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

Guy's and St Thomas' NHS Foundation Trust30 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Ulcerative Colitis

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Change in vedolizumab concentrations in stool

Evaluated using an enzyme-linked immunosorbent assay (ELISA)

Time frame: Days 1, 4 and 7; and weeks 2, 6 and 14

Secondary Outcomes

UC endoscopic activity

Evaluated using the Mayo Endoscopic Score: Mayo 0 = normal; Mayo 1= mild inflammation; Mayo 2 = moderate inflammation; Mayo 3 = severe inflammation

Time frame: 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)

Time frame: 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)

Time frame: Day 0, weeks 2, 6 and 14

Vedolizumab serum concentrations

Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)

Time frame: Weeks 2, 6 and 14

Vedolizumab anti-drug antibody levels

Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)

Time frame: Weeks 2, 6 and 14

Faecal calprotectin

Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)

Time frame: Day 0, weeks 2, 6 and 14

Serum CRP (mg/L)

Time frame: Day 0, weeks 2, 6 and 14

Serum albumin (g/L) [40-52g/L]

Time frame: Day 0, weeks 2, 6 and 14

Quality of life questionnaire

IBD-Control questionnaire

Time frame: 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)

Time frame: Day 0, weeks 2, 6 and 14

UC histological activity

Evaluated using Nancy Histological Index

Time frame: Day 0 and week 14

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes