This study has been transitioned to CTIS with ID 2024-510903-12-00 check the CTIS register for the current data. Primary objective:Identify pre-treatment profiles with integrated clinical, transcriptomic, metabolomic, proteomic, flow cytometric, and…
ID
Source
Brief title
Condition
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters/endpoints:
-Minimal Disease Activity (MDA) at week 16
-Baseline molecular network profile (based on the composite systems medicine
analysis)
Secondary outcome
-change (50%) in the molecular network before treatment as compared to after
(week 4 and 16) treatment
-change in composite clinical disease activity scores (MDA, ACR(20,50,70)
response, DAS28) at week 16.
-change in individual clinical parameters that make up the composite scores
(i.e. PASI score (reduction of 50%, 75%, 90%), joint count, CRP, ESR,
QOL-measures) at week 16
Background summary
Rationale: Psoriatic arthritis is currently treated by an array of drugs, yet
the best choice of drug for the individual patient in both the early phase of
the disease and the later phase of disease is unknown. As a consequence,
patients undergo a *trial and error* approach to treatments, delaying time to
treatment response and negatively impacting quality of life.
Study objective
This study has been transitioned to CTIS with ID 2024-510903-12-00 check the CTIS register for the current data.
Primary objective:
Identify pre-treatment profiles with integrated clinical, transcriptomic,
metabolomic, proteomic, flow cytometric, and imaging data that predict response
to treatment with tofacitinib, in DMARD-naïve and DMARD non-responsive PsA
patients.
Secondary objectives:
- Compare clinical efficacy of treatment with tofacitinib, methotrexate and
etanercept in DMARD-naïve and DMARD-non responsive patients with active PsA
- Determine (medication specific) molecular mechanisms predicting and
underlying clinical response to tofacitinib in comparison to methotrexate and
etanercept in active PsA
Study design
Study design: Multicentre, open label, randomized phase III clinical trial in
active psoriatic arthritis patients. In arm 1, patients are naïve to csDMARD
and will be randomized to receive either methotrexate monotherapy or
tofacitinib monotherapy. In arm 2, patients are being treated with methotrexate
background therapy yet still have active disease and will be randomized to
receive additional etanercept or additional tofacitinib. Treatment failure will
result in therapy switch (combination therapy in Arm1; cross-over in Arm2).
Biological studies will be performed throughout the study.
Intervention
Intervention (if applicable):
-Treatment with either standard of care drugs (methotrexate, etanercept) or the
phase III interventional study drug tofacitinib (orally, 5mg twice per day)
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness:
-Imaging studies (MRI, PET-CT, X-rays), low risk
-Venapuncture (3x), low risk
-Clinical examinations and questionnaires (BL,4, and 16 weeks), low burden
-Therapeutic intervention with either standard of care (methotrexate or
etanercept) or the interventional study drug (tofacitinib): moderate risk.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
• Age 18-75 years old
• Meets CASPAR criteria for psoriatic arthritis
• Disease duration of at least 8 weeks
• Evidence of active arthritis based upon >=2 swollen joints and >=2 tender joints
• Subjects are to discontinue active psoriasis treatment prior to being
enrolled in the study.
• Inclusion criteria arm 1:
o No history of csDMARD use or bDMARD therapy use
• Inclusion criteria arm 2:
o Current use of methotrexate, sulfasalazine or leflunomide on the highest
tolerated dosage and on a stable dosage for at least 4 weeks prior to
randomization. Highest dosage accepted respectively are max <=25mg/wk, 20mg/day
and 3000mg/day.
o *History of use of max. 1 bDMARD prior to inclusion is allowed, except:
- Prior use of etanercept
- Primary failure (total non-response at start) on other TNFi (adalimumab,
golimumab, infliximab, certolizumab). Patients that have had a loss of response
on their first TNFi are allowed to participate.
o No history of tsDMARD therapy use (JAKi, abatacept)
Exclusion criteria
• Currently have pustular psoriasis only
• Participation in other studies involving investigational drug(s) (Phases 1-4)
within 4 weeks before the current study begins and/or during study
participation. Participation in any observational studies during study
participation.
• Pregnant females, breastfeeding females, females of child-bearing potential
not using highly effective contraception or not agreeing to continue highly
effective contraception for at least one ovulatory cycle after last dose of
investigational product or females planning pregnancy. Women of childbearing
potential must test negative for pregnancy prior to enrolment in this study.
• Current or recent history of a severe, progressive or uncontrolled renal,
hepatic, hematological, gastrointestinal, metabolic (including
hypercholersterolemia), endocrine, pulmonary, cardiovascular, or neurologic
disease.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-510903-12-00 |
| EudraCT | EUCTR2017-003900-28-NL |
| CCMO | NL63439.041.17 |