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

• Sponsor: Guy's and St Thomas' NHS Foundation Trust (Other)
• Overall Status: Completed
• CT.gov ID: NCT03124121
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 112
• Location: 1
• Arms: 2
• Actual Duration (Months): 24.8
• Patients Per Site Per Month: 4.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Drug: Golimumab	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 112 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Study of the Golimumab Exposure-Response Relationship Using Serum Trough Levels
• Actual Study Start Date: Sep 5, 2017
• Actual Primary Completion Date: Sep 30, 2019
• Actual Study Completion Date: Sep 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: Induction cohort Golimumab induction therapy	Drug: Golimumab; A biologic agent which acts by antagonising the effects of tumour necrosis factor (TNF) alpha; Other Names: Simponi
Other: Maintenance cohort Golimumab maintenance therapy	Drug: Golimumab; A biologic agent which acts by antagonising the effects of tumour necrosis factor (TNF) alpha; Other Names: Simponi

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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

3. 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

4. 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)

5. 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.

6. 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.

7. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Guy's & St Thomas' NHS Foundation Trust	London		United Kingdom

Sponsors and Collaborators

• Guy's and St Thomas' NHS Foundation Trust
• Merck Sharp & Dohme LLC

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 13, 2019
• Informed Consent Form - Oct 1, 2017

More Information

Publications

None provided.

• Responsible Party: Guy's and St Thomas' NHS Foundation Trust
• ClinicalTrials.gov Identifier: NCT03124121
• Other Study ID Numbers: 2017-001374-42
• First Posted: Apr 21, 2017
• Last Update Posted: Jul 6, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Colitis; Colitis, Ulcerative; Golimumab

Study Results

Participant Flow

Arm/Group Title	Golimumab Induction Therapy	Golimumab Maintenance Therapy
Arm/Group Description	Patients commencing golimumab	Patients receiving golimumab maintenance therapy
Period Title: Overall Study
STARTED	42	70
COMPLETED	39	67
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	Golimumab Induction Therapy	Golimumab Maintenance Therapy	Total
Arm/Group Description	Patients commencing golimumab	Patients receiving golimumab maintenance therapy	Total of all reporting groups
Overall Participants	39	67	106
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	37	36	36
Sex: Female, Male (Count of Participants)
Female	17 43.6%	30 44.8%	47 44.3%
Male	22 56.4%	37 55.2%	59 55.7%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Golimumab Induction Therapy	Golimumab Maintenance Therapy
Arm/Group Description	Patients commencing golimumab	Patients receiving golimumab maintenance therapy
Measure Participants	39	67
Median (Full Range) [ug/ml]	3.3	2.4

2. Secondary Outcome

Title	Number of Patients in Clinical Remission
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Induction Cohort	Maintenance Cohort
Arm/Group Description	Patients commencing golimumab	Patients receiving golimumab maintenance therapy
Measure Participants	42	67
Count of Participants [Participants]	22 56.4%	41 61.2%

3. Secondary Outcome

Title	Faecal Calprotectin (μg/g)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Golimumab Induction Therapy	Golimumab Maintenance Therapy
Arm/Group Description	Patients commencing golimumab	Patients receiving golimumab maintenance therapy
Measure Participants	42	63
Median (Full Range) [ug/g]	46	57

4. Secondary Outcome

Title	Serum C-Reactive Protein (mg/L)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Golimumab Induction Therapy	Golimumab Maintenance Therapy
Arm/Group Description	Patients commencing golimumab	Patients receiving golimumab maintenance therapy
Measure Participants	42	67
Median (Full Range) [mg/L]	1	1

5. Secondary Outcome

Title	Serum Albumin (g/L)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Golimumab Induction Therapy	Golimumab Maintenance Therapy
Arm/Group Description	Patients commencing golimumab	Patients receiving golimumab maintenance therapy
Measure Participants	42	67
Median (Full Range) [g/L]	46	47

6. Secondary Outcome

Title	Clinical UC Disease Activity
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Golimumab Induction Therapy	Golimumab Maintenance Therapy
Arm/Group Description	Patients commencing golimumab	Patients receiving golimumab maintenance therapy
Measure Participants	42	67
Median (Full Range) [score on a scale]	1	0

7. Secondary Outcome

Title	Quality of Life (IBD-Control)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Golimumab Induction Therapy	Golimumab Maintenance Therapy
Arm/Group Description	Patients commencing golimumab	Patients receiving golimumab maintenance therapy
Measure Participants	42	67
Median (Full Range) [score on a scale]	12.5	14

8. Secondary Outcome

Title	Number of Patients With Detectable Anti-golimumab Antibodies
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Golimumab Induction Therapy	Golimumab Maintenance Therapy
Arm/Group Description	Patients commencing golimumab	Patients receiving golimumab maintenance therapy
Measure Participants	42	67
Count of Participants [Participants]	1 2.6%	0 0%

Adverse Events

Time Frame	During the 14 week induction study for patients commencing treatment and at a single time point (the point of recruitment) for patients on maintenance therapy.
Adverse Event Reporting Description	Only serious adverse events (including all-cause mortality) were recorded. Non-serious adverse events were not recorded.
Arm/Group Title	Golimumab Induction Therapy		Golimumab Maintenance Therapy
Arm/Group Description	Patients commencing golimumab induction		Patients receiving golimumab maintenance therapy
All Cause Mortality
	Golimumab Induction Therapy		Golimumab Maintenance Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/70 (0%)
Serious Adverse Events
	Golimumab Induction Therapy		Golimumab Maintenance Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/42 (9.5%)		0/70 (0%)
Gastrointestinal disorders
Ulcerative colitis flare requiring admission	2/42 (4.8%)	2	0/70 (0%)	0
Hepatobiliary disorders
Pancreatitis	1/42 (2.4%)	1	0/70 (0%)	0
Musculoskeletal and connective tissue disorders
Facet join injection	1/42 (2.4%)	1	0/70 (0%)	0
Other (Not Including Serious) Adverse Events
	Golimumab Induction Therapy		Golimumab Maintenance Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.