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

NCT05683054 | Completed Phase 4

• 1 other identifier: TDM-ADA2019
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Psoriasis

Outcome Measures

Primary Outcomes (2)

• Clinical response

  The proportion of patients in each group in clinical remission (absolute PASI \< 2) at year 1 after optimization

  1 year after inclusion

• 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)

  Sampling at home on days 0, 3, 5, 7, 14, 21, 28, 35, 42 and 49 after adalimumab administration

Secondary Outcomes (6)

• Relapse

  1 year after inclusion

• Serum trough levels of adalimumab within the optimal therapeutic window

  1 year after inclusion

• Anti- drug antibodies against adalimumab

  1 year after inclusion

• Cost-effectiveness of adalimumab dose tapering

  1 year after inclusion

• Quality adjusted life years

  1 year after inclusion

Study Arms (2)

Standard dosing group

ACTIVE COMPARATOR

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).

Procedure: Venapuncture; Other: Dermatology Life Quality Index (DLQI); Other: EQ-5D-5L questionnaire; Procedure: Dried blood spot sampling

Dose tapering group

ACTIVE COMPARATOR

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.

Biological: Dose tapering of adalimumab in patients with supratheurapeutic serum trough levels; Procedure: Venapuncture; Other: Dermatology Life Quality Index (DLQI); Other: EQ-5D-5L questionnaire; Procedure: Dried blood spot sampling

Interventions

Dose tapering of adalimumab in patients with supratheurapeutic serum trough levels 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).

Dose tapering group

Venapuncture PROCEDURE

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

Dose tapering group; Standard dosing group

Dermatology Life Quality Index (DLQI) OTHER

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

Dose tapering group; Standard dosing group

EQ-5D-5L questionnaire 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.

Dose tapering group; Standard dosing group

Dried blood spot sampling PROCEDURE

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

Dose tapering group; Standard dosing group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Ghent: lead
• KU Leuven: collaborator

Study Sites (1)

University Hospital

Ghent, 9000, Belgium

Location

MeSH Terms

Conditions

Psoriasis

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Jo Lambert, Prof. Dr.

  University Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: PASI and IGA score will be performed by a blinded and independent physician.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A prospective, single blinded, randomized, non-inferiority study

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 12, 2023
• Study Start: August 11, 2020
• Primary Completion: March 22, 2022
• Study Completion: August 22, 2022
• Last Updated: January 12, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)