Dose Tapering Study of Adalimumab in Psoriasis

Phase 4

Terminated

• Conditions: Psoriasis Vulgaris
• Interventions: Procedure: Venapuncture; Procedure: Dried blood spot; Drug: Dose reduction

• Registration Number: NCT04028713
• Lead Sponsor: University Hospital, Ghent

Brief Summary

The optimal therapeutic serum trough level (Ctrough) of adalimumab was defined between 3,5 and 7,0 µg/ml in patients with plaque type psoriasis. An adalimumab Ctrough above this therapeutic range did not add clinical response. Based on this therapeutic window, the introduction of dose adjustments based on Ctroughs (therapeutic drug monitoring) will be further validated in a prospective randomized-controlled trial. Here, we aim to determine whether, in patients with a good clinical response and supratherapeutic adalimumab Ctroughs, dose reduction is able to maintain favorable clinical outcome.

Detailed Description

Patients will be included after signing informed consent and randomized in either a standard dose arm or a concentration based arm based on prior Ctrough measurements. In the concentration based arm, dosing frequency will be lowered to once every 3 weeks. If patients still have supratherapeutic Ctroughs of adalimumab, these patients will continue adalimumab self-administration every 4 weeks. In the standard based arm, patients will continue on standard dosing schedule. During each study visit blood will be taken in order to quantify Ctroughs. In addition, Psoriasis Area and Severity Index (PASI) and Investigator's Global Assessment (IGA) score will be evaluated by a physician. Patients complete the Dermatology Life Quality Index (DLQI) and European quality of life EQ-5D 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.

Study Timeline

• Study First Submitted: 2019-07-19
• Study First Submitted QC: 2019-07-22
• Study First Posted: 2019-07-23
• Status Verified: 2019-12
• Study Start: 2021-02-16
• Primary Completion: 2022-03-22
• Study Completion: 2022-03-22
• Last Update Submitted: 2022-12-19
• Last Update Posted: 2022-12-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

1. Participants must have a clinical or histological diagnosis of chronic plaque-type psoriasis for at least 6 months prior to inclusion
2. Participants must have a stable disease during maintenance on adalimumab (absolute PASI < 3)
3. Participants are not allowed to use topical steroids from 7 days before randomization until the end of the study (week 48).
4. 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 form of psoriasis
2. Participants who are pregnant, nursing or planning a pregnancy while enrolled in the study or within 12 weeks after receiving the last administration of study intervention
3. Participants who are unable or unwilling to undergo multiple venapunctures
4. Participants who are treated according to a different dosing schedule than standard dosing of adalimumab (regular dose regimen every 2 weeks; 40 mg)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard dosing group	Venapuncture	Patients will continue to receive adalimumab according to the standard dosing schedule.
Dose tapering group	Venapuncture	Adalimumab dosing frequency will be lowered in patients who have supratherapeutic serum trough levels of adalimumab.
Standard dosing group	Dried blood spot	Patients will continue to receive adalimumab according to the standard dosing schedule.
Dose tapering group	Dried blood spot	Adalimumab dosing frequency will be lowered in patients who have supratherapeutic serum trough levels of adalimumab.
Dose tapering group	Dose reduction	Adalimumab dosing frequency will be lowered in patients who have supratherapeutic serum trough levels of adalimumab.

Primary Outcome Measures

Name	Time	Method
Clinical response	Week 0- Week 48	The proportion of patients in each group in clinical remission (absolute PASI \< 2) at year 1 after optimization

Secondary Outcome Measures

Name	Time	Method
The proportion of patients in each group with anti-drug antibodies (ADA) against adalimumab.	Week 0- Week 48
Relapse	Week 0- Week 48	The proportion of patients in each group who relapses (defined as the need for dose escalation (not in the standard based dosing arm))
The proportion of patients in each group with serum trough levels of adalimumab within the optimal interval.	Week 0- Week 48

Trial Locations

Locations (7)

University Hospital Ghent; 🇧🇪 Ghent, East-Flanders, Belgium

Private practice Dermatology; 🇧🇪 Maldegem, East-Flanders, Belgium

University Hospital Leuven; 🇧🇪 Leuven, Vlaams-Brabant, Belgium

AZ Sint-Jan; 🇧🇪 Brugge, West-Vlaanderen, Belgium

AZ Maria Middelares; 🇧🇪 Ghent, East-Flanders, Belgium

AZ Sint-Lucas; 🇧🇪 Ghent, East-Flanders, Belgium

AZ Delta Rembert; 🇧🇪 Torhout, West-Flanders, Belgium