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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Biological: Vedolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vedolizumab<br> | Biological: Vedolizumab<br>* Intravenously administered selective leukocyte adhesion molecule inhibitor<br>* Other names: Entyvio;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| Vedolizumab serum concentrations | Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA) | Weeks 2, 6 and 14 | 
| Vedolizumab anti-drug antibody levels | Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA) | Weeks 2, 6 and 14 | 
| Faecal calprotectin | Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA) | Day 0, weeks 2, 6 and 14 | 
| Serum CRP (mg/L) |  | Day 0, weeks 2, 6 and 14 | 
| Serum albumin (g/L) [40-52g/L] |  | Day 0, weeks 2, 6 and 14 | 
| Quality of life questionnaire | IBD-Control questionnaire | Day 0, weeks 2, 6 and 14 | 
| 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 | 
| UC histological activity | Evaluated using Nancy Histological Index | Day 0 and week 14 |