Dose Reduction of IL17 and IL23 Inhibitors in Psoriasis (BeNeBio)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04340076 |
|
Recruitment Status :
Recruiting
First Posted : April 9, 2020
Last Update Posted : December 6, 2022
|
Sponsor:
Radboud University Medical Center
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 Medical Center
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 Drug: Bimekizumab | Phase 4 |
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 (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 |
| 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 Drug: Bimekizumab 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 Name: Bimzelx |
|
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 Drug: Bimekizumab 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 Name: Bimzelx |
Primary Outcome Measures :
- Non-inferiority of the incidence proportion of persistent flares (Psoriasis Area and Severity Index (PASI) >5 for ≥ 3 months). [ Time Frame: 18 months ]
Secondary Outcome Measures :
- 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.
- Psoriasis disease activity, measured with the Psoriasis Area and Severity Index (PASI) at each 3-monthly study visit. [ Time Frame: 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 ]
- 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 ]
- Whether other anti-psoriatic medication will be initiated in participants during the study period (18 months). [ Time Frame: 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.
- 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 ]
- 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 ]
- 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.
- 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 ]
- 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 ]
- 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 ]
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| 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
| Contact: Juul van den Reek, MD, PhD | 0031243613724 | juul.vandenreek@radboudumc.nl |
Locations
Show 19 study locations
Sponsors and Collaborators
Radboud University Medical Center
ZonMw: The Netherlands Organisation for Health Research and Development
Belgium Health Care Knowledge Centre
University Hospital, Ghent
Investigators
| Principal Investigator: | Elke de Jong, MD, PhD | Radboud University Medical Center |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Radboud University Medical Center |
| 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: | December 6, 2022 |
| Last Verified: | September 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| 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 Medical Center:
|
skin diseases skin diseases (papulosquamous) biologicals |
IL17 inhibitors IL23 inhibitors dose reduction |
Additional relevant MeSH terms:
|
Psoriasis Skin Diseases, Papulosquamous Skin Diseases |
Ixekizumab Brodalumab Dermatologic Agents |