T Cell Receptor (TCR) Sequencing and Transcriptional Profiling in Adult Celiac Disease Patients Undergoing Gluten Challenge

Regeneron Pharmaceuticals

Status: Completed

Conditions: Celiac Disease

Treatments: Dietary Supplement: Gluten Powder

Study type: Interventional

Funder types: Industry

Identifiers

NCT04614571

0000-CD-CES-1880

Details and patient eligibility

About

The primary objectives are:

• Characterize the T cell receptor (TCR) repertoire in duodenal biopsy samples of participants pre- and post-challenge.
• Compare for each patient the TCR repertoire of duodenal biopsy samples with the peripheral blood TCR repertoire of each study participant
• Characterize the transcriptome of duodenal biopsy samples and blood from study participants pre- and post-challenge

The secondary objectives are:

• Ex vivo identification and validation of DQ-restricted gliadin specific TCRs.
• Characterize the gluten-challenge induced changes in small intestine histology using standard for Celiac Disease (CeD) histological assessments

Enrollment: 24 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Have a body mass index (BMI) ≥17 and ≤40 kg/m2 and a body weight >45 kg at the Screening Visit
2. Be judged to be in good health as defined in the protocol
3. Have well-controlled biopsy-proven CeD, compliant with a GFD for ≥6 months preceding Screening as defined in the protocol
4. Be HLA-DQ2 and/or HLA-DQ8 positive as defined in the protocol

Key Exclusion Criteria:

1. Have a history of gluten triggered acute symptoms (≤24 hours after gluten exposure), and/or severe symptoms (abdominal pain interfering with daily activities, diarrhea with >5 stools/day), and/or prolonged symptoms (duration >7 days)
2. Have a history of clinically significant endocrine, cardiovascular, hematological, hepatic, immunological (other than CeD or autoimmune thyroid disease), renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or disease
3. Have participated in another investigational trial within 4 weeks before Screening
4. Have a history of cancer (malignancy) other than nonmelanoma skin cancer
5. Have a history of significant multiple and/or severe allergies (e.g., latex allergy)
6. Presence of HIV (HIV Ab), hepatitis B (HBsAg, HBAb) or Hepatitis C (HCV Ab) seropositivity at screening
7. Ongoing immunosuppression or receive any treatment that might alter T cell repertoire or phenotype

Note: Other protocol-defined inclusion/ exclusion criteria apply

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 1 patient group

Gluten Challenge

Other group

Treatment:

Dietary Supplement: Gluten Powder