Ulcerative Colitis - Vedolizumab- With/Without Prior Exposure to Anti-TNF（Tumor Necrosis Factor）Therapy

Ulcerative Colitis Clinical Trial

Official title:

A Case-control Study to Evaluate the Immunoinflammatory Effect of Prior Exposure to Anti-TNF Therapy in Patients With Ulcerative Colitis Starting Vedolizumab Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03802214
• Other study ID #: IRB48889
• Status: Terminated
• Start date: October 29, 2020
• Est. completion date: December 11, 2020

Study information

• Verified date: December 2020
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

A case-control study to evaluate the immunoinflammatory effect of prior exposure to anti-TNF therapy in patients with ulcerative colitis starting vedolizumab therapy

Description:

Inflammatory bowel disease (IBD)- ulcerative colitis (UC) and Crohn's disease (CD)- are chronic conditions of the gastrointestinal tract. Treatment generally consists of immunosuppression to modify the dysregulated immune responses. Vedolizumab, an inhibitor of α4β7, is a highly effective therapy for treating IBD, that minimized adverse effects through its gut selective inhibition of lymphocyte trafficking. However, the mechanism of action remains incompletely characterized especially in those previously treated to other biologics and why some patients are either vedolizumab non-responders or fail to respond over time. We would like to address the question whether anti-TNF non-responders as well as those that either do not respond or fail overtime to respond to vedolizumab identifies a specific population with difficult to treat disease that have alternate trafficking patterns and whether prior exposure to anti-TNF alters the mucosal immune responses, and/or trafficking patterns when compared to anti-TNF naive patients that may help explain impaired response to vedolizumab induction therapy.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: December 11, 2020
• Est. primary completion date: December 11, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• adult patients (>18 years old)

• clinical diagnosis of inflammatory bowel disease (Ulcerative Colitis)

• clinical indication for biologic therapy

• naive or failed anti-TNF therapy previously

Exclusion Criteria:

• patients allergic or intolerant to vedolizumab,

• past use of vedolizumab;

• patient unable to give consent to enter the study

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Vedolizumab
standard vedolizumab induction (300mg IV at week 0, 2, 6)

Locations

Country	Name	City	State
Canada	University of Western Ontario	London	Ontario
United States	Stanford University	Stanford	California

Sponsors (4)

Lead Sponsor	Collaborator
Stanford University	Takeda, University of California, San Diego, University of Western Ontario, Canada

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (7)

Boden EK, Shows DM, Chiorean MV, Lord JD. Identification of Candidate Biomarkers Associated with Response to Vedolizumab in Inflammatory Bowel Disease. Dig Dis Sci. 2018 Sep;63(9):2419-2429. doi: 10.1007/s10620-018-4924-8. Epub 2018 Jan 25. — View Citation

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

Kobayashi M, Hoshino H, Masumoto J, Fukushima M, Suzawa K, Kageyama S, Suzuki M, Ohtani H, Fukuda M, Nakayama J. GlcNAc6ST-1-mediated decoration of MAdCAM-1 protein with L-selectin ligand carbohydrates directs disease activity of ulcerative colitis. Inflamm Bowel Dis. 2009 May;15(5):697-706. doi: 10.1002/ibd.20827. — View Citation

Rosario M, Dirks NL, Gastonguay MR, Fasanmade AA, Wyant T, Parikh A, Sandborn WJ, Feagan BG, Reinisch W, Fox I. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease. Aliment Pharmacol Ther. 2015 Jul;42(2):188-202. doi: 10.1111/apt.13243. Epub 2015 May 20. Erratum in: Aliment Pharmacol Ther. 2015 Nov;42(9):1135. — View Citation

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. — View Citation

Schmitt H, Billmeier U, Dieterich W, Rath T, Sonnewald S, Reid S, Hirschmann S, Hildner K, Waldner MJ, Mudter J, Hartmann A, Grützmann R, Neufert C, Münster T, Neurath MF, Atreya R. Expansion of IL-23 receptor bearing TNFR2+ T cells is associated with molecular resistance to anti-TNF therapy in Crohn's disease. Gut. 2019 May;68(5):814-828. doi: 10.1136/gutjnl-2017-315671. Epub 2018 May 30. — View Citation

Suzawa K, Kobayashi M, Sakai Y, Hoshino H, Watanabe M, Harada O, Ohtani H, Fukuda M, Nakayama J. Preferential induction of peripheral lymph node addressin on high endothelial venule-like vessels in the active phase of ulcerative colitis. Am J Gastroenterol. 2007 Jul;102(7):1499-509. Epub 2007 Apr 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Analysis of blood and tissue leukocytes (T cells, B cells and Dendritic cells)	Analysis of blood and tissue leukocytes (T cells, B cells and Dendritic cells) in patients with and without prior anti-TNF exposure	changes from enrollment to end of treatment (week 14)
Secondary	Analysis of the serum and tissue concentrations of inflammatory markers (interleukins)	Analysis of the serum and tissue concentrations of inflammatory markers (interleukins) in vedolizumab responders versus non-responders	changes from enrollment to end of treatment (week 14)
Secondary	Analysis of the serum and tissue concentrations of vedolizumab	Analysis of the serum and tissue concentrations of vedolizumab in patients with and without prior anti-TNF exposure	changes from enrollment to end of treatment (week 14)