The Impact of Anti-TNF Exposure on Vedolizumab Effectiveness

Ulcerative Colitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02423512
• Other study ID #: GCO 15-0651
• Secondary ID: IISR-2015-100947
• Status: Completed
• Phase: N/A
• First received: April 17, 2015
• Last updated: September 11, 2017
• Start date: June 2015
• Est. completion date: June 13, 2017

Study information

• Verified date: September 2017
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 13, 2017
• Est. primary completion date: June 13, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Crohn Disease
• Crohn's Disease
• Inflammatory Bowel Disease
• Inflammatory Bowel Diseases
• Intestinal Diseases
• Ulcer
• Ulcerative Colitis

Locations

Country	Name	City	State
United States	Susan and Leonard Feinstein Inflammatory Bowel Disease Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai

Country where clinical trial is conducted

United States, 

References & Publications (5)

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.

Baumgart D, Sandbown W. Crohn's disease. Lancet. Nov 2012;380(9853):1590-605 Sandborn W, Feagan B, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn's disease. New England Journal of Medicine. Aug 2013;369(8):711-721.

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. — View Citation

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. Erratum in: N Engl J Med. 2015 May 21;372(21):2074. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	biomarker MAdCAM-1	change in biomarker MAdCAM-1 at week 14 as compared to baseline	baseline and week 14
Secondary	biomarker alpha 4 beta 7	change in biomarker alpha 4 beta 7 at week 14 as compared to baseline	baseline and week 14
Secondary	TNF levels	change in TNF levels at week 14 as compared to baseline	baseline and week 14
Secondary	mucosal drug concentration	mucosal drug concentration in those undergoing colonoscopy	week 14
Secondary	mucosal drug concentration	mucosal drug concentration in those undergoing colonoscopy	week 30
Secondary	vedolizumab drug concentration	vedolizumab drug concentration in those patients scheduled for vedolizumab therapy	week 14
Secondary	vedolizumab drug concentration	vedolizumab drug concentration in those patients scheduled for vedolizumab therapy	week 30