Clinical trial NCT04006080: Investigation of the Faecal Loss of Vedolizumab and Its Role in Influencing Serum Drug Levels, Outcomes and Response in Ulcerative Colitis
Official title: Investigation of the Faecal Loss of Vedolizumab and Its Role in Influencing Serum Drug Levels, Outcomes and Response in Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Ulcerative Colitis
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Takeda
First posted: 2019-07-02
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in vedolizumab concentrations in stool
timeFrame: Days 1, 4 and 7; and weeks 2, 6 and 14
Secondary outcomes:
measure: UC endoscopic activity
timeFrame: Baseline and week 14
measure: UC endoscopic activity
timeFrame: Baseline and week 14
measure: Clinical UC disease activity
timeFrame: Day 0, weeks 2, 6 and 14
measure: Vedolizumab serum concentrations
timeFrame: Weeks 2, 6 and 14
measure: Vedolizumab anti-drug antibody levels
timeFrame: Weeks 2, 6 and 14
measure: Faecal calprotectin
timeFrame: Day 0, weeks 2, 6 and 14
measure: Serum CRP (mg/L)
timeFrame: Day 0, weeks 2, 6 and 14
measure: Serum albumin (g/L) [40-52g/L]
timeFrame: Day 0, weeks 2, 6 and 14
measure: Quality of life questionnaire
timeFrame: Day 0, weeks 2, 6 and 14
measure: Clinical UC disease activity
timeFrame: Day 0, weeks 2, 6 and 14
measure: UC histological activity
timeFrame: Day 0 and week 14
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
Study officials:
References:
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