Comparison of Two Different Golimumab Dosing Regimens for Ulcerative Colitis

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

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.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Golimumab Prefilled Syringe

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 4

Contacts and Locations

Study Locations

• Slovenia
  • Celje, Slovenia, 3000
    • General hospital Celje, Department of Gastoenterology
  • Izola, Slovenia, 6310
    • General hospital Izola, Department of Internal medicine
  • Ljubljana, Slovenia, 1000
    • University Medical Centre Ljubljana, Department of Gastroenterology
  • Maribor, Slovenia, 2000
    • University Medical Centre Maribor, Department of Gastoenterology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Study arm; 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; See arm description
Other: Control arm; 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; See arm description

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of physical, social, and emotional status with The Short Inflammatory Bowel Disease Questionnaire.	The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) is a health-related quality of life (HRQoL) tool measuring physical, social, and emotional status (score 10-70, poor to good HRQoL). The questionnaire will be answered at week 0, week 6, week 14, week 26, week 38, week 50.	50 weeks
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.0.	Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0.	50 weeks.

Collaborators and Investigators

• Sponsor: David Drobne
• Investigators: Principal Investigator: David Drobne, MD, PhD, University Medical Centre Ljubljana; Study Director: Borut Štabuc, MD, PhD, University Medical Centre Ljubljana

Publications and helpful links

General Publications

• Stefanovic S, Detrez I, Compernolle G, Brouwers E, Sever N, Stabuc B, Smrekar N, Kurent T, Novak G, Kozelj M, Ferrante M, Gils A, Drobne D. Endoscopic remission can be predicted by golimumab concentrations in patients with ulcerative colitis treated with the changed label. Eur J Gastroenterol Hepatol. 2021 Jan;33(1):54-61. doi: 10.1097/MEG.0000000000001843.

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2021
• Primary Completion (Actual): June 18, 2024
• Study Completion (Actual): June 18, 2024

Study Registration Dates

• First Submitted: October 24, 2019
• First Submitted That Met QC Criteria: November 5, 2019
• First Posted (Actual): November 8, 2019

Study Record Updates

• Last Update Posted (Actual): July 30, 2024
• Last Update Submitted That Met QC Criteria: July 26, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Therapeutic drug monitoring; Golimumab; Personalized medicine; Inflammatory bowel disease; Pharmacodynamics; Mucosal healing; Reactive dose optimisation; Proactive dose optimisation; Golimumab concentration; Comparisons of European with US label
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Tumor Necrosis Factor Inhibitors; Golimumab
• Other Study ID Numbers: 2019-001G

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes