Trial Outcomes & Findings for Gluten Challenge Study in Celiac Disease Participants (MK-0000-402) (NCT NCT04054544)
NCT ID: NCT04054544
Last Updated: 2023-03-06
Results Overview
Peripheral blood mononuclear cells (PBMC) collected prior to gluten challenge were stained with phycoerythrin (PE)-labeled human leukocyte antigen (HLA)-DQ2.5: gluten tetramers (DQ2.5-glia-α1 and DQ2.5-glia-α2) to identify antigen-specific cluster of differentiation (CD)4-positive thymus lymphocyte (T cells) reactive to gliadin (tetramer+ T cells) by flow cytometry. PBMC were also labeled with a 20-antibody panel for cell surface antigen staining to further define tetramer+ T cell subsets. Antigens included in the analysis were CD25, CD38, CD39, programmed cell death receptor 1 (PD-1), and integrin beta-7 (B7).
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
18 participants
Primary outcome timeframe
Baseline (Day 1, pre-dose)
Results posted on
2023-03-06
Participant Flow
Participant milestones
| Measure |
Gluten Challenge
Participants with celiac disease received 8 g gluten powder (4 g twice daily) orally for 13 consecutive days.
|
|---|---|
|
Overall Study
STARTED
|
18
|
|
Overall Study
COMPLETED
|
18
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Gluten Challenge Study in Celiac Disease Participants (MK-0000-402)
Baseline characteristics by cohort
| Measure |
Gluten Challenge
n=18 Participants
Participants with celiac disease received 8 g gluten powder (4 g twice daily) orally for 13 consecutive days.
|
|---|---|
|
Age, Continuous
|
35.9 Years
STANDARD_DEVIATION 15.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 1, pre-dose)Population: The analysis population includes participants who were compliant with study procedures and had available data.
Peripheral blood mononuclear cells (PBMC) collected prior to gluten challenge were stained with phycoerythrin (PE)-labeled human leukocyte antigen (HLA)-DQ2.5: gluten tetramers (DQ2.5-glia-α1 and DQ2.5-glia-α2) to identify antigen-specific cluster of differentiation (CD)4-positive thymus lymphocyte (T cells) reactive to gliadin (tetramer+ T cells) by flow cytometry. PBMC were also labeled with a 20-antibody panel for cell surface antigen staining to further define tetramer+ T cell subsets. Antigens included in the analysis were CD25, CD38, CD39, programmed cell death receptor 1 (PD-1), and integrin beta-7 (B7).
Outcome measures
| Measure |
Gluten Challenge
n=15 Participants
Participants with celiac disease received 8 g gluten powder (4 g twice daily) orally for 13 consecutive days.
|
|---|---|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
α1-gliadin tetramer+
|
0.00364 Percentage of T cells
Standard Deviation 0.00278
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
α1-gliadin tetramer+, CD25+
|
0.00016 Percentage of T cells
Standard Deviation 0.00029
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
α1-gliadin tetramer+, CD38+
|
0.00049 Percentage of T cells
Standard Deviation 0.00080
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
α1-gliadin tetramer+, CD39+
|
0.00005 Percentage of T cells
Standard Deviation 0.00021
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
α1-gliadin tetramer+, PD1+
|
0.00007 Percentage of T cells
Standard Deviation 0.00020
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
α1-gliadin tetramer+, Integrin B7+
|
0.00161 Percentage of T cells
Standard Deviation 0.00162
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
α2-gliadin tetramer+
|
0.01115 Percentage of T cells
Standard Deviation 0.00988
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
α2-gliadin tetramer+, CD25+
|
0.00058 Percentage of T cells
Standard Deviation 0.00092
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
α2-gliadin tetramer+, CD38+
|
0.00080 Percentage of T cells
Standard Deviation 0.00151
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
α2-gliadin tetramer+, CD39+
|
0.00006 Percentage of T cells
Standard Deviation 0.00024
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
α2-gliadin tetramer+, PD1+
|
0.00010 Percentage of T cells
Standard Deviation 0.00037
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
α2-gliadin tetramer+, Integrin B7+
|
0.00335 Percentage of T cells
Standard Deviation 0.00423
|
PRIMARY outcome
Timeframe: Day 14Population: The analysis population includes participants who were compliant with study procedures and had available data.
Peripheral blood mononuclear cells (PBMC) collected on Day 14 following gluten challenge were stained with phycoerythrin (PE)-labeled human leukocyte antigen (HLA)-DQ2.5: gluten tetramers (DQ2.5-glia-α1 and DQ2.5-glia-α2) to identify antigen-specific cluster of differentiation (CD)4-positive thymus lymphocyte (T cells) reactive to gliadin (tetramer+ T cells) by flow cytometry. PBMC were also labeled with a 20-antibody panel for cell surface antigen staining to further define tetramer+ T cell subsets. Antigens included in the analysis were CD25, CD38, CD39, programmed cell death receptor 1 (PD-1), and integrin beta-7 (B7).
Outcome measures
| Measure |
Gluten Challenge
n=15 Participants
Participants with celiac disease received 8 g gluten powder (4 g twice daily) orally for 13 consecutive days.
|
|---|---|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
α1-gliadin tetramer+, PD1+
|
0.00091 Percentage of T cells
Standard Deviation 0.00113
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
α1-gliadin tetramer+, Integrin B7+
|
0.00361 Percentage of T cells
Standard Deviation 0.00198
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
α1-gliadin tetramer+
|
0.00707 Percentage of T cells
Standard Deviation 0.00510
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
α1-gliadin tetramer+, CD25+
|
0.00054 Percentage of T cells
Standard Deviation 0.00071
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
α1-gliadin tetramer+, CD38+
|
0.00276 Percentage of T cells
Standard Deviation 0.00161
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
α1-gliadin tetramer+, CD39+
|
0.00049 Percentage of T cells
Standard Deviation 0.00075
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
α2-gliadin tetramer+
|
0.01315 Percentage of T cells
Standard Deviation 0.01199
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
α2-gliadin tetramer+, CD25+
|
0.00177 Percentage of T cells
Standard Deviation 0.00391
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
α2-gliadin tetramer+, CD38+
|
0.00495 Percentage of T cells
Standard Deviation 0.00698
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
α2-gliadin tetramer+, CD39+
|
0.00018 Percentage of T cells
Standard Deviation 0.00070
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
α2-gliadin tetramer+, PD1+
|
0.00186 Percentage of T cells
Standard Deviation 0.00378
|
|
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
α2-gliadin tetramer+, Integrin B7+
|
0.00609 Percentage of T cells
Standard Deviation 0.00470
|
PRIMARY outcome
Timeframe: Day 14Population: The analysis population includes participants who were compliant with study procedures and had available data.
Lymphocytes from duodenal biopsies collected on Day 14 following gluten challenge were stained with a phycoerythrin (PE)-labeled human leukocyte antigen (HLA)-DQ2.5: gluten tetramer (DQ2.5-glia-α1) to identify antigen-specific cluster of differentiation (CD)4-positive thymus lymphocyte (T cells) reactive to gliadin (tetramer+ T cells) by flow cytometry. Lymphocytes were also labeled with a 20-antibody panel for cell surface antigen staining to further define tetramer+ T cell subsets. Antigens included in the analysis were CD25, CD38, CD39, programmed cell death receptor 1 (PD-1), and integrin beta-7 (B7).
Outcome measures
| Measure |
Gluten Challenge
n=15 Participants
Participants with celiac disease received 8 g gluten powder (4 g twice daily) orally for 13 consecutive days.
|
|---|---|
|
Percentage of α1-gliadin-reactive CD4+ T Cells in Duodenal Biopsies After Gluten Challenge
α1-gliadin tetramer+
|
0.29347 Percentage of T cells
Standard Deviation 0.26689
|
|
Percentage of α1-gliadin-reactive CD4+ T Cells in Duodenal Biopsies After Gluten Challenge
α1-gliadin tetramer+, CD25+
|
0.00263 Percentage of T cells
Standard Deviation 0.00401
|
|
Percentage of α1-gliadin-reactive CD4+ T Cells in Duodenal Biopsies After Gluten Challenge
α1-gliadin tetramer+, CD38+
|
0.19977 Percentage of T cells
Standard Deviation 0.19001
|
|
Percentage of α1-gliadin-reactive CD4+ T Cells in Duodenal Biopsies After Gluten Challenge
α1-gliadin tetramer+, CD39+
|
0.21248 Percentage of T cells
Standard Deviation 0.24696
|
|
Percentage of α1-gliadin-reactive CD4+ T Cells in Duodenal Biopsies After Gluten Challenge
α1-gliadin tetramer+, PD1+
|
0.26563 Percentage of T cells
Standard Deviation 0.26510
|
|
Percentage of α1-gliadin-reactive CD4+ T Cells in Duodenal Biopsies After Gluten Challenge
α1-gliadin tetramer+, Integrin B7+
|
0.24281 Percentage of T cells
Standard Deviation 0.24192
|
Adverse Events
Gluten Challenge
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Gluten Challenge
n=18 participants at risk
Participants with celiac disease received 8 g gluten powder (4 g twice daily) orally for 13 consecutive days.
|
|---|---|
|
Cardiac disorders
Palpitations
|
5.6%
1/18 • Number of events 1 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Gastrointestinal disorders
Abdominal distension
|
55.6%
10/18 • Number of events 13 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
3/18 • Number of events 3 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Gastrointestinal disorders
Aphthous ulcer
|
5.6%
1/18 • Number of events 1 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Gastrointestinal disorders
Diarrhoea
|
27.8%
5/18 • Number of events 6 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Gastrointestinal disorders
Dyspepsia
|
11.1%
2/18 • Number of events 2 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Gastrointestinal disorders
Epigastric discomfort
|
5.6%
1/18 • Number of events 1 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.6%
1/18 • Number of events 1 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Gastrointestinal disorders
Mucous stools
|
5.6%
1/18 • Number of events 1 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Gastrointestinal disorders
Nausea
|
55.6%
10/18 • Number of events 11 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Gastrointestinal disorders
Rectal tenesmus
|
5.6%
1/18 • Number of events 1 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Gastrointestinal disorders
Vomiting
|
27.8%
5/18 • Number of events 5 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
General disorders
Asthenia
|
5.6%
1/18 • Number of events 1 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
General disorders
Fatigue
|
50.0%
9/18 • Number of events 10 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
General disorders
Feeling abnormal
|
22.2%
4/18 • Number of events 4 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Metabolism and nutrition disorders
Increased appetite
|
5.6%
1/18 • Number of events 1 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.6%
1/18 • Number of events 1 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Nervous system disorders
Balance disorder
|
5.6%
1/18 • Number of events 1 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Nervous system disorders
Dizziness
|
5.6%
1/18 • Number of events 1 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Nervous system disorders
Headache
|
33.3%
6/18 • Number of events 6 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Psychiatric disorders
Insomnia
|
5.6%
1/18 • Number of events 1 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.6%
1/18 • Number of events 1 • Up to 27 days
All-cause mortality was analyzed in all randomized participants; Adverse events were analyzed in all randomized participants who received gluten challenge for at least one day.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme LLC
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor will generally support publication of multicenter studies only in their entirety and not as individual site data. In this case, a coordinating investigator will be designated by mutual agreement. If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
- Publication restrictions are in place
Restriction type: OTHER