Clinical trial NCT04614571: T Cell Receptor (TCR) Sequencing and Transcriptional Profiling in Adult Celiac Disease Patients Undergoing Gluten Challenge
Official title: TCR Sequencing and Transcriptional Profiling in Celiac Disease Patients Undergoing Gluten Challenge
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Celiac Disease
Keywords: CeD
HLA-DQ2 positive
HLA-DQ8 positive
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-11-04
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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


Eligibility 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

Primary outcomes:
measure: Change from Baseline in small intestine TCR repertoire
timeFrame: Up to 30 days post challenge
measure: Change from Baseline in peripheral blood TCR repertoire
timeFrame: Up to 30 days post challenge
measure: Changes from baseline in small intestine and peripheral blood transcriptome
timeFrame: Up to 30 days post challenge
Secondary outcomes:
measure: Change from Baseline in Small Intestine Histology Based on Intraepithelial Lymphocytes (IEL) Count per 100 epithelial cells
timeFrame: Baseline and Day 15
measure: Change from Baseline in Small Intestine Histology Based on Villous Height (Microns), Crypt Depth (Microns) and Villous Height to Crypt Depth Ratio (Vh:Cd)
timeFrame: Baseline and Day 15
measure: Identification and ex vivo functional validation of gluten-specific T cells
timeFrame: Up to 30 days post challenge
Other outcomes:
Locations:
city: Boston
country: United States
facility: Celiac Research Centre Mass General Hospital
state: Massachusetts
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Administrator
role: STUDY_DIRECTOR
References: