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Comparison of Two Different Golimumab Dosing Regimens for Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT04156984
Recruitment Status : Not yet recruiting
First Posted : November 8, 2019
Last Update Posted : March 25, 2020
Sponsor:
Information provided by (Responsible Party):
David Drobne, University Medical Centre Ljubljana

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.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: Golimumab Prefilled Syringe Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Exposure-response of Golimumab During Maintenance in Ulcerative Colitis: An Exploratory Pharmacokinetics/Pharmacodynamics Comparison of Different Dose Regimens
Estimated Study Start Date : May 2020
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Golimumab

Arm Intervention/treatment
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

Control arm

Subjects treated according to current European Label (2019) based on body weight:

  1. <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.
  2. ≥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




Primary Outcome Measures :
  1. Endoscopic outcome [ Time Frame: 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 Outcome Measures :
  1. Clinical outcome [ Time Frame: 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).

  2. Association of golimumab through levels and Anti-golimumab antibodies development on endoscopic and clinical outcome. [ Time Frame: 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 Outcome Measures:
  1. Measurement of physical, social, and emotional status with The Short Inflammatory Bowel Disease Questionnaire. [ Time Frame: 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.

  2. Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.0. [ Time Frame: 50 weeks. ]
    Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04156984


Contacts
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Contact: David Drobne, MD, PhD +38615221552 david.drobne@kclj.si
Contact: Sanjo Finderle, MD +38615222639 sanjo.finderle@kclj.si

Locations
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Slovenia
General hospital Celje, Department of Gastoenterology
Celje, Slovenia, 3000
Contact: Renata Šibli, MD,    +38634233441    renata.sibli@guest.arnes.si   
Principal Investigator: Renta Šibli, MD         
General hospital Izola, Department of Internal medicine
Izola, Slovenia, 6310
Contact: Tamara Marušič, MD    +38656606551    tamara.marusic@sb-izola.si   
Principal Investigator: Tamara Marušič, MD         
University Medical Centre Ljubljana, Department of Gastroenterology
Ljubljana, Slovenia, 1000
Contact: David Drobne, MD, PhD    +38615221552    david.drobne@kclj.si   
Contact: Sanjo Finderle, MD    +38615222639    sanjo.finderle@kclj.si   
Principal Investigator: David Drobne, MD, PhD         
Principal Investigator: Borut Štabuc, MD, PhD         
Sub-Investigator: Sanjo Finderle, MD         
University Medical Centre Maribor, Department of Gastoenterology
Maribor, Slovenia, 2000
Contact: Andreja Ocepek, MD    +38623212348    andreja.ocepek@ukc-mb.si   
Principal Investigator: Andreja Ocepek, MD         
Sponsors and Collaborators
David Drobne
Investigators
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Principal Investigator: David Drobne, MD, PhD University Medical Centre Ljubljana
Study Director: Borut Štabuc, MD, PhD University Medical Centre Ljubljana
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Responsible Party: David Drobne, Principal investigator, University Medical Centre Ljubljana
ClinicalTrials.gov Identifier: NCT04156984    
Other Study ID Numbers: 2019-001G
First Posted: November 8, 2019    Key Record Dates
Last Update Posted: March 25, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by David Drobne, University Medical Centre Ljubljana:
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
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Golimumab
Tumor Necrosis Factor Inhibitors
Anti-Inflammatory Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs