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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
Sponsor:
Information provided by (Responsible Party):
D.L.P. Baeten, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary:

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

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)


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Study Type : Observational
Estimated Enrollment : 16 participants
Observational Model: Other
Time Perspective: Prospective
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

Resource links provided by the National Library of Medicine

Drug Information available for: Ustekinumab

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)




Primary Outcome Measures :
  1. 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.


Other Outcome Measures:
  1. 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


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

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.

Information from the National Library of Medicine

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


Contacts
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Contact: Dominique LP Baeten, MD PhD Prof 00312056 ext 67765 d.l.baeten@amc.uva.nl
Contact: Henriette MY de Jong, MD 00312056 ext 67765 h.m.dejong@amc.uva.nl

Locations
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Netherlands
Academic Medical Center Amsterdam Recruiting
Amsterdam, Noord-Holland, Netherlands, 1105AZ
Contact: Henriette MY de Jong, MD    00312056 ext 67765    h.m.dejong@amc.uva.nl   
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
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Principal Investigator: Dominique LP Baeten, MD PhD Prof Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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Responsible Party: D.L.P. Baeten, Prof. Dr. D.L.P. Baeten, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT03565042     History of Changes
Other Study ID Numbers: AMC_50218_MoA anti-p40
First Posted: June 21, 2018    Key Record Dates
Last Update Posted: June 21, 2018
Last Verified: June 2018
Keywords provided by D.L.P. Baeten, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Arthritis, Psoriatic
Mechanism of Action
Ustekinumab
anti-p40
anti-IL23/Il12 p40
Additional relevant MeSH terms:
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Arthritis
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Ustekinumab
Dermatologic Agents