A Study of Efficacy, Safety, and Tolerability of KAN-101 in People With Celiac Disease

A Phase 2a Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of KAN-101 In Participants With Celiac Disease

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06001177

Acronym

SynCeD

Enrollment

Registered

2023-08-21

Start date

2023-12-13

Completion date

2025-01-13

Last updated

2025-12-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Celiac Disease, Coeliac Disease

Keywords

celiac disease, HLA-DQ2.5, gluten free diet

Brief summary

The study goal is to evaluate the efficacy, safety, and tolerability of KAN-101 in participants with Celiac Disease (CeD)

Detailed description

Study KAN-101-03 is a multi-center, double-blind, placebo-controlled Phase 2a study to examine whether KAN-101 confers protection from gluten exposure induced histological changes in the duodenum and to further evaluate the safety/tolerability of KAN-101 in adult participants (≥18 years) with CeD on a gluten free diet. Approximately 52 participants who meet study inclusion/exclusion criteria will be randomized 1:1 to receive KAN-101 or placebo.

Interventions

DRUGKAN-101

Dose KAN-101 Intravenous (IV) Infusion

DRUGPlacebo

Placebo Intravenous (IV) Infusion

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Masking description

Study participants and their caregivers, investigators and other staff, and sponsor staff involved in the study team will be blinded.

Intervention model description

The study is a randomized, double-blind, placebo-controlled study with approximately 52 participants that will receive KAN-101 or placebo

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

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 * Screening intestinal biopsy demonstrating Vh:Cd ratio of 2.3 or higher

Exclusion criteria

* Refractory celiac disease * HLA-DQ8 genotype * Selective IgA deficiency * Diagnosis of type-I diabetes * Other Active gastrointestinal diseases * History of dermatitis herpetiformis

Design outcomes

Primary

Measure	Time frame	Description
Changes From Baseline in Villous Height to Crypt Depth (Vh:Cd) as Assessed by Esophagogastroduodenoscopy With Biopsy After 2-week Gluten Challenge (GC)	Baseline and Day 29	KAN-101 attenuated GC-induced changes in duodenal histology as measured by the Vh:Cd ratio.

Secondary

Measure	Time frame	Description
Changes From Baseline in Intraepithelial Lymphocyte (IEL) Density in Duodenum Biopsy After 2-week GC	Baseline and Day 29	—
Incidence and Severity of Treatment Emergent Adverse Events (TEAE) as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)	From the time the participant provided informed consent through Day 42.	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. An AE was considered treatment-emergent relative to a given treatment if the event start date is during the on-treatment period (including on the date of first dose).
Incidence by Visit of KAN-101 Antidrug Antibody (ADA)	Up to 42 days	—
KAN-101 Plasma Concentration: AUCinf	0 minutes, 30 minutes, 2 hours 30 minutes, 4 hours post dose on day 1 and day 7	Area under the plasma-concentration time curve from time 0 extrapolated to infinite time.
Change in Magnitude of Interleukin-2 (IL-2) Response From Day 15 (First Day of GC) Pre-GC to Day 15 Post GC	From Day 15 pre-GC to Day 15 post GC	—
KAN-101 Plasma Concentration: Cmax	0 minutes, 30 minutes, 2 hours 30 minutes, 4 hours post dose on day 1 and day 7	Maximum plasma concentration.
KAN-101 Plasma Concentration: Tmax	0 minutes, 30 minutes, 2 hours 30 minutes, 4 hours post dose on day 1 and day 7	Time to reach Cmax.
KAN-101 Plasma Concentration: T1/2	0 minutes, 30 minutes, 2 hours 30 minutes, 4 hours post dose on day 1 and day 7	Terminal phase half-life.
KAN-101 Plasma Concentration: AUClast	0 minutes, 30 minutes, 2 hours 30 minutes, 4 hours post dose on day 1 and day 7	Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (Clast).

Countries

Canada, Finland, Germany, Ireland, Israel, Netherlands, Poland, United States

Participant flow

Recruitment details

A total of 55 participants were enrolled and treated, of which 50 participants completed the study, 2 participants discontinued from the treatment phase, and 3 participants discontinued from the observation phase.

Participants by arm

Arm	Count
0.6 mg/kg KAN-101 All enrolled participants received 0.6 mg/kg of KAN-101 via intravenous (IV) infusions every 3 days starting on Day 1 and ending on Day 7 KAN-101: 0.6 mg/kg KAN-101 Intravenous (IV) Infusion	28
Placebo All enrolled participants received intravenous (IV) infusions of placebo every 3 days starting on Day 1 and ending on Day 7 Placebo: Placebo Intravenous (IV) Infusion	27
Total	55

Withdrawals & dropouts

Period	Reason	FG000	FG001
Observation Phase	Adverse Event	1	1
Observation Phase	Withdrawal by Subject	0	1
Treatment Phase	Adverse Event	1	0
Treatment Phase	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Placebo	Total	0.6 mg/kg KAN-101
Age, Continuous	39.7 years STANDARD_DEVIATION 13.96	39.3 years STANDARD_DEVIATION 14.42	38.9 years STANDARD_DEVIATION 15.1
Body Mass Index	26.07 kg/m2 STANDARD_DEVIATION 5.191	25.68 kg/m2 STANDARD_DEVIATION 5.207	25.30 kg/m2 STANDARD_DEVIATION 5.29
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	3 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants	52 Participants	28 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Height	165.64 cm STANDARD_DEVIATION 8.635	166.72 cm STANDARD_DEVIATION 8.834	167.76 cm STANDARD_DEVIATION 9.055
Human Leukocyte Antigen (HLA) Genotype Negative	0 participants	1 participants	1 participants
Human Leukocyte Antigen (HLA) Genotype Positive	27 participants	54 participants	27 participants
Positive Celiac Serology at Diagnosis DEAMIDATED GLIADIN PEPTIDE IGA (DGP-IGA)	0 participants	3 participants	3 participants
Positive Celiac Serology at Diagnosis DEAMIDATED GLIADIN PEPTIDE IGG (DGP-IGG)	1 participants	5 participants	4 participants
Positive Celiac Serology at Diagnosis TISSUE TRANSGLUTAMINASE IGA ANTIBODY (TTG-IGA)	25 participants	51 participants	26 participants
Positive Celiac Serology at Diagnosis TISSUE TRANSGLUTAMINASE IGG ANTIBODY (TTG-IGG)	1 participants	6 participants	5 participants
Positive Histology at Diagnosis EVIDENCE OF VILLOUS ATROPHY (NO MARSH SCORE REPORTED)	16 participants	34 participants	18 participants
Positive Histology at Diagnosis MARSH SCORE 2	3 participants	3 participants	0 participants
Positive Histology at Diagnosis MARSH SCORE 3A	1 participants	5 participants	4 participants
Positive Histology at Diagnosis MARSH SCORE 3B	5 participants	8 participants	3 participants
Positive Histology at Diagnosis MARSH SCORE 3C	2 participants	5 participants	3 participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	27 Participants	55 Participants	28 Participants
Sex: Female, Male Female	25 Participants	46 Participants	21 Participants
Sex: Female, Male Male	2 Participants	9 Participants	7 Participants
Time on Gluten-Free Diet (GFD)	7.5 years STANDARD_DEVIATION 5.66	7.5 years STANDARD_DEVIATION 5.45	7.4 years STANDARD_DEVIATION 5.34
Time since First CeD Diagnosis	9.4 years STANDARD_DEVIATION 5.57	8.6 years STANDARD_DEVIATION 5.48	7.8 years STANDARD_DEVIATION 5.36
Weight	71.23 kg STANDARD_DEVIATION 13.386	71.26 kg STANDARD_DEVIATION 14.738	71.30 kg STANDARD_DEVIATION 16.183

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 28	0 / 27
other Total, other adverse events	24 / 28	20 / 27
serious Total, serious adverse events	1 / 28	0 / 27

Outcome results

Primary

Changes From Baseline in Villous Height to Crypt Depth (Vh:Cd) as Assessed by Esophagogastroduodenoscopy With Biopsy After 2-week Gluten Challenge (GC)

KAN-101 attenuated GC-induced changes in duodenal histology as measured by the Vh:Cd ratio.

Time frame: Baseline and Day 29

Population: Full Analysis Set - All participants who were randomly assigned to the study intervention, received all 3 doses of the study intervention, and completed at least 7 days of the 2-week GC without prohibited medications. Participants were analyzed according to the study intervention they were randomized.

Arm	Measure	Value (MEAN)	Dispersion
0.6 mg/kg KAN-101	Changes From Baseline in Villous Height to Crypt Depth (Vh:Cd) as Assessed by Esophagogastroduodenoscopy With Biopsy After 2-week Gluten Challenge (GC)	-0.85 ratio	Standard Deviation 0.707
Placebo	Changes From Baseline in Villous Height to Crypt Depth (Vh:Cd) as Assessed by Esophagogastroduodenoscopy With Biopsy After 2-week Gluten Challenge (GC)	-0.61 ratio	Standard Deviation 0.614

p-value: 0.166895% CI: [-0.63, 0.11]ANCOVA

Secondary

Change in Magnitude of Interleukin-2 (IL-2) Response From Day 15 (First Day of GC) Pre-GC to Day 15 Post GC

Time frame: From Day 15 pre-GC to Day 15 post GC

Population: Biomarker Analysis Set - All participants who were randomly assigned to the study intervention, received any portion of the study intervention, and had completed the GC on Day 15 without prohibited medications. Participants were analyzed according to the study intervention they were randomized.

Arm	Measure	Value (MEAN)	Dispersion
0.6 mg/kg KAN-101	Change in Magnitude of Interleukin-2 (IL-2) Response From Day 15 (First Day of GC) Pre-GC to Day 15 Post GC	31.8 international unit	Standard Deviation 95.86
Placebo	Change in Magnitude of Interleukin-2 (IL-2) Response From Day 15 (First Day of GC) Pre-GC to Day 15 Post GC	31.1 international unit	Standard Deviation 102.3

Secondary

Changes From Baseline in Intraepithelial Lymphocyte (IEL) Density in Duodenum Biopsy After 2-week GC

Time frame: Baseline and Day 29

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
0.6 mg/kg KAN-101	Changes From Baseline in Intraepithelial Lymphocyte (IEL) Density in Duodenum Biopsy After 2-week GC	20.68 cells per 100 epithelial cells	Standard Deviation 17.447
Placebo	Changes From Baseline in Intraepithelial Lymphocyte (IEL) Density in Duodenum Biopsy After 2-week GC	17.36 cells per 100 epithelial cells	Standard Deviation 16.286

Secondary

Incidence and Severity of Treatment Emergent Adverse Events (TEAE) as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)

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. An AE was considered treatment-emergent relative to a given treatment if the event start date is during the on-treatment period (including on the date of first dose).

Time frame: From the time the participant provided informed consent through Day 42.

Population: Safety Analysis Set - All participants who received any portion of the study intervention. Participants were analyzed according to the study intervention they actually received.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
0.6 mg/kg KAN-101	Incidence and Severity of Treatment Emergent Adverse Events (TEAE) as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)	Grade 2 TEAE	0 Participants
0.6 mg/kg KAN-101	Incidence and Severity of Treatment Emergent Adverse Events (TEAE) as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)	TEAE	25 Participants
0.6 mg/kg KAN-101	Incidence and Severity of Treatment Emergent Adverse Events (TEAE) as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)	Grade 3 or higher TEAE	1 Participants
0.6 mg/kg KAN-101	Incidence and Severity of Treatment Emergent Adverse Events (TEAE) as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)	SAE	1 Participants
Placebo	Incidence and Severity of Treatment Emergent Adverse Events (TEAE) as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)	Grade 3 or higher TEAE	0 Participants
Placebo	Incidence and Severity of Treatment Emergent Adverse Events (TEAE) as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)	TEAE	22 Participants
Placebo	Incidence and Severity of Treatment Emergent Adverse Events (TEAE) as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)	Grade 2 TEAE	1 Participants
Placebo	Incidence and Severity of Treatment Emergent Adverse Events (TEAE) as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)	SAE	0 Participants

Secondary

Incidence by Visit of KAN-101 Antidrug Antibody (ADA)

Time frame: Up to 42 days

Population: Safety analysis set - all participants who received any portion of study intervention. Participants with at least 1 positive response post-treatment.

Arm	Measure	Group	Value (NUMBER)
0.6 mg/kg KAN-101	Incidence by Visit of KAN-101 Antidrug Antibody (ADA)	Baseline	0 participants
0.6 mg/kg KAN-101	Incidence by Visit of KAN-101 Antidrug Antibody (ADA)	Day 7	0 participants
0.6 mg/kg KAN-101	Incidence by Visit of KAN-101 Antidrug Antibody (ADA)	Day 29	3 participants
0.6 mg/kg KAN-101	Incidence by Visit of KAN-101 Antidrug Antibody (ADA)	Day 42	5 participants

Secondary