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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Golimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for cohort 1: Aged 18 years or over 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 4 weeks of study enrollment Commencing golimumab treatment Written informed consent to participate Sufficient English language skills to understand the patient information sheet and consent form Inclusion Criteria for cohort 2: Aged 18 years or over Receiving golimumab treatment for UC for over 18 weeks (6 injections) Written informed consent to participate Sufficient English language skills to understand the patient information sheet and consent form Exclusion Criteria (cohort 1 only): Contra-indication to golimumab: tuberculosis or severe infections Imminent need for colectomy (i.e. colectomy is being planned) Previous primary non-response to anti-TNF therapy in the opinion of the investigator Previous treatment with more than one anti-TNF therapy (excluding golimumab)

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Induction cohort<br>Golimumab induction therapy | Drug: Golimumab<br>* A biologic agent which acts by antagonising the effects of tumour necrosis factor (TNF) alpha<br>* Other names: Simponi;|
| Other: Maintenance cohort<br>Golimumab maintenance therapy | Drug: Golimumab<br>* A biologic agent which acts by antagonising the effects of tumour necrosis factor (TNF) alpha<br>* Other names: Simponi;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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