Back to resultsA Non-inferiority Study on Dose Reduction of Adalimumab in Psoriasis Patients Who Are Overtreated
Primary Purpose
Psoriasis
Status
Completed
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Dose tapering of adalimumab in patients with supratheurapeutic serum trough levels
Venapuncture
Dermatology Life Quality Index (DLQI)
EQ-5D-5L questionnaire
Dried blood spot sampling
Sponsored by
About this trial
This is an interventional treatment trial for Psoriasis
Eligibility Criteria
Inclusion Criteria: Participants must be >18 years of age. Participants must have a diagnosis of chronic plaque-type psoriasis for at least 6 months (with or without PsA), prior to the first administration of study intervention. Participant must remain on a highly effective method of birth control during the study or during the entire treatment with adalimumab (whether with is longer) Participants are considered eligible according to the following TB screening criteria: Have no history of latent or active TB before screening Have no signs or symptoms suggestive for active TB upon medical history and/or physical examination Have had no recent close contact with a person with active TB Participants must agree not to receive a live virus or live bacterial vaccination at least 3 months (or longer as indicated in the package insert of the relevant vaccine) prior to the first administration of study intervention (except for varicella and MMR vaccines), during the study, or within 3 months after the last administration of study intervention. Participants must avoid prolonged sun exposure and use of tanning booths or other ultraviolet light sources during study. Participants must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study. Exclusion Criteria: Participants who have currently a predominant nonplaque forms of psoriasis (eg. Erythrodermic, guttate, pustular) Participants who are pregnant, nursing or planning a pregnancy or fathering a child while enrolled in the study or within 12 weeks after receiving the last administration of study intervention Participants who have received, or are expected to receive, any live virus or bacterial vaccination (with the exception of varicella or MMR vaccines) within 3 months (or longer as indicated in the package insert of the relevant vaccine) prior to the first administration of study intervention, during the study, or within 12 weeks after the last administration of study intervention Participants who have known allergies, hypersensitivity or intolerance to adalimumab or its excipients Participants who have any malignancy or have a history of malignancy Participants who are unable or unwilling to undergo multiple venapunctures
Sites / Locations
- University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Standard dosing group
Dose tapering group
Arm Description
In the standard based arm, patients will continue to receive adalimumab according to the standard dosing schedule of 40 mg every other week (maintenance phase).
In the dose tapering arm, adalimumab dosing frequency will be lowered to 40 mg every 3 weeks in patients who have supratherapeutic serum trough levels of adalimumab at three consecutive measurements.
Outcomes
Primary Outcome Measures
Clinical response
The proportion of patients in each group in clinical remission (absolute PASI < 2) at year 1 after optimization
Validation of adalimumab dried blood spots
Optimization of extraction protocol for adalimumab serum trough levels and anti-adalimumab antibody concentrations derived from dried blood spots (DBS)
Secondary Outcome Measures
Relapse
The proportion of patients in each group who relapse (defined as the need for dose escalation (not in the standard based dosing arm))
Serum trough levels of adalimumab within the optimal therapeutic window
The proportion of patients in each group with serum trough levels (STL) of adalimumab within the optimal interval (3.5µg/ml -7 µg/ml)
Anti- drug antibodies against adalimumab
The proportion of patients in each group with anti-drug antibodies (ADA) against adalimumab (ADA positivity)
Cost-effectiveness of adalimumab dose tapering
Quality adjusted life years
Identify relevant parameters for PK-PD modeling
- Recording of demographic parameters during disease course monitored at baseline and at every visit (reflected by incidence, prevalence, mortality, standardized comorbidity incidence ratios and associations/risk factors).
Full Information
NCT ID
NCT05683054
First Posted
December 21, 2022
Last Updated
January 5, 2023
Sponsor
University Hospital, Ghent
Collaborators
KU Leuven
1. Study Identification
Unique Protocol Identification Number
NCT05683054
Brief Title
A Non-inferiority Study on Dose Reduction of Adalimumab in Psoriasis Patients Who Are Overtreated
Official Title
A Non-inferiority Study on Dose Reduction of Adalimumab in Psoriasis Patients Who Are Overtreated
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
August 11, 2020 (Actual)
Primary Completion Date
March 22, 2022 (Actual)
Study Completion Date
August 22, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Ghent
Collaborators
KU Leuven
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Recently, the optimal therapeutic serum trough level range of adalimumab was defined between 3,5 and 7,0 µg/ml in patients with plaque type psoriasis. An adalimumab serum through level above this therapeutic range did not add to clinical response. Based on this therapeutic window, the introduction of dose adjustments based on serum trough levels (therapeutic drug monitoring) will be further validated in a prospective controlled trial. Here, we aim to determine whether, in patients with a good clinical response and supratherapeutic adalimumab STLs, dose reduction based on therapeutic drug monitoring (TDM) is able to maintain the initial clinical outcome.
Detailed Description
In this study we investigate whether dose reduction of adalimumab in patients with supratherapeutic adalimumab Ctrough levels is non-inferior to standard dosing of adalimumab.
Before randomization, 3 subsequent evaluations of adalimumab Ctroughs will be executed. Patients will be included after signing informed consent and randomized if 2/3 subsequent measurements during screening show supratherapeutic Ctrough levels. Time point of randomization is considered baseline (week 0). PASI calculation will be performed by a blinded and independent physician.
In the concentration based arm, dosing frequency will be lowered to 40 mg every 3 weeks (33% reduction). In case of persistent supratherapeutic Ctroughs, a 50% dose reduction will be applied from week 12 onwards. In the standard based arm, patients will continue on standard dosing schedule of 40 mg every other week.
During each study visit PASI and IGA score will be evaluated by an independent and blinded physician and adverse events, and concomitant medications will be evaluated by a member of the study team. Ctrough is quantified at each visit; and anti-drug antibodies concentrations only if subtherapeutic concentrations are observed. Patients complete the Dermatology Life Quality Index (DLQI) and EuroQol-5D-5L instrument at each visit.
In addition, in a subset of patients in each treatment arm, additional sampling will be collected by dried blood spot sampling in order to build a PK(PD) model for adalimumab,
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psoriasis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
A prospective, single blinded, randomized, non-inferiority study
Masking
Outcomes Assessor
Masking Description
PASI and IGA score will be performed by a blinded and independent physician.
Allocation
Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Standard dosing group
Arm Type
Active Comparator
Arm Description
In the standard based arm, patients will continue to receive adalimumab according to the standard dosing schedule of 40 mg every other week (maintenance phase).
Arm Title
Dose tapering group
Arm Type
Active Comparator
Arm Description
In the dose tapering arm, adalimumab dosing frequency will be lowered to 40 mg every 3 weeks in patients who have supratherapeutic serum trough levels of adalimumab at three consecutive measurements.
Intervention Type
Biological
Intervention Name(s)
Dose tapering of adalimumab in patients with supratheurapeutic serum trough levels
Intervention Description
In the dose tapering arm, adalimumab dosing frequency will be lowered to 40 mg every 3 weeks in patients who have supratherapeutic serum trough levels of adalimumab (33% reduction). If patients still have a good clinical response and supratherapeutic adalimumab serum trough levels, will be further tapered to a dose regimen of 1 subcutaneous injection (40mg) every 4 weeks (50% dose reduction).
Intervention Type
Procedure
Intervention Name(s)
Venapuncture
Intervention Description
Blood samples will be collected to determine the serum trough levels and anti-drug antibodies of adalimumab
Intervention Type
Other
Intervention Name(s)
Dermatology Life Quality Index (DLQI)
Intervention Description
The impact of the disease on the patient will be assessed using the dermatology life quality index (DLQI).
Intervention Type
Other
Intervention Name(s)
EQ-5D-5L questionnaire
Intervention Description
The EQ-5D-5L which is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments will be assessed.
Intervention Type
Procedure
Intervention Name(s)
Dried blood spot sampling
Intervention Description
A subset of patients will sample additionally by using dried blood sampling after the first drug injection post-inclusion.
Primary Outcome Measure Information:
Title
Clinical response
Description
The proportion of patients in each group in clinical remission (absolute PASI < 2) at year 1 after optimization
Time Frame
1 year after inclusion
Title
Validation of adalimumab dried blood spots
Description
Optimization of extraction protocol for adalimumab serum trough levels and anti-adalimumab antibody concentrations derived from dried blood spots (DBS)
Time Frame
Sampling at home on days 0, 3, 5, 7, 14, 21, 28, 35, 42 and 49 after adalimumab administration
Secondary Outcome Measure Information:
Title
Relapse
Description
The proportion of patients in each group who relapse (defined as the need for dose escalation (not in the standard based dosing arm))
Time Frame
1 year after inclusion
Title
Serum trough levels of adalimumab within the optimal therapeutic window
Description
The proportion of patients in each group with serum trough levels (STL) of adalimumab within the optimal interval (3.5µg/ml -7 µg/ml)
Time Frame
1 year after inclusion
Title
Anti- drug antibodies against adalimumab
Description
The proportion of patients in each group with anti-drug antibodies (ADA) against adalimumab (ADA positivity)
Time Frame
1 year after inclusion
Title
Cost-effectiveness of adalimumab dose tapering
Time Frame
1 year after inclusion
Title
Quality adjusted life years
Time Frame
1 year after inclusion
Title
Identify relevant parameters for PK-PD modeling
Description
- Recording of demographic parameters during disease course monitored at baseline and at every visit (reflected by incidence, prevalence, mortality, standardized comorbidity incidence ratios and associations/risk factors).
Time Frame
1 year after inclusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants must be >18 years of age.
Participants must have a diagnosis of chronic plaque-type psoriasis for at least 6 months (with or without PsA), prior to the first administration of study intervention.
Participant must remain on a highly effective method of birth control during the study or during the entire treatment with adalimumab (whether with is longer)
Participants are considered eligible according to the following TB screening criteria:
Have no history of latent or active TB before screening
Have no signs or symptoms suggestive for active TB upon medical history and/or physical examination
Have had no recent close contact with a person with active TB
Participants must agree not to receive a live virus or live bacterial vaccination at least 3 months (or longer as indicated in the package insert of the relevant vaccine) prior to the first administration of study intervention (except for varicella and MMR vaccines), during the study, or within 3 months after the last administration of study intervention.
Participants must avoid prolonged sun exposure and use of tanning booths or other ultraviolet light sources during study.
Participants must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
Exclusion Criteria:
Participants who have currently a predominant nonplaque forms of psoriasis (eg. Erythrodermic, guttate, pustular)
Participants who are pregnant, nursing or planning a pregnancy or fathering a child while enrolled in the study or within 12 weeks after receiving the last administration of study intervention
Participants who have received, or are expected to receive, any live virus or bacterial vaccination (with the exception of varicella or MMR vaccines) within 3 months (or longer as indicated in the package insert of the relevant vaccine) prior to the first administration of study intervention, during the study, or within 12 weeks after the last administration of study intervention
Participants who have known allergies, hypersensitivity or intolerance to adalimumab or its excipients
Participants who have any malignancy or have a history of malignancy
Participants who are unable or unwilling to undergo multiple venapunctures
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jo Lambert, Prof. Dr.
Organizational Affiliation
University Ghent
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Non-inferiority Study on Dose Reduction of Adalimumab in Psoriasis Patients Who Are Overtreated
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