A Non-inferiority Study on Dose Reduction of Adalimumab in Psoriasis Patients Who Are Overtreated

NCT ID: NCT05683054

Last Updated: 2023-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

19 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-11

Study Completion Date

2022-08-22

Brief Summary

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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

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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,

Conditions

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Psoriasis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A prospective, single blinded, randomized, non-inferiority study
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
PASI and IGA score will be performed by a blinded and independent physician.

Study Groups

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Standard dosing group

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).

Group Type ACTIVE_COMPARATOR

Venapuncture

Intervention Type PROCEDURE

Blood samples will be collected to determine the serum trough levels and anti-drug antibodies of adalimumab

Dermatology Life Quality Index (DLQI)

Intervention Type OTHER

The impact of the disease on the patient will be assessed using the dermatology life quality index (DLQI).

EQ-5D-5L questionnaire

Intervention Type OTHER

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.

Dried blood spot sampling

Intervention Type PROCEDURE

A subset of patients will sample additionally by using dried blood sampling after the first drug injection post-inclusion.

Dose tapering group

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.

Group Type ACTIVE_COMPARATOR

Dose tapering of adalimumab in patients with supratheurapeutic serum trough levels

Intervention Type BIOLOGICAL

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).

Venapuncture

Intervention Type PROCEDURE

Blood samples will be collected to determine the serum trough levels and anti-drug antibodies of adalimumab

Dermatology Life Quality Index (DLQI)

Intervention Type OTHER

The impact of the disease on the patient will be assessed using the dermatology life quality index (DLQI).

EQ-5D-5L questionnaire

Intervention Type OTHER

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.

Dried blood spot sampling

Intervention Type PROCEDURE

A subset of patients will sample additionally by using dried blood sampling after the first drug injection post-inclusion.

Interventions

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Dose tapering of adalimumab in patients with supratheurapeutic serum trough levels

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 BIOLOGICAL

Venapuncture

Blood samples will be collected to determine the serum trough levels and anti-drug antibodies of adalimumab

Intervention Type PROCEDURE

Dermatology Life Quality Index (DLQI)

The impact of the disease on the patient will be assessed using the dermatology life quality index (DLQI).

Intervention Type OTHER

EQ-5D-5L questionnaire

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 OTHER

Dried blood spot sampling

A subset of patients will sample additionally by using dried blood sampling after the first drug injection post-inclusion.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. Participants must be \>18 years of age.
2. 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.
3. 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)
4. 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
5. 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.
6. Participants must avoid prolonged sun exposure and use of tanning booths or other ultraviolet light sources during study.
7. 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

1. Participants who have currently a predominant nonplaque forms of psoriasis (eg. Erythrodermic, guttate, pustular)
2. 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
3. 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
4. Participants who have known allergies, hypersensitivity or intolerance to adalimumab or its excipients
5. Participants who have any malignancy or have a history of malignancy
6. Participants who are unable or unwilling to undergo multiple venapunctures
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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KU Leuven

OTHER

Sponsor Role collaborator

University Hospital, Ghent

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jo Lambert, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Ghent

Locations

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University Hospital

Ghent, , Belgium

Site Status

Countries

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Belgium

Other Identifiers

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TDM-ADA2019

Identifier Type: -

Identifier Source: org_study_id

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