Dose Tapering Study of Adalimumab in Psoriasis

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

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.

Study Overview

• Status: Terminated
• Conditions: Psoriasis Vulgaris
• Intervention / Treatment: Procedure: Venapuncture; Procedure: Dried blood spot; Drug: Dose reduction

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 Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • East-Flanders
    • Ghent, East-Flanders, Belgium, 9000
      • University Hospital Ghent
    • Ghent, East-Flanders, Belgium, 9000
      • AZ Maria Middelares
    • Ghent, East-Flanders, Belgium, 9000
      • AZ Sint-Lucas
    • Maldegem, East-Flanders, Belgium, 9990
      • Private practice Dermatology
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • University Hospital Leuven
  • West-Flanders
    • Torhout, West-Flanders, Belgium, 8820
      • AZ Delta Rembert
  • West-Vlaanderen
    • Brugge, West-Vlaanderen, Belgium, 8000
      • AZ Sint-Jan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard dosing group; Patients will continue to receive adalimumab according to the standard dosing schedule.	Procedure: Venapuncture; Blood samples will be collected to determine the serum trough levels and anti-drug antibodies of adalimumab.; Procedure: Dried blood spot; A subset of patients will sample additionally by using the dried blood sampling technique.
Experimental: Dose tapering group; Adalimumab dosing frequency will be lowered in patients who have supratherapeutic serum trough levels of adalimumab.	Procedure: Venapuncture; Blood samples will be collected to determine the serum trough levels and anti-drug antibodies of adalimumab.; Procedure: Dried blood spot; A subset of patients will sample additionally by using the dried blood sampling technique.; Drug: Dose reduction; Adalimumab dosing frequency will be lowered in patients who have supratherapeutic serum trough levels of adalimumab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	The proportion of patients in each group in clinical remission (absolute PASI < 2) at year 1 after optimization	Week 0- Week 48

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: KU Leuven; University Ghent
• Investigators: Principal Investigator: Jo Lambert, Prof, dr, University Hospital, Ghent

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2021
• Primary Completion (Actual): March 22, 2022
• Study Completion (Actual): March 22, 2022

Study Registration Dates

• First Submitted: July 19, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (Actual): July 23, 2019

Study Record Updates

• Last Update Posted (Actual): December 21, 2022
• Last Update Submitted That Met QC Criteria: December 19, 2022
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Psoriasis; Therapeutic drug monitoring; Adalimumab
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: BIOLOPTIM-ADA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No