Clinical trial NCT04028713: Dose Tapering Study of Adalimumab in Psoriasis
Official title: A Non-inferiority Study on Dose Reduction of Adalimumab in Psoriasis Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Psoriasis Vulgaris
Keywords: Therapeutic drug monitoring
Psoriasis
Adalimumab
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: KU Leuven
name: University Ghent
First posted: 2019-07-23
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized non-inferiority study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Clinical response
timeFrame: Week 0- Week 48
Secondary outcomes:
measure: The proportion of patients in each group with serum trough levels of adalimumab within the optimal interval.
timeFrame: Week 0- Week 48
measure: The proportion of patients in each group with anti-drug antibodies (ADA) against adalimumab.
timeFrame: Week 0- Week 48
measure: Relapse
timeFrame: Week 0- Week 48
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: AZ Maria Middelares
state: East-Flanders
city: Ghent
country: Belgium
facility: AZ Sint-Lucas
state: East-Flanders
city: Ghent
country: Belgium
facility: University Hospital Ghent
state: East-Flanders
city: Maldegem
country: Belgium
facility: Private practice Dermatology
state: East-Flanders
city: Leuven
country: Belgium
facility: University Hospital Leuven
state: Vlaams-Brabant
city: Torhout
country: Belgium
facility: AZ Delta Rembert
state: West-Flanders
city: Brugge
country: Belgium
facility: AZ Sint-Jan
state: West-Vlaanderen
Study officials:
affiliation: University Hospital, Ghent
name: Jo Lambert, Prof, dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Soenen R, Stove C, Capobianco A, De Schutter H, Dobbelaere M, Mahjor T, Follens M, Lambert J, Grine L. Promising Tools to Facilitate the Implementation of TDM of Biologics in Clinical Practice. J Clin Med. 2022 May 26;11(11):3011. doi: 10.3390/jcm11113011.