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

January 18, 2024 updated by: Radboud University Medical Center

Dose Reduction of the New Generation Biologicals (IL17 and IL23 Inhibitors) in Psoriasis: A Pragmatic, Multicentre, Randomized, Controlled, Non-inferiority Study - BeNeBio Study

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Estimated)

244

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Brussels, Belgium
        • ULB Erasme
      • Gent, Belgium, 9000
        • Ghent University Hospital
      • Ghent, Belgium
        • AZ Maria Middelares
      • Ghent, Belgium
        • AZ St Lucas
      • Leuven, Belgium
        • UZ Leuven
      • Liège, Belgium
        • CHU Liège
      • Louvain, Belgium
        • UCL Saint Luc
      • Maldegem, Belgium
        • Dermatologie Maldegem
      • Almelo, Netherlands
        • Ziekenhuisgroep Twente
      • Bergen Op Zoom, Netherlands
        • Bravis hospital
      • Breda, Netherlands
        • Amphia Hospital
      • Doetinchem, Netherlands
        • Slingeland Hospital
      • Eindhoven, Netherlands
        • Catharina Hospital
      • Groningen, Netherlands
        • UMC Groningen
      • Maastricht, Netherlands
        • Maastricht UMC
      • Nijmegen, Netherlands, 6500HB
        • Radboudumc
      • Rotterdam, Netherlands
        • Erasmus MC
      • Utrecht, Netherlands
        • UMC Utrecht
      • Veldhoven, Netherlands
        • Máxima Medisch Centrum

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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.
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 Names:
  • Cosentyx
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 Names:
  • Taltz
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 Names:
  • Kyntheum
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 Names:
  • Tremfya
Maintenance/normal dose is 150 mg every 12 weeks. First dose reduction step: 150mg/18 weeks. Second dose reduction step: 150mg/24 weeks.
Other Names:
  • Skyrizi
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 Names:
  • Ilumetri
Maintenance/normal dose is 320 mg/8 weeks. First dose reduction step: 320 mg/12 weeks. Second dose reduction step: 320 mg/16 weeks.
Other Names:
  • Bimzelx
Active Comparator: Normal dose
Patients will continue treatment with the normal/maintenance dose of the biologicals.
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 Names:
  • Cosentyx
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 Names:
  • Taltz
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 Names:
  • Kyntheum
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 Names:
  • Tremfya
Maintenance/normal dose is 150 mg every 12 weeks. First dose reduction step: 150mg/18 weeks. Second dose reduction step: 150mg/24 weeks.
Other Names:
  • Skyrizi
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 Names:
  • Ilumetri
Maintenance/normal dose is 320 mg/8 weeks. First dose reduction step: 320 mg/12 weeks. Second dose reduction step: 320 mg/16 weeks.
Other Names:
  • Bimzelx

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Non-inferiority of the incidence proportion of persistent flares (Psoriasis Area and Severity Index (PASI) >5 for ≥ 3 months).
Time Frame: 18 months
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Whether participants will have successful DR after 12 and 18 months, defined as using a lower dose than the normal dose and PASI ≤ 5.
Time Frame: 18 months
Definition of successful dose reduction: lower dose than the normal dose and PASI≤ 5.
18 months
Psoriasis disease activity, measured with the Psoriasis Area and Severity Index (PASI) at each 3-monthly study visit.
Time Frame: 18 months
18 months
Dermatology-related quality of life as measured with the Dermatology Life Quality Index (DLQI) at each 3-montly study visit.
Time Frame: 18 months
18 months
Whether participants will have short disease flares throughout the study period (18 months), defined as a PASI > 5 at one time point.
Time Frame: 18 months
18 months
Whether other anti-psoriatic medication will be initiated in participants during the study period (18 months).
Time Frame: 18 months
18 months
Whether participants will have serious adverse events (SAE) and adverse events of special interest (AEoSI) during the study period.
Time Frame: 18 months
AEoSI include, but are not limited to, infections, malignancies, and joint complaints or new-onset psoriatic arthritis.
18 months
Drug trough levels of each included drug, measured in blood serum samples which will be collected from participants at each 3-montly time point.
Time Frame: 18 months
18 months
Anti-drug antibody levels of each included drug, measured in blood serum samples which will be collected from participants at each 3-montly time point.
Time Frame: 18 months
18 months
Utilities, derived from EuroQoL 5 Dimensions (EQ-5D-5L) questionnaires, which will be measured at each 3-montly time point.
Time Frame: 18 months
Utility scores will be used to calculate quality adjusted life years (QALYs) which are used to determine cost-effectiveness of DR.
18 months
Health status of participants, assessed by using the Short Form 36 (SF-36) version 2 questionnaire at every 3-monthly time point.
Time Frame: 18 months
18 months
Volumes of care, as measured with the iMTA Medical Consumption Questionnaire (MCQ) at each 3-monthly time point. Scores will be used to calculate direct medicals costs and non-medical costs.
Time Frame: 18 months
18 months
Loss of productivity and presenteeism of participants, as measured with the iMTA Productivity Cost Questionnaire (PCQ) at each 3-monthly time point. Scores will be used to calculate direct medicals costs and non-medical costs.
Time Frame: 18 months
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Elke de Jong, MD, PhD, Radboud University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 20, 2020

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

March 20, 2020

First Submitted That Met QC Criteria

April 6, 2020

First Posted (Actual)

April 9, 2020

Study Record Updates

Last Update Posted (Actual)

January 19, 2024

Last Update Submitted That Met QC Criteria

January 18, 2024

Last Verified

September 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

  • 80-85200-98-18562
  • 2019-004230-42 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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