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Dose Reduction of IL17 and IL23 Inhibitors in Psoriasis (BeNeBio)

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ClinicalTrials.gov Identifier: NCT04340076
Recruitment Status : Recruiting
First Posted : April 9, 2020
Last Update Posted : July 7, 2021
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
Belgium Health Care Knowledge Centre
University Hospital, Ghent
Information provided by (Responsible Party):
Radboud University

Brief Summary:
The main objective of this study is to investigate whether controlled dose reduction of IL17 or IL23 inhibiting biologics is not inferior compared to usual care in psoriasis patients. Therefore, a pragmatic, multicentre, randomized, controlled, non-inferiority study will be carried out.

Condition or disease Intervention/treatment Phase
Psoriasis Psoriasis Vulgaris Drug: Secukinumab Drug: Ixekizumab Drug: Brodalumab Drug: Guselkumab Drug: Risankizumab Drug: Tildrakizumab Phase 4

Detailed Description:

Rationale: Biologics are very effective treatments for psoriasis. Research indicated that the dose of TNFα-blocking biologics can be reduced in a proportion of patients. Safety profiles can improve and costs can be reduced if the reduction of the dose is successful. Recently, the newest generation of biologics entered the market: interleukin (IL) 17 and IL23 inhibitors. It is not yet known whether dose reduction of these agents is possible, and to what extent they can be reduced. The timely investigation of the possibilities for dose reduction of new biologics is therefore important.

Objectives: The primary goal is to investigate whether controlled dose reduction of IL17 or IL23 inhibiting biologics is not inferior compared to usual care. This is measured by comparing the proportion of long-term disease flares between the two groups (dose reduction group versus usual care group). Secondary goals are: determining the proportion of patients with successful dose reduction, clinical effectiveness measured with the Psoriasis Area and Severity score (PASI) score, Dermatology Life Quality Index (DLQI) scores, predictors for successful dose reduction, safety, and cost-effectiveness of dose reduction. Pharmacokinetic (PK) analysis will be performed for modeling.

Study design: a multicenter, practice-oriented, pragmatic, randomized, controlled, non-inferiority study.

Study population: Patients treated with the newest generation of biologics (IL17 or IL23 inhibitors), with long-term stable low disease activity at a normal dose. A total of 244 patients will be randomized (2:1) to dose reduction or continuation of usual care.

Intervention: Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 244 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A multicentre, pragmatic, randomized, controlled, non-inferiority trial. Patients will be randomized 2:1 to dose reduction and usual care.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dose Reduction of the New Generation Biologicals (IL17 and IL23 Inhibitors) in Psoriasis: A Pragmatic, Multicentre, Randomized, Controlled, Non-inferiority Study - BeNeBio Study
Actual Study Start Date : August 20, 2020
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis

Arm Intervention/treatment
Experimental: Dose reduction
Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low.
Drug: Secukinumab
Maintenance/normal dose is 300 mg/4 weeks. First dose reduction step: 300 mg/6 weeks. Second dose reduction step: 300 mg/8 weeks.
Other Name: Cosentyx

Drug: Ixekizumab
Maintenance/normal dose is 80 mg/4 weeks. First dose reduction step: 80 mg/6 weeks. Second dose reduction step: 80 mg/8 weeks
Other Name: Taltz

Drug: Brodalumab
Maintenance/normal dose is 210 mg/2 weeks. First dose reduction step: 210 mg/3 weeks. Second dose reduction step: 210 mg/4 weeks.
Other Name: Kyntheum

Drug: Guselkumab
Maintenance/normal dose is 100 mg/8 weeks. First dose reduction step: 100 mg/12 weeks. Second dose reduction step: 100 mg/16 weeks.
Other Name: Tremfya

Drug: Risankizumab
Maintenance/normal dose is 150 mg every 12 weeks. First dose reduction step: 150mg/18 weeks. Second dose reduction step: 150mg/24 weeks.
Other Name: Skyrizi

Drug: Tildrakizumab
Maintenance/normal dose is 100 mg or 200 mg every 12 weeks. First dose reduction step: 100 mg or 200 mg/18 weeks. Second dose reduction step: 100 mg or 200 mg/24 weeks.
Other Name: Ilumetri

Active Comparator: Normal dose
Patients will continue treatment with the normal/maintenance dose of the biologicals.
Drug: Secukinumab
Maintenance/normal dose is 300 mg/4 weeks. First dose reduction step: 300 mg/6 weeks. Second dose reduction step: 300 mg/8 weeks.
Other Name: Cosentyx

Drug: Ixekizumab
Maintenance/normal dose is 80 mg/4 weeks. First dose reduction step: 80 mg/6 weeks. Second dose reduction step: 80 mg/8 weeks
Other Name: Taltz

Drug: Brodalumab
Maintenance/normal dose is 210 mg/2 weeks. First dose reduction step: 210 mg/3 weeks. Second dose reduction step: 210 mg/4 weeks.
Other Name: Kyntheum

Drug: Guselkumab
Maintenance/normal dose is 100 mg/8 weeks. First dose reduction step: 100 mg/12 weeks. Second dose reduction step: 100 mg/16 weeks.
Other Name: Tremfya

Drug: Risankizumab
Maintenance/normal dose is 150 mg every 12 weeks. First dose reduction step: 150mg/18 weeks. Second dose reduction step: 150mg/24 weeks.
Other Name: Skyrizi

Drug: Tildrakizumab
Maintenance/normal dose is 100 mg or 200 mg every 12 weeks. First dose reduction step: 100 mg or 200 mg/18 weeks. Second dose reduction step: 100 mg or 200 mg/24 weeks.
Other Name: Ilumetri




Primary Outcome Measures :
  1. Non-inferiority of (cumulative incidence of) persistent flares (Psoriasis Area and Severity Index (PASI) >5 for ≥ 3 months). [ Time Frame: 18 months ]

Secondary Outcome Measures :
  1. Numbers and proportions of patients with a successful dose decrease after 12 and after 18 months [ Time Frame: 18 months ]
    Definition of successful dose reduction: lower dose than the normal dose and PASI≤ 5.

  2. Correlation with time and PASI (Psoriasis Area and Severity Index) in both groups in patients with dose reduction vs. usual care at 18 months. [ Time Frame: 18 months ]
  3. Correlation with time and DLQI (Dermatology Life Quality Index) in both groups in patients with dose reduction vs. usual care at 18 months. [ Time Frame: 18 months ]
  4. Absolute PASI at month 12 and 18 in patients with dose reduction vs. usual care. [ Time Frame: 18 months ]
  5. Absolute DLQI at month 12 and 18 in patients with dose reduction vs. usual care. [ Time Frame: 18 months ]
  6. Incidence of short disease flares after 18 months in patients with dose reduction vs. usual care. [ Time Frame: 18 months ]
    Definition of short disease flare: PASI>5 at 1 time point

  7. Proportion of patients with initiation of other antipsoriatic medication during the study (e.g. intensive topical therapies, methotrexate, acitretin) in patients with dose reduction vs. usual care. [ Time Frame: 18 months ]
  8. Predictors for successful dose decrease. [ Time Frame: 18 months ]
    Candidate predictors include general patient and treatment characteristics.

  9. Absolute numbers and proportions of serious adverse events (SAE) and adverse events of interest (AEoSI) in patients with dose reduction vs. usual care. [ Time Frame: 18 months ]
  10. (Course of) and (changes in) drug trough levels of each included drug. [ Time Frame: 18 months ]
    Drug trough levels will be determined to gain insight in the clearance of the biologics during dose reduction and relation to successful dose reduction.

  11. (Course of) and (changes in) anti-drug antibody levels of each included drug. [ Time Frame: 18 months ]
    Anti-drug antibody levels will be determined to gain insight in the clearance of the biologics during dose reduction and relation to successful dose reduction.

  12. (Changes in) health-status (SF-36) in patients with dose reduction vs. usual care. [ Time Frame: 18 months ]
    Short Form Health Survey (SF-36v2) questionnaire will be used to measure health status. Questionnaires will be administered every 3 months.

  13. (Changes in) quality-adjusted life-years (EQ-5D-5L) in patients with dose reduction vs. usual care. [ Time Frame: 18 months ]
    The EQ-5D-5L is a health-related quality of life questionnaire which can be used to derive utilities from. Questionnaires will be administered every 3 months.

  14. (Changes in) volumes of care (iMTA MCQ) in patients with dose reduction vs. usual care. [ Time Frame: 18 months ]
    The iMTA Medical Consumption Questionnaire (MCQ) measures all relevant health care related costs. Questionnaires will be administered every 3 months.

  15. (Changes in) loss of productivity and presenteeism (iMTA PCQ) in patients with dose reduction vs. usual care. [ Time Frame: 18 months ]
    The iMTA Productivity Cost Questionnaire (PCQ) measures loss of productivity due to illness or recovery in patients below the age of 65 years based on patient reported absences from paid (or unpaid) labor. Questionnaires will be administered every 3 months.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Plaque psoriasis (primarily)
  • Treatment for at least 6 months with IL23 or IL17 inhibitor in a normal dose (dose advised by the label)
  • PASI≤ 5 at inclusion and in previous 6 months (if no PASI scores are available, it should be clear from the patient record that psoriasis was clear/almost clear in previous 6 months).
  • DLQI ≤ 5 at inclusion

Exclusion Criteria:

  • Another indication than plaque psoriasis as the main indication for biologic use (e.g. patient receives biologic for rheumatoid arthritis as the main indication).
  • Concomitant use of systemic immunosuppressants other than methotrexate or acitretin (e.g. prednisone, cyclosporine etc).
  • Severe comorbidities with short life-expectancy (e.g. metastasized tumor).
  • Presumed inability to follow the study protocol.

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): NCT04340076


Contacts
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Contact: Juul van den Reek, MD, PhD 0031243613724 juul.vandenreek@radboudumc.nl
Contact: Lara van der Schoot, MD 0031243613724 lara.vanderschoot@radboudumc.nl

Locations
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Belgium
Ghent University Hospital Recruiting
Gent, Belgium, 9000
Contact: Jo Lambert, MD, PhD         
Netherlands
Radboudumc Recruiting
Nijmegen, Netherlands, 6500HB
Contact: Juul van den Reek, MD, PhD         
Sponsors and Collaborators
Radboud University
ZonMw: The Netherlands Organisation for Health Research and Development
Belgium Health Care Knowledge Centre
University Hospital, Ghent
Investigators
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Principal Investigator: Elke de Jong, MD, PhD Radboud University
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT04340076    
Other Study ID Numbers: 80-85200-98-18562
2019-004230-42 ( EudraCT Number )
First Posted: April 9, 2020    Key Record Dates
Last Update Posted: July 7, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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 Radboud University:
skin diseases
skin diseases (papulosquamous)
biologicals
IL17 inhibitors
IL23 inhibitors
dose reduction
Additional relevant MeSH terms:
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Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Ixekizumab
Brodalumab
Dermatologic Agents