Comparison of Two Different Golimumab Dosing Regimens for Ulcerative Colitis

Study Overview
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Brief Summary
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Partial response or loss of response to golimumab is observed in a significant proportion of patients started on golimumab for active ulcerative colitis. The current dosing regimen in European Union is based on patients' body weight as maintenance treatment for patients with ≥ 80 kg is 100 mg q4 weeks and for patients with <80 kg 50 mg q4 weeks. The investigators recent observations in a golimumab pharmacokinetics study of 24 patients however, show large interindividual variations in golimumab trough concentrations. Furthermore, it seems that patients with continuous response have higher golimumab trough levels at several time points during treatment compared to patients who lose response. Higher induction/maintenance dose of golimumab increases golimumab trough levels, therefore it is likely that higher induction/maintenance dose of golimumab would increase efficacy of golimumab treatment.

Detailed Description
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Partial response or loss of response to golimumab is observed in a significant proportion of patients started on golimumab for active ulcerative colitis. The current dosing regimen in European Union is based on patients' body weight as maintenance treatment for patients with ≥ 80 kg is 100 mg q4 weeks and for patients with <80 kg 50 mg q4 weeks. The investigators recent observations in a golimumab pharmacokinetics study of 24 patients however, show large interindividual variations in golimumab trough concentrations. Furthermore, it seems that patients with continuous response have higher golimumab trough levels at several time points during treatment compared to patients who lose response. Higher induction/maintenance dose of golimumab increases golimumab trough levels, therefore it is likely that higher induction/maintenance dose of golimumab would increase efficacy of golimumab treatment.

Official Title
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Exposure-response of Golimumab During Maintenance in Ulcerative Colitis: An Exploratory Pharmacokinetics/Pharmacodynamics Comparison of Different Dose Regimens

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Golimumab Prefilled Syringe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed ulcerative colitis Exclusion Criteria: Active tuberculosis or other opportunistic bacterial, viral and fungal infections History of moderate to severe heart failure (NYHA III/IV), and potential risk of congestive heart failure Pregnancy History of allergic reactions to sorbitol (E420), L-histidine, L-histidine monohydrochloride monohydrate, polysorbate80, water for injections.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Study arm<br>Subjects treated with optimized dose of golimumab, irrespective of weight: golimumab 200 mg sc, followed by 100 mg sc at week 2 and then 100 mg sc q4 weeks. In case of disease flare: discontinuation of drug. | Drug: Golimumab Prefilled Syringe<br>* See arm description<br>|
| Other: Control arm<br>Subjects treated according to current European Label (2019) based on body weight: <80kg: golimumab 200 mg sc, followed by 100 mg sc at week 2 and then 50 mg sc q4wk. In case of disease flare (defined as PRO-2 ≥1): dose optimization to 100 mg sc q4wk starting at week 6 or at any time during first year. ≥80kg: golimumab 200 mg sc, followed by 100 mg sc at week 2 and then 100 mg sc q4wk. In case of disease flare (defined as PRO-2 ≥1): discontinuation of drug. | Drug: Golimumab Prefilled Syringe<br>* See arm description<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endoscopic outcome | Number of participants with mucosal healing at week 14 and week 50 on flexible rectosigmoidoscopy (recorded and assessed centrally by blinded reader if possible). Mucosal healing is defined as Mayo endoscopic score 0 or 1. | 50 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical outcome | Number of participants in clinical remission at week 14, week 26, week 38 and week 50. Clinical remission is defined as PRO-2 (Patient-Reported Outcome) score 0 (no rectal bleeding and no diarrhea/altered bowel habit). | 50 weeks | 
| Association of golimumab through levels and Anti-golimumab antibodies development on endoscopic and clinical outcome. | Measurement of golimumab through levels. Blood withdrawals will be preformed at prespecified time points in all patients: week 0, week 2, week 4, week 6, week 10, week 14, week 26, week 38 and week 50. Measurement of Anti-golimumab antibodies development. Blood withdrawals will be preformed at prespecified time points in all patients: week 2, week 4, week 6, week 10, week 14, week 26, week 38 and week 50. | 50 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Pharmacodynamics, Safety, Golimumab, Reactive dose optimisation, Proactive dose optimisation, Golimumab concentration, Mucosal healing, Therapeutic drug monitoring, Inflammatory bowel disease, Personalized medicine, Comparisons of European with US label