A Study to Evaluate Gluten Challenge on Immune Responses in Subjects With Celiac Disease

Model Development, Clinical Study to Evaluate Gluten Challenge on Immune Responses in Subjects With Celiac Disease.

This is a model development, open label, no therapeutic treatment, three sequential group, short term-gluten challenge study in subjects with celiac disease. Immune responses are evaluated following gluten challenge.

Approximately fifteen subjects with celiac disease will be enrolled in up to three sequential groups (5 subjects per group).

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

1. Male and female subjects of any race between 18 to 65 years of age (inclusive) at the time of signing the informed consent form (ICF).

2. Must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.

3. Must be able to communicate with the investigator, understand and comply with the requirements of the study, and agree to adhere to restrictions and examination schedules.

4. Documented diagnosis of celiac disease ≥ 6 months before study entry, based on American College of Gastroenterology 2013 guideline on celiac disease diagnosis and management. The confirmation of a diagnosis of CD should be based on a combination of findings from the medical history, physical examination, serology, and upper endoscopy with histological analysis of multiple biopsies of the duodenum.

   1. A positive biopsy consistent with celiac disease. Every effort should be made to obtain the biopsy report to support the diagnosis of CD. Prospective subjects should not undergo biopsy for the sole purpose for participating in this trial. And
   2. A documented positive gluten-specific serology to tissue transglutaminase (tTG), endomysial antibodies (EMA), and/or gliadin-derived peptides (GDP).

5. Group 1 subjects must have been following a gluten-free diet for ≥ 6 months before study entry and have been in remission based on self-reporting and must have negative IgA antibodies to tTG at screening. For Group 2 and 3 the gluten free diet duration may be reduced to a minimum of 3 months. Notification of the changes for Group 2 and 3 will be provided to the site(s).

6. Subjects must have HLA DQ2.5 (i.e., DQA1*05/DQB1*02).

7. No clinically significant abnormal laboratory test results other than those related to celiac disease as determined by the investigator.

8. At the screening visit, must be afebrile, with supine systolic BP: 90 to 140 mmHg, supine diastolic BP: 50 to 90 mmHg, and pulse rate: 40 to 110 bpm. Eligibility criteria for vital signs performed on Day 0 (or Day 1 pre-gluten challenge) will be at the discretion of the Investigator. In the opinion of the Investigator, subjects with hypertension controlled with a concomitant medication will be allowed in the study.

9. Must have a normal or clinically acceptable 12-lead ECG.

10. Female subject must have a negative pregnancy test at screening and on Day 0 (or Day 1 pre-gluten challenge).

11. Subject must be willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Any significant medical condition, laboratory abnormality, or psychiatric illness, Type 1 diabetes, other than celiac disease, that would prevent the subject from participating in the study.
2. Any condition which places the subject at unacceptable risk if he were to participate in the study, or confounds the ability to interpret data from the study.
3. Use of any prescribed systemic immune modulator medication within 30 days of the first bread administration.
4. The use of prescribed and over-the-counter non-steroidal anti-inflammatory drugs (NSAID) within 14 days of the first bread administration.
5. Exposure to an investigational drug (new chemical entity) within 30 days prior to the first bread administration or 5 half-lives of that investigational drug, if known (whichever is longer).
6. Donated blood or plasma within 8 weeks before the first bread administration to a blood bank or blood donation center.
7. History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual [DSM]) within 2 years before dosing, or a positive drug screen reflecting consumption of illicit drugs. For states in which marijuana is legal; prior use of marijuana may be acceptable as long as the screening drug screen is negative. Subjects may be re-screened in case the drug screen tests positive for marijuana. Subjects must refrain from the use of marijuana 2 weeks prior to screening until the end of study.
8. History of alcohol abuse (as defined by the current version of the DSM) within 2 years before screening, or a positive alcohol screen.
9. Known to have hepatitis, or known to be a carrier of the hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV Ab), or have a positive result to the test for human immunodeficiency virus (HIV) antibodies at screening.
10. Any condition that confounds the ability to interpret data from the study.
11. Subjects with a history of hypersensitivity or anaphylaxis to gluten.