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

Ulcerative Colitis Clinical Trial

— GO-LEVEL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03124121
• Other study ID #: 2017-001374-42
• Status: Completed
• Phase: Phase 4
• Start date: September 5, 2017
• Est. completion date: September 30, 2019

Study information

• Verified date: June 2021
• Source: Guy's and St Thomas' NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: September 30, 2019
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Colitis, Ulcerative
• Ulcerative Colitis

Intervention

Drug:
• Golimumab
A biologic agent which acts by antagonising the effects of tumour necrosis factor (TNF) alpha

Locations

Country	Name	City	State
United Kingdom	Guy's & St Thomas' NHS Foundation Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
Guy's and St Thomas' NHS Foundation Trust	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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