Clinical trial NCT03124121: Study of the Golimumab Exposure-Response Relationship Using Serum Trough Levels
Official title: Study of the Golimumab Exposure-Response Relationship Using Serum Trough Levels
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ulcerative Colitis
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-04-21
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Serum Golimumab Concentration (μg/ml)
timeFrame: Week 6 during induction therapy and at the point of study entry during maintenance
Secondary outcomes:
measure: Number of Patients in Clinical Remission
timeFrame: Week 14 during induction therapy and at the point of study entry during maintenance therapy
measure: Faecal Calprotectin (μg/g)
timeFrame: Week 14 during induction therapy and at the point of study entry during maintenance
measure: Serum C-Reactive Protein (mg/L)
timeFrame: Week 14 during induction therapy and at the point of study entry during maintenance
measure: Serum Albumin (g/L)
timeFrame: Week 14 during induction therapy and at the point of study entry during maintenance
measure: Clinical UC Disease Activity
timeFrame: Week 14 during maintenance therapy and at the point of study entry during maintenance
measure: Quality of Life (IBD-Control)
timeFrame: Week 14 during induction therapy and at the point of study entry during maintenance therapy
measure: Number of Patients With Detectable Anti-golimumab Antibodies
timeFrame: At any study time point during induction therapy (weeks 6, 10 or 14) and at the point if study entry during maintenance
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guy's & St Thomas' NHS Foundation Trust
Study officials:
References:
citation: Samaan MA, Cunningham G, Tamilarasan AG, Beltran L, Pavlidis P, Ray S, Mawdsley J, Anderson SH, Sanderson JD, Arkir Z, Irving PM. Therapeutic thresholds for golimumab serum concentrations during induction and maintenance therapy in ulcerative colitis: results from the GO-LEVEL study. Aliment Pharmacol Ther. 2020 Jul;52(2):292-302. doi: 10.1111/apt.15808. Epub 2020 Jun 7.