Mechanism of Action of Ustekinumab in Psoriatic Arthritis (MoA anti-p40)
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|ClinicalTrials.gov Identifier: NCT03565042|
Recruitment Status : Recruiting
First Posted : June 21, 2018
Last Update Posted : June 21, 2018
The purpose of this study is to determine the mechanism of action on target tissue level of ustekinumab treatment in psoriatic arthritis patients.
Patients who are planning to start treatment with anti-p40 therapy (ustekinumab) will be included in the trial.
At week 0, 12 and 24 peripheral blood, synovial tissue and skin will be obtained and analysed with different techniques to assess the effect of the therapy on inflammatory pathways.
|Condition or disease||Intervention/treatment|
|Arthritis, Psoriatic||Procedure: Arthroscopy|
The overall aim of the study is to determine which downstream cellular and molecular pathways involved in psoriatic arthritis (PsA) pathogenesis are modulated by Interleukine 23/Interleukine12 P40 subunit (IL23/12 P40) blockade. As we have ample evidence that relevant disease-specific pathways are found in the primary target tissues, in particular in synovial tissue obtained from peripheral joints, but not in peripheral blood, we will strongly focus on this compartment by obtaining paired biopsies before and after treatment.
The primary objective is to assess the effect of IL23/12 P40 blockade on cellular en molecular pathways involved in PsA disease in the synovium, in the synovial fluid and peripheral blood.
The secondary objective is to compare which cellular/molecular disease pathways are affected by IL23/12 P40 blockade and not by tumour necrosis factor (TNF) blockade and thereby identify molecular biomarkers which may help to determine which patients may benefit from this treatment in comparison with anti-TNF treatment.
Single centre, 24-week open-label study in subjects with clinically active peripheral psoriatic arthritis receiving treatment with ustekinumab.
Synovial biopsies will be obtained from patients before and after 12 and 24 weeks of treatment with ustekinumab.
Patients with a diagnosis of psoriatic arthritis according to the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria with at least one swollen knee or ankle joint who are planning to receive treatment with ustekinumab at the outpatient clinic. In total 16 patients will be included.
Intervention: Blood withdrawal and mini-arthroscopies at different timepoints.
Main study parameters/endpoints:
Primary study parameters/outcome of the study:
• Changes in the synovial cellular infiltrate and molecular pathways influenced between baseline and week 12/ week24
Secondary study parameters/outcome of the study:
• Comparison of the synovial molecular changes induced by anti-p40 with the changes induced by anti-TNF (analysed in historical samples in a similar patient population and study setting)
|Study Type :||Observational|
|Estimated Enrollment :||16 participants|
|Official Title:||Mechanism of Action Study of Ustekinumab Treatment in Psoriatic Arthritis: Impact on Cellular and Molecular Pathways of Synovial Inflammation and Tissue Remodeling|
|Actual Study Start Date :||December 8, 2015|
|Estimated Primary Completion Date :||October 2018|
|Estimated Study Completion Date :||November 2018|
Patients with a diagnosis of psoriatic arthritis according to the CASPAR criteria with at least one swollen knee or ankle joint who are planning to receive treatment with ustekinumab at the outpatient clinic. An arthroscopy will be done in the swollen knee/ankle at week 0, 12 and 24.
Arthroscopy of swollen joint (ankle/knee)
- Biological effect of treatment on synovium obtained via arthroscopy from a swollen knee or ankle. [ Time Frame: Cellular and molecular changes of the synovium of samples obtained at week 0 compared with week 12 and week 24. ]Cellular and molecular changes of the synovium.
- biological effect of anti TNF v.s. anti IL23/IL12 p40 on synovium obtained from a swollen knee or ankle. [ Time Frame: week 0 compared with week 12 and week 24 ]molecular and cellular changes affected by anti IL23/IL12 p40 and not by anit TNF therapy.
Biospecimen Retention: Samples With DNA
- synovial tissue
- synovial tissue both obtained at timepoint 0 (before first ustekinumab injection) ,wk 12, and wk24 after starting treatment
- peripheral blood obtained at wk 0, wk 4, 8, 12 and 24
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03565042
|Contact: Dominique LP Baeten, MD PhD Prof||00312056 ext email@example.com|
|Contact: Henriette MY de Jong, MD||00312056 ext firstname.lastname@example.org|
|Academic Medical Center Amsterdam||Recruiting|
|Amsterdam, Noord-Holland, Netherlands, 1105AZ|
|Contact: Henriette MY de Jong, MD 00312056 ext 67765 email@example.com|
|Principal Investigator:||Dominique LP Baeten, MD PhD Prof||Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|