Clinical trial NCT04156984: Comparison of Two Different Golimumab Dosing Regimens for Ulcerative Colitis
Official title: Exposure-response of Golimumab During Maintenance in Ulcerative Colitis: An Exploratory Pharmacokinetics/Pharmacodynamics Comparison of Different Dose Regimens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ulcerative Colitis
Keywords: 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
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
First posted: 2019-11-08
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Endoscopic outcome
timeFrame: 50 weeks
Secondary outcomes:
measure: Clinical outcome
timeFrame: 50 weeks
measure: Association of golimumab through levels and Anti-golimumab antibodies development on endoscopic and clinical outcome.
timeFrame: 50 weeks
Other outcomes:
measure: Measurement of physical, social, and emotional status with The Short Inflammatory Bowel Disease Questionnaire.
timeFrame: 50 weeks
measure: Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.0.
timeFrame: 50 weeks.
Locations:
city: Celje
country: Slovenia
facility: General hospital Celje, Department of Gastoenterology
city: Izola
country: Slovenia
facility: General hospital Izola, Department of Internal medicine
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana, Department of Gastroenterology
city: Maribor
country: Slovenia
facility: University Medical Centre Maribor, Department of Gastoenterology
Study officials:
affiliation: University Medical Centre Ljubljana
name: David Drobne, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Centre Ljubljana
name: Borut Štabuc, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.