Mechanism of Action of Ustekinumab in Psoriatic Arthritis (MoA anti-p40)

June 20, 2018 updated by: D.L.P. Baeten, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Mechanism of Action Study of Ustekinumab Treatment in Psoriatic Arthritis: Impact on Cellular and Molecular Pathways of Synovial Inflammation and Tissue Remodeling

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Rationale:

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.

Objectives:

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.

Study design:

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.

Study population:

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

Enrollment (Anticipated)

16

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1105AZ
        • Recruiting
        • Academic Medical Center Amsterdam
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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. In total 16 patients will be included.

Description

Inclusion Criteria:

  • Male and female patients age > 18 years diagnosed with Psoriatic Arthritis according to the CASPAR criteria
  • Patient for whom the treating physician has decided to prescribe in the usual manner: Ustekinumab (Stelara) (45mg/ injection, given on week 0, 4, and every 12 weeks thereafter)
  • Active disease defined by ≥1 swollen and ≥ 1 tender joint, and at least 1 swollen knee or ankle joint at baseline

Exclusion Criteria:

  • Contraindications for needle-arthroscopy such as joint replacement (in the affected knee or ankle joint).
  • Use of any investigational drug and/or devices within 4 weeks of baseline, or a period of 5 half-lives of the investigational drug, whichever is longer.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Other
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
MoA ustekinumab
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.
Procedure: Arthroscopy
Arthroscopy of swollen joint (ankle/knee)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Cellular and molecular changes of the synovium of samples obtained at week 0 compared with week 12 and week 24.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
week 0 compared with week 12 and week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Investigators

  • Principal Investigator: Dominique LP Baeten, MD PhD Prof, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 8, 2015

Primary Completion (Anticipated)

October 1, 2018

Study Completion (Anticipated)

November 1, 2018

Study Registration Dates

First Submitted

March 1, 2016

First Submitted That Met QC Criteria

June 20, 2018

First Posted (Actual)

June 21, 2018

Study Record Updates

Last Update Posted (Actual)

June 21, 2018

Last Update Submitted That Met QC Criteria

June 20, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AMC_50218_MoA anti-p40

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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