The Impact of Anti-TNF Exposure on Vedolizumab Effectiveness

The Impact of Anti-TNF Exposure on Vedolizumab Effectiveness: A Biomarker Study.

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.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease; Ulcerative Colitis; Inflammatory Bowel Disease

Detailed Description

Patients will be enrolled in the study when they are selected to initiate vedolizumab therapy. Vedolizumab is an intravenous infusion given at increasing intervals. The first infusion of vedolizumab will be considered baseline. Patients may be enrolled at baseline or at colonoscopy prior to the first scheduled infusion of vedolizumab (pre-treatment visit). The standard induction protocol for vedolizumab consists of infusions at week 0 (baseline), week 2, and week 6. Vedolizumab, as per standard-of-care, is then continued at an interval of every 8 weeks following induction therapy. Vedolizumab treatment will be prescribed as per standard practice and will be prescribed regardless of participation in this study. Patients will not receive medication for the sole purpose of this research. Treatment decisions including timing of wash out period between anti-TNf and vedolizumab will be made by the subject's physician and not per the research protocol. There will not be a protocolized washout period for patients previously receiving anti-TNF therapy because treatment will be standard of care and per the directing physician.

Standard of care laboratory tests will be performed by the clinical laboratory at Mount Sinai Hospital. All other measurements will be completed at Prometheus Therapeutics & Diagnostics in San Diego, California or at a Takeda identified lab for vedolizumab concentrations and antibodies.

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Susan and Leonard Feinstein Inflammatory Bowel Disease Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

-Patients with prior exposure to vedolizumab or natalizumab

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
biomarker MAdCAM-1	change in biomarker MAdCAM-1 at week 14 as compared to baseline	baseline and week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
biomarker alpha 4 beta 7	change in biomarker alpha 4 beta 7 at week 14 as compared to baseline	baseline and week 14
TNF levels	change in TNF levels at week 14 as compared to baseline	baseline and week 14
mucosal drug concentration	mucosal drug concentration in those undergoing colonoscopy	week 14
mucosal drug concentration	mucosal drug concentration in those undergoing colonoscopy	week 30
vedolizumab drug concentration	vedolizumab drug concentration in those patients scheduled for vedolizumab therapy	week 14
vedolizumab drug concentration	vedolizumab drug concentration in those patients scheduled for vedolizumab therapy	week 30

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Marla C. Dubinsky, MD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

General Publications

• 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.
• 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.
• 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. Erratum In: N Engl J Med. 2015 May 21;372(21):2074.
• 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.
• Biancheri P, Di Sabatino A, Rovedatti L, Giuffrida P, Calarota SA, Vetrano S, Vidali F, Pasini A, Danese S, Corazza GR, MacDonald TT. Effect of tumor necrosis factor-alpha blockade on mucosal addressin cell-adhesion molecule-1 in Crohn's disease. Inflamm Bowel Dis. 2013 Feb;19(2):259-64. doi: 10.1097/MIB.0b013e31828100a4.

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): June 13, 2017
• Study Completion (Actual): June 13, 2017

Study Registration Dates

• First Submitted: April 17, 2015
• First Submitted That Met QC Criteria: April 17, 2015
• First Posted (Estimate): April 22, 2015

Study Record Updates

• Last Update Posted (Actual): September 13, 2017
• Last Update Submitted That Met QC Criteria: September 11, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; Crohn's Disease; Inflammatory Bowel Diseases; Vedolizumab; MADCAM1; integrin alpha4beta7
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Ulcer; Inflammatory Bowel Diseases; Crohn Disease; Intestinal Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: GCO 15-0651; IISR-2015-100947 (Other Identifier: Takeda Pharmaceuticals)