Clinical trial NCT02929316: Vedolizumab Induction May Prevent Celiac Enteritis
Official title: Vedolizumab Induction May Prevent Celiac Enteritis After Gluten Challenge in Established Celiac Patients in Histological Remission
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Celiac Disease
Lead sponsor: AGA Clinical Research Associates, LLC
Sponsor class: OTHER
Collaborators: name: Takeda
First posted: 2016-10-11
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Celiac disease (CD) is characterized as an autoimmune disorder whereby gluten (a protein found in wheat, barley, rye, malt) induces an immunological response in genetically susceptible individuals. The prevalence of CD has been estimated to affect 0.5-1% of the population worldwide. Long term sequelae are numerous and include risk of lymphoma, malabsorption leading to weight loss, anemia, multiple vitamin deficiencies, osteoporosis/osteopenia, secondary autoimmunity, etc. (1)

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Normal histopathology following induction dosing with vedolizumab
timeFrame: 12 weeks
measure: Normal histopathology following induction dosing with vedolizumab after 2 week gluten challange
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Egg Harbor Township
country: United States
facility: AGA Clinical Research Associates, LLC
state: New Jersey
city: Egg Harbor Township
country: United States
facility: Theresa Stevens
state: New Jersey
Study officials:
References:
citation: Green PH, Cellier C. Celiac disease. N Engl J Med. 2007 Oct 25;357(17):1731-43. doi: 10.1056/NEJMra071600. No abstract available.
citation: Lionetti E, Castellaneta S, Francavilla R, Pulvirenti A, Tonutti E, Amarri S, Barbato M, Barbera C, Barera G, Bellantoni A, Castellano E, Guariso G, Limongelli MG, Pellegrino S, Polloni C, Ughi C, Zuin G, Fasano A, Catassi C; SIGENP (Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition) Working Group on Weaning and CD Risk. Introduction of gluten, HLA status, and the risk of celiac disease in children. N Engl J Med. 2014 Oct 2;371(14):1295-303. doi: 10.1056/NEJMoa1400697.
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