Clinical trial NCT04054544: Gluten Challenge Study in Celiac Disease Participants (MK-0000-402)
Official title: A Gluten Challenge Study to Characterize Peripheral Blood and Intestinal Gluten-specific CD4+ T Cell Subsets in Patients With Celiac Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Celiac Disease
Keywords: Celiac disease
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-08-13
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Experimental study to determine blood and duodenal T cell changes following administration of an 8 g gluten challenge daily for 13 days in participants with celiac disease
Primary purpose: BASIC_SCIENCE

Brief summary: This is a gluten challenge study to characterize peripheral blood and intestinal gluten specific cluster of differentiation 4 glycoprotein (CD4+) thymus lymphocyte (T cell) subsets in participants with Celiac Disease

Detailed description: This is a multi-site, open-label gluten challenge study to characterize peripheral blood and intestinal gluten specific CD4+ T cell subsets in participants with celiac disease (CeD). Participants will receive 8 grams (g) of gluten daily for 13 consecutive days. Blood samples will be taken at pre-dose, Day 6, and Day 14. Duodenal biopsy samples will also be collected on Day 14. Participants will also complete a symptom diary.

Eligibility criteria: Inclusion Criteria:

1. Participant must have documented diagnosis with celiac disease (CeD) by duodenal/jejunal biopsy at least 6 months prior to entrance into the study.
2. Participant must be on a gluten-free diet (GFD) for at least the past 12 months.
3. Female participants must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP) must use an acceptable contraceptive method or abstain from heterosexual intercourse.
4. Must be Human leukocyte antigen (HLA)-DQ2.5 positive, assessed at screening. If participants have already been genotyped, results from previous testing may be used in lieu of genotyping at screening.
5. Has anti-tissue transglutaminase (anti-tTG) \<2x upper limit of normal (ULN) as measured by serology.
6. Be judged to be in good health based on medical history, physical examination (including a targeted neurological exam), versus (vs.) measurements and electrocardiogram (ECG) performed prior to treatment allocation.
7. Have a body mass index (BMI) 18-35 kg/m\^2, inclusive.

Exclusion Criteria:

1. Has any chronic active gastrointestinal (GI) disease (e.g., clinically active CeD despite being on GFD for past 12 months, Crohn's disease, ulcerative colitis, lymphocytic colitis). Inactive, stable/well-treated lactose intolerance, Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) intolerance, gastroesophageal reflux disease (GERD), and irritable bowel syndrome (IBS) are allowed.
2. Has clinically active endocrine, gastrointestinal (other than CeD), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. Participants with a remote history of uncomplicated medical events or stable medical diseases with no symptoms and stable treatment for the past \>3 months may be enrolled in the study at the discretion of the investigator.
3. Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder within the last 5 years. Participants who have had situational depression may be enrolled in the study at the discretion of the investigator.
4. Participant has an estimated Glomerular Filtration Rate (eGFR) ≤80 mL/min/1.73 m\^2 at the screening visit based on the Cockcroft-Gault (CG) equation
5. Has a history of significant multiple and/or severe allergies (e.g., food, drug, latex allergy), or has had an anaphylactic reaction or systemic allergic reaction to prescription or nonprescription drugs or food.
6. Subject has a history of severe acute symptomatic reactions to sporadic gluten ingestion.
7. Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV).
8. Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit.
9. Is on Coumadin™ or other anticoagulants.
10. Is unable to refrain from or anticipates the use of systemic anti-inflammatory, immunosuppressive, or immunomodulatory medications, which may include ibuprofen \> 2400 mg/day, naproxen \>750 mg/day, prednisone \>10 mg/day, or methylprednisolone \> 8 mg/day, within 48 hours prior to the start of and throughout the entire gluten challenge.
11. Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit. The window will be derived from the date of the last visit in the previous study.
12. Has a corrected QT (QTc) interval ≥470 msec (for males) or ≥480 msec (for females).

Primary outcomes:
measure: Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
timeFrame: Baseline (Day 1, pre-dose)
measure: Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
timeFrame: Day 14
measure: Percentage of α1-gliadin-reactive CD4+ T Cells in Duodenal Biopsies After Gluten Challenge
timeFrame: Day 14
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital ( Site 0001)
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center ( Site 0002)
state: Massachusetts
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: