Vedolizumab Induction May Prevent Celiac Enteritis

Adult subjects with CD will be recruited through our clinic. All patients enrolled will have
established CD diagnosed > 6 months. All patients will have history of abnormal MARSH score
on initial duodenal biopsy at diagnosis and MARSH 0 on repeat biopsy following a gluten free
diet (GFD). All patients will also have positive celiac serologies (anti-TTG, anti-gliadin,
etc.) at diagnosis, as well as, positive HLA DQ2/DQ8 genetic profile. At enrollment, all
patients will have negative celiac serologies, indicative of serologic remission on a gluten
free diet. Female subjects of childbearing potential (does not include those with history of
tubal ligation/surgical sterilization, hysterectomy and/or oophorectomy) who are sexually
active with a non-sterilized male partners agree to routinely use adequate contraception from
signing informed consent, during study process and for an additional 18 weeks after the last
dose of vedolizumab. A male subject who is non-sterilized and sexually active with a female
partner of childbearing potential agrees to use adequate contraception from signing informed
consent throughout the duration of the study and for 18 weeks after the last dose.

Inclusion Criteria:

- Patients must meet the following criteria for study entry:

- Adult patients with Celiac Disease (CD)

- Without any additional co-morbidities

- Normal renal and hepatic function

- Diagnosis of CD established at least 6 months prior to trial with diagnostic serology,
genetic profile, endoscopic appearance and histopathology report In histologic and
serologic remission (defined as MARSH 0 and negative anti-tissue transglutaminase,
etc.) following a gluten free diet

- Naïve to treatment with vedolizumab

- Able and willing to provide written informed consent

- Eligibility criteria for laboratory profiles - healthy patient normal laboratory
reference values

- WBC 4.5-12.0 k/UL

- Platelet count- 140-415 k/UL

- Hemoglobin- 11.0-17.4 %g/dL

- Renal Function-

- Creatinine- 0.5-1.3 mg/dL

- BUN- 5-20 mg/dL

- Hepatic Function

- Albumin - 3.3-5.0 g/dL

- INR- 0.9-1.1

- AST- 0-37 U/L

- ALT- 0-40 U/L

- Total Bilirubin- 0.1-1.3 mg/dL

- Alk Phos- 35-150 U/L

Exclusion Criteria:

- Patients who meet any of the following criteria will be excluded from study entry:

- Abnormal MARSH score on enrollment histopathology

- Elevated celiac serologies (anti-tissue transglutaminase, etc.)

- Current use of biologics or immunomodulators Adalimumab, infliximab, Ustekinumab,
Golimumab, Tocilizumab, Certolizumab, Etanercept, Rituximab, Anakinra, Abatacept,
Tofacitinib, Methotrexate, Azathioprine, 6-MP.

- Current use of immunosuppressive therapy including intermittent systemic
corticosteroids within two months of vedolizumab induction

- History of intestinal lymphoma (MALToma, etc.)

- History of cancer including hematologic malignancy, solid tumors, carcinoma in situ,
etc.

- Pregnant or lactating

- Fertile females will require at least one form of birth control

- Lack of peripheral venous access

- Inability to comply with study protocol, in the opinion of the investigator

- Neurological conditions which may interfere with monitoring for PML

- History of demyelinating disease or history of major neurological disease

- History of alcohol, drug or chemical abuse < 6 months prior to screening

- History of active tuberculosis (TB) or a positive screening test for latent
mycobacterium tuberculosis infection

- Positive PPD= > 10 mm or > 5mm in patients on 15 mg or more of prednisone

- History of BCG vaccination should be screened using Quantiferon TB Gold test

- An Indeterminate Quantiferon test will require a chest X-ray to rule out active TB and
consultation with an infectious disease specialist to confirm the risk of latent

- TB is low and that patients can be safely enrolled in the trial

- History of recurrent opportunistic infections and/or of severe or disseminated viral
infections

- Active autoimmune disease

- Active inflammatory bowel disease