Ulcerative Colitis
Conditions
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
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.
Interventions
DRUGGolimumab Prefilled Syringe
See arm description
Sponsors
David Drobne
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endoscopic outcome | 50 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical outcome | 50 weeks | 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). |
| Association of golimumab through levels and Anti-golimumab antibodies development on endoscopic and clinical outcome. | 50 weeks | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.0. | 50 weeks. | Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0. |
| Measurement of physical, social, and emotional status with The Short Inflammatory Bowel Disease Questionnaire. | 50 weeks | 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. |
Countries
Slovenia
Outcome results
None listed