Vedolizumab Induction May Prevent Celiac Enteritis

NCT02929316 | Terminated Phase 2 FDA Drug

• 1 other identifier: IISR-2016-101481
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

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)

Conditions

Celiac Disease

Outcome Measures

Primary Outcomes (2)

• Normal histopathology following induction dosing with vedolizumab

  Remission is defined in this study of negative celiac antibodies and normal duodenal biopsies

  12 weeks

• 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

  12 weeks

Study Arms (1)

Vedolizumab

EXPERIMENTAL

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

Drug: Vedolizumab

Interventions

Vedolizumab DRUG

IV infusion week 0, 2 and 6

Also known as: Entyvio

Vedolizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AGA Clinical Research Associates, LLC: lead
• Takeda: collaborator

Study Sites (2)

AGA Clinical Research Associates, LLC

Egg Harbor, New Jersey, 08234, United States

Location

Theresa Stevens

Egg Harbor, New Jersey, 08234, United States

Location

Related Publications (9)

• Green PH, Cellier C. Celiac disease. N Engl J Med. 2007 Oct 25;357(17):1731-43. doi: 10.1056/NEJMra071600. No abstract available.

  PMID: 17960014 RESULT

• 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.

  PMID: 25271602 RESULT

• 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.

  PMID: 12556782 RESULT

• 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.

  PMID: 21131921 RESULT

• 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.

  PMID: 12219789 RESULT

• 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.

  PMID: 12809831 RESULT

• 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.

  PMID: 23163616 RESULT

• 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.

  PMID: 22825365 RESULT

• 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.

  PMID: 22619366 RESULT

MeSH Terms

Conditions

Celiac Disease

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Clinical Research

Study Record Dates

• First Submitted: October 5, 2016
• First Posted: October 11, 2016
• Study Start: June 25, 2018
• Primary Completion: October 5, 2018
• Study Completion: October 5, 2018
• Last Updated: October 10, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)