Ulcerative Colitis
Conditions
Brief 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.
Detailed 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.
Interventions
BIOLOGICALVedolizumab
Intravenously administered selective leukocyte adhesion molecule inhibitor
Sponsors
Takeda
Guy's and St Thomas' NHS Foundation Trust
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in vedolizumab concentrations in stool | Days 1, 4 and 7; and weeks 2, 6 and 14 | Evaluated using an enzyme-linked immunosorbent assay (ELISA) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical UC disease activity | Day 0, weeks 2, 6 and 14 | 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) |
| Vedolizumab serum concentrations | Weeks 2, 6 and 14 | Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA) |
| Vedolizumab anti-drug antibody levels | Weeks 2, 6 and 14 | Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA) |
| Faecal calprotectin | Day 0, weeks 2, 6 and 14 | Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA) |
| UC endoscopic activity | Baseline and week 14 | Evaluated using the Mayo Endoscopic Score: Mayo 0 = normal; Mayo 1= mild inflammation; Mayo 2 = moderate inflammation; Mayo 3 = severe inflammation |
| Serum albumin (g/L) [40-52g/L] | Day 0, weeks 2, 6 and 14 | — |
| Quality of life questionnaire | Day 0, weeks 2, 6 and 14 | IBD-Control questionnaire |
| UC histological activity | Day 0 and week 14 | Evaluated using Nancy Histological Index |
| Serum CRP (mg/L) | Day 0, weeks 2, 6 and 14 | — |
Countries
United Kingdom
Outcome results
None listed