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

• ClinicalTrials.gov Identifier: NCT05574010
• Recruitment Status: Recruiting
• First Posted: October 10, 2022
• Last Update Posted: May 6, 2024
• Sponsor: Kanyos Bio, Inc., a wholly-owned subsidiary of Anokion SA
• Collaborator: Pfizer
• Information provided by (Responsible Party): Anokion SA ( Kanyos Bio, Inc., a wholly-owned subsidiary of Anokion SA )

Tracking Information

• First Submitted Date: October 7, 2022
• First Posted Date: October 10, 2022
• Last Update Posted Date: May 6, 2024
• Actual Study Start Date: November 15, 2022
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 18, 2024)

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

Original Primary Outcome Measures (submitted: October 7, 2022)

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

Current Secondary Outcome Measures (submitted: March 18, 2024)

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

Original Secondary Outcome Measures (submitted: October 7, 2022)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

Part A is open label Part B and Part C are a double-blinded study. Study participants and their caregivers, investigators and other site staff, and sponsor staff involved in the study team will be blinded.

Primary Purpose: Treatment

• Condition: Celiac Disease

Intervention

• Drug: Cohort 1 in Part A
  Dose 1 KAN-101 Intravenous (IV) infusion
  Other Name: KAN-101
• Drug: Cohort 2 in Part A
  Dose 2 KAN-101 Intravenous (IV) infusion
  Other Name: KAN-101
• Other: Placebo: Group 1 in Part B and Part C
  Placebo Intravenous (IV) infusion
  Other Name: Placebo
• Drug: Group 2 in Part B and Part C
  Dose 3 KAN-101 Intravenous (IV) infusion
  Other Name: KAN-101
• Drug: Group 3 in Part B and Part C
  Dose 4 KAN-101 Intravenous (IV) infusion
  Other Name: KAN-101
• Drug: Group 4 in Part B and Part C
  Dose 5 KAN-101 Intravenous (IV) infusion
  Other Name: KAN-101

Study Arms

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

• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 18, 2024): 126
• Original Estimated Enrollment (submitted: October 7, 2022): 138
• Estimated Study Completion Date: December 31, 2025
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Kanyos Bio, Inc. (a wholly owned subsidiary of Anokion S.A.); +1 857-320-6607; clinicaltrials@anokion.com

• Listed Location Countries: Australia, New Zealand, United States

Administrative Information

• NCT Number: NCT05574010
• Other Study ID Numbers: KAN-101-02
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Anokion SA ( Kanyos Bio, Inc., a wholly-owned subsidiary of Anokion SA )
• Original Responsible Party: Same as current
• Current Study Sponsor: Kanyos Bio, Inc., a wholly-owned subsidiary of Anokion SA
• Original Study Sponsor: Same as current
• Collaborators: Pfizer

Investigators

• Study Director: Study Director; Anokion SA

• PRS Account: Anokion SA
• Verification Date: May 2024