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Vedolizumab Induction May Prevent Celiac Enteritis

Primary Purpose

Celiac Disease

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Vedolizumab
Sponsored by
AGA Clinical Research Associates, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Celiac Disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • AGA Clinical Research Associates, LLC
  • Theresa Stevens

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vedolizumab

Arm Description

Vedolizumab (Entyvio) 300mg IV at week 0, 2 and 6

Outcomes

Primary Outcome Measures

Normal histopathology following induction dosing with vedolizumab
Remission is defined in this study of negative celiac antibodies and normal duodenal biopsies
Normal histopathology following induction dosing with vedolizumab after 2 week gluten challange
Remission is defined in this study as negative celiac antibodies and normal duodenal biopsies

Secondary Outcome Measures

Full Information

First Posted
October 5, 2016
Last Updated
October 8, 2018
Sponsor
AGA Clinical Research Associates, LLC
Collaborators
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT02929316
Brief Title
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

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Terminated
Why Stopped
Lack of enrollment
Study Start Date
June 25, 2018 (Actual)
Primary Completion Date
October 5, 2018 (Actual)
Study Completion Date
October 5, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
AGA Clinical Research Associates, LLC
Collaborators
Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Celiac Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vedolizumab
Arm Type
Experimental
Arm Description
Vedolizumab (Entyvio) 300mg IV at week 0, 2 and 6
Intervention Type
Drug
Intervention Name(s)
Vedolizumab
Other Intervention Name(s)
Entyvio
Intervention Description
IV infusion week 0, 2 and 6
Primary Outcome Measure Information:
Title
Normal histopathology following induction dosing with vedolizumab
Description
Remission is defined in this study of negative celiac antibodies and normal duodenal biopsies
Time Frame
12 weeks
Title
Normal histopathology following induction dosing with vedolizumab after 2 week gluten challange
Description
Remission is defined in this study as negative celiac antibodies and normal duodenal biopsies
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Facility Information:
Facility Name
AGA Clinical Research Associates, LLC
City
Egg Harbor Township
State/Province
New Jersey
ZIP/Postal Code
08234
Country
United States
Facility Name
Theresa Stevens
City
Egg Harbor Township
State/Province
New Jersey
ZIP/Postal Code
08234
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
17960014
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.
Results Reference
result
PubMed Identifier
25271602
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.
Results Reference
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PubMed Identifier
12556782
Citation
Lee SK, Lo W, Memeo L, Rotterdam H, Green PH. Duodenal histology in patients with celiac disease after treatment with a gluten-free diet. Gastrointest Endosc. 2003 Feb;57(2):187-91. doi: 10.1067/mge.2003.54.
Results Reference
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PubMed Identifier
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Citation
Leffler DA, Schuppan D. Update on serologic testing in celiac disease. Am J Gastroenterol. 2010 Dec;105(12):2520-4. doi: 10.1038/ajg.2010.276.
Results Reference
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PubMed Identifier
12219789
Citation
Wahab PJ, Meijer JW, Mulder CJ. Histologic follow-up of people with celiac disease on a gluten-free diet: slow and incomplete recovery. Am J Clin Pathol. 2002 Sep;118(3):459-63. doi: 10.1309/EVXT-851X-WHLC-RLX9.
Results Reference
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PubMed Identifier
12809831
Citation
Vahedi K, Mascart F, Mary JY, Laberenne JE, Bouhnik Y, Morin MC, Ocmant A, Velly C, Colombel JF, Matuchansky C. Reliability of antitransglutaminase antibodies as predictors of gluten-free diet compliance in adult celiac disease. Am J Gastroenterol. 2003 May;98(5):1079-87. doi: 10.1111/j.1572-0241.2003.07284.x.
Results Reference
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PubMed Identifier
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Citation
Kelly CP, Green PH, Murray JA, Dimarino A, Colatrella A, Leffler DA, Alexander T, Arsenescu R, Leon F, Jiang JG, Arterburn LA, Paterson BM, Fedorak RN; Larazotide Acetate Celiac Disease Study Group. Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Aliment Pharmacol Ther. 2013 Jan;37(2):252-62. doi: 10.1111/apt.12147. Epub 2012 Nov 19.
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Citation
Leffler DA, Kelly CP, Abdallah HZ, Colatrella AM, Harris LA, Leon F, Arterburn LA, Paterson BM, Lan ZH, Murray JA. A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterol. 2012 Oct;107(10):1554-62. doi: 10.1038/ajg.2012.211. Epub 2012 Jul 24.
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Citation
Leffler D, Schuppan D, Pallav K, Najarian R, Goldsmith JD, Hansen J, Kabbani T, Dennis M, Kelly CP. Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease. Gut. 2013 Jul;62(7):996-1004. doi: 10.1136/gutjnl-2012-302196. Epub 2012 May 22.
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Vedolizumab Induction May Prevent Celiac Enteritis

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