Investigation of the Faecal Loss of Vedolizumab and Its Role in Influencing Serum Drug Levels, Outcomes and Response in Ulcerative Colitis

Ulcerative Colitis Clinical Trial

— FAVOUR  

Official title:

Investigation of the Faecal Loss of Vedolizumab and Its Role in Influencing Serum Drug Levels, Outcomes and Response in Ulcerative Colitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04006080
• Other study ID #: 2018-002794-21
• Status: Recruiting
• Phase: Phase 4
• Start date: July 1, 2019
• Est. completion date: March 2020

Study information

• Verified date: July 2019
• Source: Guy's and St Thomas' NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to study the loss of vedolizumab in stool in patients with active ulcerative colitis (UC).

Patients with moderate-to-severe UC who are commencing induction therapy with vedolizumab will be enrolled into a prospective study and stool will be collected for faecal vedolizumab measurement at days 1, 4 and 7; and again at weeks 2, 6 and 14. They will also be evaluated at three time-points (weeks 2, 6 and 14) for clinical and biochemical UC disease activity as well as serum vedolizumab concentrations and anti-vedolizumab antibodies.

Description:

Primary objective

• To determine whether vedolizumab is present in significant quantities in the stool of patients receiving induction therapy with vedolizumab for active UC.

Secondary objective (s)

• To evaluate whether the presence and quantity of vedolizumab in stool can be used to predict primary non-response to vedolizumab.

• To explore whether a correlation exists between stool vedolizumab concentrations, serum vedolizumab concentrations and UC disease activity and extent.

• To determine whether there is a correlation between stool and serum vedolizumab levels and trafficking of Th1/Th17 effector memory CD4+ T-cells (the key pathogenic subset in IBD) to the colon in UC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 2020
• Est. primary completion date: March 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Aged 18 years or over, either male or female

• Moderate-to-severe UC, defined as:

• SCCAI > 5 and, i. A raised fecal calprotectin (> 59 µg/g) or, ii. A raised CRP (> 5 mg/L) or, iii. Endoscopic disease activity Mayo 2 or above, Evaluated within 6 weeks of study enrollment

• Commencing vedolizumab treatment

• Sufficient English language skills to understand the patient information sheet and consent form

Exclusion Criteria:

• Contra-indication to vedolizumab (i.e. known serious or severe hypersensitivity reaction to vedolizumab or any of its excipients)

• Imminent need for colectomy (i.e. colectomy is being planned)

• Previous ileoanal pouch formation

• Active severe infections such as tuberculosis, sepsis, cytomegalovirus, listeriosis, and opportunistic infections

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Biological:
• Vedolizumab
Intravenously administered selective leukocyte adhesion molecule inhibitor

Locations

Country	Name	City	State
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
Guy's and St Thomas' NHS Foundation Trust	Takeda

Country where clinical trial is conducted

United Kingdom, 

References & Publications (8)

Bodger K, Ormerod C, Shackcloth D, Harrison M; IBD Control Collaborative. Development and validation of a rapid, generic measure of disease control from the patient's perspective: the IBD-control questionnaire. Gut. 2014 Jul;63(7):1092-102. doi: 10.1136/gutjnl-2013-305600. Epub 2013 Oct 9. — View Citation

D'Haens G, Sandborn WJ, Feagan BG, Geboes K, Hanauer SB, Irvine EJ, Lémann M, Marteau P, Rutgeerts P, Schölmerich J, Sutherland LR. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology. 2007 Feb;132(2):763-86. Epub 2006 Dec 20. Review. — View Citation

Globig AM, Hennecke N, Martin B, Seidl M, Ruf G, Hasselblatt P, Thimme R, Bengsch B. Comprehensive intestinal T helper cell profiling reveals specific accumulation of IFN-?+IL-17+coproducing CD4+ T cells in active inflammatory bowel disease. Inflamm Bowel Dis. 2014 Dec;20(12):2321-9. doi: 10.1097/MIB.0000000000000210. — View Citation

Jairath V, Khanna R, Zou GY, Stitt L, Mosli M, Vandervoort MK, D'Haens G, Sandborn WJ, Feagan BG, Levesque BG. Development of interim patient-reported outcome measures for the assessment of ulcerative colitis disease activity in clinical trials. Aliment Pharmacol Ther. 2015 Nov;42(10):1200-10. doi: 10.1111/apt.13408. Epub 2015 Sep 21. — View Citation

Marchal-Bressenot A, Salleron J, Boulagnon-Rombi C, Bastien C, Cahn V, Cadiot G, Diebold MD, Danese S, Reinisch W, Schreiber S, Travis S, Peyrin-Biroulet L. Development and validation of the Nancy histological index for UC. Gut. 2017 Jan;66(1):43-49. doi: 10.1136/gutjnl-2015-310187. Epub 2015 Oct 13. — View Citation

Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987 Dec 24;317(26):1625-9. — View Citation

Travis SP, Schnell D, Krzeski P, Abreu MT, Altman DG, Colombel JF, Feagan BG, Hanauer SB, Lémann M, Lichtenstein GR, Marteau PR, Reinisch W, Sands BE, Yacyshyn BR, Bernhardt CA, Mary JY, Sandborn WJ. Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Gut. 2012 Apr;61(4):535-42. doi: 10.1136/gutjnl-2011-300486. Epub 2011 Oct 13. — View Citation

Travis SP, Schnell D, Krzeski P, Abreu MT, Altman DG, Colombel JF, Feagan BG, Hanauer SB, Lichtenstein GR, Marteau PR, Reinisch W, Sands BE, Yacyshyn BR, Schnell P, Bernhardt CA, Mary JY, Sandborn WJ. Reliability and initial validation of the ulcerative colitis endoscopic index of severity. Gastroenterology. 2013 Nov;145(5):987-95. doi: 10.1053/j.gastro.2013.07.024. Epub 2013 Jul 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in vedolizumab concentrations in stool	Evaluated using an enzyme-linked immunosorbent assay (ELISA)	Days 1, 4 and 7; and weeks 2, 6 and 14
Secondary	UC endoscopic activity	Evaluated using the Mayo Endoscopic Score: Mayo 0 = normal; Mayo 1= mild inflammation; Mayo 2 = moderate inflammation; Mayo 3 = severe inflammation	Baseline and week 14
Secondary	UC endoscopic activity	Evaluated using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score: Vascular pattern= Normal (0), patchy loss (1), obliterated (2); Bleeding = None (0), mucosal (1), luminal mild (2), luminal moderate (3); Erosions/ulcers = None (0), erosions (1), superfical ulcer (2), deep ulcer (3)	Baseline and week 14
Secondary	Clinical UC disease activity	Evaluated using Patient Reported Outcome 2 (PRO2) Questionnaire: Stool frequency= normal (0), 1-2 more (1), 3-4 more (2), 5 or more stools than normal (3); Rectal bleeding= no blood (0), streaks of blood <50% time (1), obvious blood >50% time (2), blood alone passes (3)	Day 0, weeks 2, 6 and 14
Secondary	Vedolizumab serum concentrations	Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)	Weeks 2, 6 and 14
Secondary	Vedolizumab anti-drug antibody levels	Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)	Weeks 2, 6 and 14
Secondary	Faecal calprotectin	Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)	Day 0, weeks 2, 6 and 14
Secondary	Serum CRP (mg/L)		Day 0, weeks 2, 6 and 14
Secondary	Serum albumin (g/L) [40-52g/L]		Day 0, weeks 2, 6 and 14
Secondary	Quality of life questionnaire	IBD-Control questionnaire	Day 0, weeks 2, 6 and 14
Secondary	Clinical UC disease activity	Evaluated using the Simple Clinical Colitis Activity Index score: Bowel frequency day= 0-3 (0), 4-6 (1), 7-9 (2), >9 (3); Bowel frequency night= 0 (0), 1-3 (1), 4-6 (2); Urgency of defectation= None(0), Hurry (1), immediately (2), incontinence (3); Blood in stool = None (0), trace (1), occasional frank (2), usually frank (3); General well being= very well (0), slightly below par (1), poor (2), very poor (3), terrible (4); Extracolonic features (1 point for each) = arthritis, uveitis, erythema nodosum, pyoderma gangrenosum. Remission SCCAI = 2; Response SCCAI = 5, with a decrease by = 2; Relapse SCCAI = 5 (following a response)	Day 0, weeks 2, 6 and 14
Secondary	UC histological activity	Evaluated using Nancy Histological Index	Day 0 and week 14