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).
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
128
Dose 1 KAN-101 Intravenous (IV) infusion
Dose 2 KAN-101 Intravenous (IV) infusion
Placebo Intravenous (IV) infusion
Incidence and Severity of TEAEs as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) in Part A
An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated; Grade 5= death related to AE.
Time frame: From screening until the safety follow-up visit on Day 28
Change in Pre- and Post-Gluten Challenge (GC) IL-2 Response From Baseline to Day 15
CeD increases the circulating level of IL-2. Plasma samples were collected to assess the magnitude of biomarker response of IL-2 at the baseline screening visit pre-GC and again post-GC on Day 15 after 3 doses of KAN-101, the IL-2 response to GC is the difference of IL-2 between pre-GC and post-GC.
Time frame: From Baseline screening to Day 15
Change in IL-2 Response From Day 15 Pre-GC to Day 15 Post GC
CeD increases the circulating level of IL-2. Plasma samples were collected to assess the magnitude of biomarker response of IL-2 at the baseline screening visit pre-GC and again post-GC on Day 15 after 3 doses of KAN-101, the IL-2 response to GC is the difference of IL-2 between pre-GC and post-GC.
Time frame: 0 (pre-GC) and 4 hours post-GC on Day 15
KAN-101 Plasma Exposure in Part A: AUCinf
PK sample collection at pre- dose and post dose timepoints in Part A.
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Dose 3 KAN-101 Intravenous (IV) infusion
Dose 4 KAN-101 Intravenous (IV) infusion
Dose 5 KAN-101 Intravenous (IV) infusion
University of Alabama at Birmingham
Birmingham, Alabama, United States
Anaheim Clinical Trials, LLC
Anaheim, California, United States
GCP Research
St. Petersburg, Florida, United States
Agile Clinical Research Trials
Sandy Springs, Georgia, United States
Rush University Medical Center
Chicago, Illinois, United States
Sneeze, Wheeze & Itch Associates, LLC
Normal, Illinois, United States
Indiana University Health University Hospital
Indianapolis, Indiana, United States
University of Iowa
Iowa City, Iowa, United States
Mayo Clinic
Rochester, Minnesota, United States
Prism Research LLC dba Nucleus Network
Saint Paul, Minnesota, United States
...and 26 more locations
Time frame: Pre-dose, end of infusion, 45 minutes, 1 hour, 1.5 hour, 2.5 hours, 4.5 hours and 7 hours after infusion start on Day 1 and Day 7
KAN-101 Plasma Exposure in Part A: AUClast
PK sample collection at pre- dose and post dose timepoints in Part A.
Time frame: Pre-dose, end of infusion, 45 minutes, 1 hour, 1.5 hour, 2.5 hours, 4.5 hours and 7 hours after infusion start on Day 1 and Day 7
KAN-101 Plasma Exposure in Part A: Cmax
PK sample collection at pre- dose and post dose timepoints in Part A.
Time frame: Pre-dose, end of infusion, 45 minutes, 1 hour, 1.5 hour, 2.5 hours, 4.5 hours and 7 hours after infusion start on Day 1 and Day 7
KAN-101 Plasma Exposure in Part A: Tmax
PK sample collection at pre- dose and post dose timepoints in Part A.
Time frame: Pre-dose, end of infusion, 45 minutes, 1 hour, 1.5 hour, 2.5 hours, 4.5 hours and 7 hours after infusion start on Day 1 and Day 7
KAN-101 Plasma Exposure in Part A: t½
PK sample collection at pre- dose and post dose timepoints in Part A.
Time frame: Pre-dose, end of infusion, 45 minutes, 1 hour, 1.5 hour, 2.5 hours, 4.5 hours and 7 hours after infusion start on Day 1 and Day 7
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.
Time frame: Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7
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.
Time frame: Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7
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.
Time frame: Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7
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.
Time frame: Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7
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.
Time frame: Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7
Incidence and Severity of TEAE as Assessed by the CTCAE in Part B
An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated; Grade 5= death related to AE.
Time frame: From the time the participant provided informed consent through Week 52
Incidence and Severity of TEAE as Assessed by the CTCAE in Part C
An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated; Grade 5= death related to AE.
Time frame: From the time the participant provided informed consent through Week 52