Gluten Challenge Study in Celiac Disease Participants (MK-0000-402)

NCT04054544 | Completed Early Phase 1 Results

• 2 other identifiers: 0000-402MK-0000-402
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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

Conditions

Celiac Disease

Keywords

Celiac disease

Outcome Measures

Primary Outcomes (3)

• Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge

  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).

  Baseline (Day 1, pre-dose)

• Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge

  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).

  Day 14

• Percentage of α1-gliadin-reactive CD4+ T Cells in Duodenal Biopsies After Gluten Challenge

  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).

  Day 14

Study Arms (1)

Gluten challenge

EXPERIMENTAL

Participants will receive a gluten 4 g powder twice daily (BID), for 13 consecutive days

Dietary Supplement: Gluten powder 4g

Interventions

Gluten powder 4g DIETARY_SUPPLEMENT

Gluten powder 4g oral BID

Gluten challenge

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must have documented diagnosis with celiac disease (CeD) by duodenal/jejunal biopsy at least 6 months prior to entrance into the study.
• Participant must be on a gluten-free diet (GFD) for at least the past 12 months.
• Female participants must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP) must use an acceptable contraceptive method or abstain from heterosexual intercourse.
• 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.
• Has anti-tissue transglutaminase (anti-tTG) \<2x upper limit of normal (ULN) as measured by serology.
• 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.
• Have a body mass index (BMI) 18-35 kg/m\^2, inclusive.

You may not qualify if:

• 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.
• 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.
• 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.
• 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
• 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.
• Subject has a history of severe acute symptomatic reactions to sporadic gluten ingestion.
• Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV).
• Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit.
• Is on Coumadin™ or other anticoagulants.
• 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.
• 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.
• Has a corrected QT (QTc) interval ≥470 msec (for males) or ≥480 msec (for females).

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (2)

Massachusetts General Hospital ( Site 0001)

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center ( Site 0002)

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Celiac Disease

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

Due to unavailability of appropriate reagents, planned flow cytometry analyses of ω-gliadin reactivity and prevalence of CD95, tumor growth factor β1 receptor (TGFβ1R), and interleukin-27 receptor (IL-27R) antigens could not be performed.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: August 5, 2019
• First Posted: August 13, 2019
• Study Start: August 28, 2020
• Primary Completion: June 23, 2021
• Study Completion: June 23, 2021
• Last Updated: March 6, 2023
• Results First Posted: March 6, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share

Locations

US (2)