Study of the Golimumab Exposure-Response Relationship Using Serum Trough Levels

Phase 4

Completed

Conditions: Ulcerative Colitis

Interventions: Drug: Golimumab

Registration Number: NCT03124121

Lead Sponsor: Guy's and St Thomas' NHS Foundation Trust

Brief Summary: The purpose of this study is to gain insight into the exposure-response relationship of golimumab in moderate-to-severe Ulcerative Colitis (UC).

Patients commencing induction therapy with golimumab will be enrolled into a prospective study and evaluated at three time-points (weeks 6, 10 and 14) for clinical and biochemical UC disease activity as well as serum golimumab concentrations and the presence of anti-golimumab antibodies. Patients already established on stable golimumab maintenance therapy will be enrolled into a cross-sectional study with the same evaluations taken at a single time point.

Detailed Description: The study will involve two study groups designed to offer insights into the pharmacokinetics of golimumab during induction and maintenance therapy:

Cohort 1: Patients commencing golimumab induction therapy will be included in a prospective, observational study.

Cohort 2: Patients receiving golimumab maintenance therapy will be included in a cross-sectional, observational study.

Primary objective: To define a week 6 serum golimumab concentration that predicts response at week 14.

Secondary objective: To define serum golimumab concentrations at weeks 6, 10 and 14 that predict response at each time point, respectively and at week 14.

Exploratory objectives:

Correlations between serum golimumab concentrations and novel disease activity indices (PRO2), biochemical markers of disease activity (CRP, faecal calprotectin) and quality of life indices (IBD-Q and IBD-Control).

Correlations between the presence of anti-golimumab antibodies, serum golimumab concentrations and UC disease activity.

This study will also generate data that can be used to validate a commercially available golimumab assay as well as a novel patient reported outcome (PRO) assessment of clinical UC disease activity.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 112

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Induction cohort	Golimumab	Golimumab induction therapy
Maintenance cohort	Golimumab	Golimumab maintenance therapy

Primary Outcome Measures

Name	Time	Method
Serum Golimumab Concentration (μg/ml)	Week 6 during induction therapy and at the point of study entry during maintenance	Evaluated using an enzyme-linked immunosorbent assay (ELISA)

Secondary Outcome Measures

Name	Time	Method
Serum Albumin (g/L)	Week 14 during induction therapy and at the point of study entry during maintenance	Serum protein marker with higher values associated with increasing inflammatory activity and lower serum levels of anti-TNF agents (such as golimumab)
Number of Patients in Clinical Remission	Week 14 during induction therapy and at the point of study entry during maintenance therapy	Evaluated using the Simple Clinical Colitis Activity Index (SCCAI). Remission defined as SCCAI \< 3.
Faecal Calprotectin (μg/g)	Week 14 during induction therapy and at the point of study entry during maintenance	Faecal inflammatory marker with higher values suggestive of increasing biochemical disease activity
Serum C-Reactive Protein (mg/L)	Week 14 during induction therapy and at the point of study entry during maintenance	Serum inflammatory marker with higher values suggestive of increasing biochemical disease activity
Clinical UC Disease Activity	Week 14 during maintenance therapy and at the point of study entry during maintenance	Evaluated using Patient Reported Outcome 2 (PRO2). PRO2 ranges from 0-5 with higher scores denoting increasing clinical disease activity.
Quality of Life (IBD-Control)	Week 14 during induction therapy and at the point of study entry during maintenance therapy	Evaluated using IBD-Control questionnaires. IBD-Control scores range from 0-16 with higher scores denoting better quality of life.
Number of Patients With Detectable Anti-golimumab Antibodies	At any study time point during induction therapy (weeks 6, 10 or 14) and at the point if study entry during maintenance	Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)