The Impact of Anti-TNF Exposure on Vedolizumab Effectiveness

NCT02423512 | Completed DMC

• 2 other identifiers: GCO 15-0651IISR-2015-100947
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Vedolizumab is a new medication being used for the treatment of Crohn's disease and Ulcerative colitis. It works by blocking specific white blood cells (alpha 4-beta7 lymphocytes) from migrating to areas of inflammation in the gastrointestinal tract. Previous studies have shown that patients who have previous exposure to another type of medication for Crohn's disease and Ulcerative colitis (anti-TNF medications) do not respond to vedolizumab as well as those who have never been exposed. This study will investigate biologic markers in the blood and tissue the help identify possible reasons for this difference.

Conditions

Inflammatory Bowel Disease; Crohn's Disease; Ulcerative Colitis

Keywords

Inflammatory Bowel Diseases; Vedolizumab; Ulcerative Colitis; Crohn's Disease; MADCAM1; integrin alpha4beta7

Outcome Measures

Primary Outcomes (1)

• biomarker MAdCAM-1

  change in biomarker MAdCAM-1 at week 14 as compared to baseline

  baseline and week 14

Secondary Outcomes (6)

• biomarker alpha 4 beta 7

  baseline and week 14

• TNF levels

  baseline and week 14

• mucosal drug concentration

  week 14

• mucosal drug concentration

  week 30

• vedolizumab drug concentration

  week 14

Study Arms (2)

Anti-TNF Exposure

Inflammatory Bowel Disease (IBD) patients scheduled to start vedolizumab therapy who have been previously exposed to anti-TNF therapy

anti-TNF Naive

IBD patients scheduled to start vedolizumab therapy who have not been previously exposed to anti-TNF therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Male and female adults with a diagnosis of inflammatory bowel disease who will be started on vedolizumab therapy as clinically indicated and in discussion with their treating physician will be eligible. Patients will not be started on vedolizumab for the sole purpose of this study

You may qualify if:

• Male and female adults with a diagnosis of inflammatory bowel disease
• Patients who will be started on vedolizumab therapy as clinically indicated and in discussion with their treating physician will be eligible. Patients will not be started on vedolizumab for the sole purpose of this study

You may not qualify if:

• Patients with prior exposure to vedolizumab or natalizumab

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Susan and Leonard Feinstein Inflammatory Bowel Disease Center

New York, New York, 10029, United States

Location

Related Publications (5)

• Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, Lukas M, Fedorak RN, Lee S, Bressler B, Fox I, Rosario M, Sankoh S, Xu J, Stephens K, Milch C, Parikh A; GEMINI 2 Study Group. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2013 Aug 22;369(8):711-21. doi: 10.1056/NEJMoa1215739.

  PMID: 23964933 BACKGROUND

• Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A; GEMINI 1 Study Group. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013 Aug 22;369(8):699-710. doi: 10.1056/NEJMoa1215734.

  PMID: 23964932 BACKGROUND

• Sandborn WJ, Colombel JF, Enns R, Feagan BG, Hanauer SB, Lawrance IC, Panaccione R, Sanders M, Schreiber S, Targan S, van Deventer S, Goldblum R, Despain D, Hogge GS, Rutgeerts P; International Efficacy of Natalizumab as Active Crohn's Therapy (ENACT-1) Trial Group; Evaluation of Natalizumab as Continuous Therapy (ENACT-2) Trial Group. Natalizumab induction and maintenance therapy for Crohn's disease. N Engl J Med. 2005 Nov 3;353(18):1912-25. doi: 10.1056/NEJMoa043335.

  PMID: 16267322 BACKGROUND

• Sands BE, Feagan BG, Rutgeerts P, Colombel JF, Sandborn WJ, Sy R, D'Haens G, Ben-Horin S, Xu J, Rosario M, Fox I, Parikh A, Milch C, Hanauer S. Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology. 2014 Sep;147(3):618-627.e3. doi: 10.1053/j.gastro.2014.05.008. Epub 2014 May 21.

  PMID: 24859203 BACKGROUND

• Arjis I, De Hertogh G, Machiels K, et al. Mucosal gene expression of cell adhesion molecules, chemokines, and chemokine receptors in patients with inflammatory bowel disease before and after infliximab treatment. American Journal of Gastroenterology. April 2011;106:748-761 Biancheri P, Di Sabatino A, Rovedatti L, et al. Effect of tumor necrosis factor-alpha blockade on mucosal addressin cell-adhesion molecule-1 in Crohn's disease. Inflammatory Bowel Disease. Feb 2013;19(2):259-264.

  BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, mucosal tissue

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases

Study Officials

• Marla C. Dubinsky, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2015
• First Posted: April 22, 2015
• Study Start: June 1, 2015
• Primary Completion: June 13, 2017
• Study Completion: June 13, 2017
• Last Updated: September 13, 2017

Record last verified: 2017-09

Locations

US (1)