Celiac Disease
Conditions
Keywords
celiac disease, HLA-DQ2.5, gluten free diet
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.
Interventions
DRUGCohort 1 in Part A
Dose 1 KAN-101 Intravenous (IV) infusion
DRUGCohort 2 in Part A
Dose 2 KAN-101 Intravenous (IV) infusion
OTHERPlacebo: Group 1 in Part B and Part C
Placebo Intravenous (IV) infusion
DRUGGroup 2 in Part B and Part C
Dose 3 KAN-101 Intravenous (IV) infusion
DRUGGroup 3 in Part B and Part C
Dose 4 KAN-101 Intravenous (IV) infusion
DRUGGroup 4 in Part B and Part C
Dose 5 KAN-101 Intravenous (IV) infusion
Sponsors
Kanyos Bio, Inc., a wholly-owned subsidiary of Anokion SA
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, 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.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of TEAEs as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) in Part A | From screening until the safety follow-up visit on Day 28 | 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. |
| Change in Pre- and Post-Gluten Challenge (GC) IL-2 Response From Baseline to Day 15 | From Baseline screening 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. |
| Change in IL-2 Response From Day 15 Pre-GC to Day 15 Post GC | 0 (pre-GC) and 4 hours post-GC on 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| KAN-101 Plasma Exposure in Part A: AUCinf | 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 | PK sample collection at pre- dose and post dose timepoints in Part A. |
| KAN-101 Plasma Exposure in Part A: AUClast | 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 | PK sample collection at pre- dose and post dose timepoints in Part A. |
| KAN-101 Plasma Exposure in Part A: Cmax | 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 | PK sample collection at pre- dose and post dose timepoints in Part A. |
| KAN-101 Plasma Exposure in Part A: Tmax | 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 | PK sample collection at pre- dose and post dose timepoints in Part A. |
| KAN-101 Plasma Exposure in Part A: t½ | 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 | PK sample collection at pre- dose and post dose timepoints in Part A. |
| KAN-101 Plasma Exposure in Part B and Part C: AUCinf | Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7 | 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 | Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7 | 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 | Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7 | 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 | Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7 | 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 | Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7 | 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 | From the time the participant provided informed consent through Week 52 | 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. |
| Incidence and Severity of TEAE as Assessed by the CTCAE in Part C | From the time the participant provided informed consent through Week 52 | 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. |
Countries
Australia, New Zealand, United States
Contacts
STUDY_DIRECTORStudy Director
Anokion SA
Participant flow
Pre-assignment details
Safety Analysis Set includes all participants who received any portion of study intervention in Parts A, B and C. Participants were analyzed according to the intervention they actually received. In Part B, a total of 11 participants were assigned to the KAN-101 treatment groups, and only 10 received study intervention. In Part C, a total of 80 participants were assigned to the KAN-101 treatment groups, and only 79 received study intervention.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 35.96 years STANDARD_DEVIATION 15.61 |
| Body Mass Index | 29.70 kg/m2 STANDARD_DEVIATION 7.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Height | 165.73 cm STANDARD_DEVIATION 3.573 |
| Positive Celiac Serology at Diagnosis DEAMIDATED GLIADIN PEPTIDE IGA (DGP-IGA) | 2 Participants |
| Positive Celiac Serology at Diagnosis DEAMIDATED GLIADIN PEPTIDE IGG (DGP-IGG) | 5 Participants |
| Positive Celiac Serology at Diagnosis TISSUE TRANSGLUTAMINASE IGA ANTIBODY (TTG-IGA) | 119 Participants |
| Positive Celiac Serology at Diagnosis TISSUE TRANSGLUTAMINASE IGG ANTIBODY (TTG-IGG) | 21 Participants |
| Positive Histology at Diagnosis EVIDENCE OF VILLOUS ATROPHY (NO MARSH SCORE REPORTED) | 2 Participants |
| Positive Histology at Diagnosis MARSH SCORE 2 | 0 Participants |
| Positive Histology at Diagnosis MARSH SCORE 3A | 0 Participants |
| Positive Histology at Diagnosis MARSH SCORE 3B | 0 Participants |
| Positive Histology at Diagnosis MARSH SCORE 3C | 2 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized White | 5 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 1 Participants |
| Time on GFD | 7.14 years STANDARD_DEVIATION 5.85 |
| Time since First CeD Diagnosis | 5.5 years STANDARD_DEVIATION 2.76 |
| Weight | 62.00 kg STANDARD_DEVIATION 11.345 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 3 | 0 / 3 | 0 / 5 | 0 / 27 | 0 / 26 | 0 / 26 | 0 / 28 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 4 / 4 | 3 / 3 | 3 / 3 | 5 / 5 | 23 / 27 | 23 / 26 | 24 / 26 | 24 / 28 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 1 / 4 | 1 / 3 | 2 / 3 | 0 / 5 | 0 / 27 | 1 / 26 | 1 / 26 | 0 / 28 |
Outcome results
None listed