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

Conditions

Ulcerative Colitis

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.

Mark Samaan, Georgina Cunningham, Gokul Tamilarasan, Shuvra Ray, Joel Mawdsley et al. (8 authors)

2021-01-011 citations

10.1136/gutjnl-2020-bsgcampus.218

P144 Therapeutic thresholds for golimumab serum concentrations during induction and maintenance: results from the GO-LEVEL study

Mark Samaan, Georgina Cunningham, Gokul Tamilarasan, Krystal Rawstron, Karim Hawash et al. (12 authors)

2021-01-01

10.1136/gutjnl-2020-bsgcampus.219

Therapeutic thresholds for golimumab serum concentrations during induction and maintenance therapy in ulcerative colitis: results from the GO‐LEVEL study

Mark Samaan, Georgina Cunningham, Aravind Gokul Tamilarasan, Luisa Beltran, Polychronis Pavlidis et al. (11 authors)

Alimentary Pharmacology & Therapeutics2020-06-0722 citations

10.1111/apt.15808

P193 Validation of the two-item UC patient-reported outcome (PRO2) against the simple clinical colitis activity index (SCCAI), measures of biochemical disease activity and quality of life

Mark Samaan, Georgina Cunningham, Gokul Tamilarasan, S Ray, Joel Mawdsley et al. (9 authors)

Journal of Crohn s and Colitis2020-01-011 citations

10.1093/ecco-jcc/jjz203.322

P723 Therapeutic thresholds for golimumab serum concentrations during induction and maintenance: Results from the GO-LEVEL study

M Samaan, Georgina Cunningham, Gokul Tamilarasan, Krystal Rawstron, Karim Hawash et al. (12 authors)

Journal of Crohn s and Colitis2020-01-01

10.1093/ecco-jcc/jjz203.851

OWE-03 Higher serum golimumab concentrations are associated with combined clinical-biochemical remission: results from the GO-LEVEL study

Mark Samaan, Georgina Cunningham, Aravind Gokul Tamilarasan, Krystal Rawstron, Karim Hawash et al. (13 authors)

2019-06-01

10.1136/gutjnl-2019-bsgabstracts.124

P683 Higher serum golimumab concentrations are significantly associated with combined clinical-biochemical remission during maintenance therapy: results from the GO-LEVEL study

M Samaan, Georgina Cunningham, Aravind Gokul Tamilarasan, Krystal Rawstron, Karim Hawash et al. (13 authors)

Journal of Crohn s and Colitis2019-01-25

10.1093/ecco-jcc/jjy222.807

Interventions

DRUGGolimumab

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

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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)

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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
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)
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.
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)

Countries

United Kingdom

Participant flow

Participants by arm

Arm	Count
Golimumab Induction Therapy Patients commencing golimumab	39
Golimumab Maintenance Therapy Patients receiving golimumab maintenance therapy	67
Total	106

Baseline characteristics

Characteristic	Golimumab Induction Therapy	Golimumab Maintenance Therapy	Total
Age, Continuous	37 years	36 years	36 years
Race and Ethnicity Not Collected	—	—	0 Participants
Sex: Female, Male Female	17 Participants	30 Participants	47 Participants
Sex: Female, Male Male	22 Participants	37 Participants	59 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 42	0 / 70
other Total, other adverse events	0 / 0	0 / 0
serious Total, serious adverse events	4 / 42	0 / 70

Outcome results

Primary

Serum Golimumab Concentration (μg/ml)

Evaluated using an enzyme-linked immunosorbent assay (ELISA)

Time frame: Week 6 during induction therapy and at the point of study entry during maintenance

Arm	Measure	Value (MEDIAN)
Golimumab Induction Therapy	Serum Golimumab Concentration (μg/ml)	3.3 ug/ml
Golimumab Maintenance Therapy	Serum Golimumab Concentration (μg/ml)	2.4 ug/ml

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.

Time frame: Week 14 during maintenance therapy and at the point of study entry during maintenance

Arm	Measure	Value (MEDIAN)
Golimumab Induction Therapy	Clinical UC Disease Activity	1 score on a scale
Golimumab Maintenance Therapy	Clinical UC Disease Activity	0 score on a scale

Secondary

Faecal Calprotectin (μg/g)

Faecal inflammatory marker with higher values suggestive of increasing biochemical disease activity

Time frame: Week 14 during induction therapy and at the point of study entry during maintenance

Arm	Measure	Value (MEDIAN)
Golimumab Induction Therapy	Faecal Calprotectin (μg/g)	46 ug/g
Golimumab Maintenance Therapy	Faecal Calprotectin (μg/g)	57 ug/g

Secondary

Number of Patients in Clinical Remission

Evaluated using the Simple Clinical Colitis Activity Index (SCCAI). Remission defined as SCCAI \< 3.

Time frame: Week 14 during induction therapy and at the point of study entry during maintenance therapy

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Golimumab Induction Therapy	Number of Patients in Clinical Remission	22 Participants
Golimumab Maintenance Therapy	Number of Patients in Clinical Remission	41 Participants

Secondary

Number of Patients With Detectable Anti-golimumab Antibodies

Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)

Time frame: At any study time point during induction therapy (weeks 6, 10 or 14) and at the point if study entry during maintenance

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Golimumab Induction Therapy	Number of Patients With Detectable Anti-golimumab Antibodies	1 Participants
Golimumab Maintenance Therapy	Number of Patients With Detectable Anti-golimumab Antibodies	0 Participants

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.

Time frame: Week 14 during induction therapy and at the point of study entry during maintenance therapy

Arm	Measure	Value (MEDIAN)
Golimumab Induction Therapy	Quality of Life (IBD-Control)	12.5 score on a scale
Golimumab Maintenance Therapy	Quality of Life (IBD-Control)	14 score on a scale

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)

Time frame: Week 14 during induction therapy and at the point of study entry during maintenance

Arm	Measure	Value (MEDIAN)
Golimumab Induction Therapy	Serum Albumin (g/L)	46 g/L
Golimumab Maintenance Therapy	Serum Albumin (g/L)	47 g/L

Secondary

Serum C-Reactive Protein (mg/L)

Serum inflammatory marker with higher values suggestive of increasing biochemical disease activity

Time frame: Week 14 during induction therapy and at the point of study entry during maintenance

Arm	Measure	Value (MEDIAN)
Golimumab Induction Therapy	Serum C-Reactive Protein (mg/L)	1 mg/L
Golimumab Maintenance Therapy	Serum C-Reactive Protein (mg/L)	1 mg/L

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

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Baseline characteristics

Adverse events

Outcome results

Serum Golimumab Concentration (μg/ml)

Clinical UC Disease Activity

Faecal Calprotectin (μg/g)

Number of Patients in Clinical Remission

Number of Patients With Detectable Anti-golimumab Antibodies

Quality of Life (IBD-Control)

Serum Albumin (g/L)

Serum C-Reactive Protein (mg/L)