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health University Hospital
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Paul
country: United States
facility: Prism Research LLC dba Nucleus Network
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Quality Clinical Research
state: Nebraska
city: New York
country: United States
facility: Celiac Disease Center at Columbia University
state: New York
city: Raleigh
country: United States
facility: North Carolina Clinical Research
state: North Carolina
city: Columbus
country: United States
facility: Aventiv Research, Inc. d/b/a Centricity Research
state: Ohio
city: Mentor
country: United States
facility: Great Lakes Gastroenterology Research, LLC
state: Ohio
city: Westlake
country: United States
facility: Northshore Gastroenterology Research, LLC
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Waco
country: United States
facility: Digestive Research of Central Texas
state: Texas
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: West Jordan
country: United States
facility: Velocity Clinical Research, Salt Lake City
state: Utah
city: Campbelltown
country: Australia
facility: Campbelltown Hospital
state: New South Wales
city: Auchenflower
country: Australia
facility: Wesley Research Institute
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Midland
country: Australia
facility: St John of God Midland Public and Private Hospitals
state: Western Australia
city: Takapuna
country: New Zealand
facility: PCRN Trials
state: Auckland
city: Tauranga
country: New Zealand
facility: P3 Research - Tauranga
state: Bay Of Plenty
city: Dunedin
country: New Zealand
facility: P3 Research - Dunedin
state: Otago
city: Paraparaumu
country: New Zealand
facility: P3 Research - Palmerston North
state: Wellington
city: Auckland
country: New Zealand
facility: Optimal Clinical Trials
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Wellington
country: New Zealand
facility: P3 Research - Wellington
Study officials:
affiliation: Anokion SA
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.