Clinical trial NCT04610476: Impact of Tapering Immunosuppressants on Maintaining Minimal Disease Activity in Adult Subjects With Psoriatic Arthritis
Official title: A Prospective, Randomized, Controlled, Open Label, Assessor-blinded, Parallel-group Phase III Clinical Trial to Evaluate the Impact of Tapering Systemic Immunosuppressive Therapy in a Treat-to-target Approach on Maintaining Minimal Disease Activity in Adult Subjects With Psoriatic Arthritis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Psoriatic Arthritis
Withdrawal
Reduction
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
First posted: 2020-10-30
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The rationale for this study is to investigate whether in psoriatic arthritis (PsA) patients in stable remission a reduction or complete discontinuation of immunosuppressive therapy can be achieved in a treat-to-target approach while maintaining in remission. Due to the lack of reliable data that answers the question of how to safely reduce medication in which patients, this study will test a pragmatic treatment algorithm that can be applied in clinical practice and that offers a gradual reduction with escape strategies in order to facilitate the maintenance of remission.


Eligibility criteria: Inclusion Criteria:

* Written informed consent obtained from the subject
* Understanding of study procedures and willingness to abide by all procedures during the course of the study.
* Adult subject; age range 18-≤75 years
* Male or female subject
* Diagnosis of PsA according to CASPAR criteria
* Disease status "MDA" for at least 6 months
* Subject should have been treated without alterations of therapy (fixed dose and drug) for at least 6 months with one or more of the following drugs:

  i. csDMARD Leflunomid (e.g. Arava), Sulfasalazin (e.g. Azulfidine RA, Pleon RA), Methotrexate (e.g. Lantarel, Metex) AND/OR ii. bDMARD/tsDMARD: Etanercept (e.g. Enbrel, Erelzi, Benepali), Adalimumab (e.g. Humira, Amgevita, Imraldi, Hyrimoz), Infliximab (e.g. Remicade, Zessly, Inflectra), Golimumab (Simponi), Certolizumab (Cimzia), Abatacept (Orencia), Apremilast (Otezla), Ustekinumab (Stelara), Secukinumab (Cosentyx), Ixekizumab (Taltz), Tofacitinib (Xeljanz) AND/OR (c) glucocorticoids (≤5mg prednisolone equivalent).
* Women of childbearing potential must be using a highly effective method of birth control.
* Male subjects using an adequate contraceptive method at the investigator's discretion.

Exclusion Criteria:

* Diagnosis of any other rheumatological/ immunological disease such as rheumatoid arthritis, SLE, PSS, MCTD, M. Behcet or M. Wegener
* Concomitant florid (not sufficiently adjusted under treatment) autoimmune disease such as autoimmune hepatitis or Hashimoto's disease
* Use of any inadmissible medication (e.g. current treatment with DMARDs other than mentioned above or drugs under development)
* Treatment with systemic glucocorticoids (daily dose \>5mg prednisolone equivalent) during the last 6 months before randomization. Intra-articular or entheseal injections of glucocorticoids do not constitute an exclusion criterion
* Malignant disease currently under oncological treatment or history of a recent malignancy with moderate or high risk of relapse within 5 years prior to Screening
* Existence of another disease including the presence of laboratory abnormalities which, at the discretion of the investigator, would result in a disproportionate risk to the patient concerned or confounds the ability to interpret data from the study
* Any anti-inflammatory (excluding NSAIDs) or immunosuppressive therapy for other reasons than PsA or psoriasis during the last 3 months before Screening
* Nursing mother or pregnant woman as verified by a positive pregnancy test
* Known hypersensitivity to the IMPs or any of their formulation ingredients
* Subject who is imprisoned or is lawfully kept in an Institution
* Employee or direct relative of an employee of the study site or the Sponsor
* Participation in an interventional clinical study with an IMP within the last 4 weeks before Screening
* Previous participation in this clinical study
* Planned extended stay outside the region which prevents compliance with the visit schedule

Primary outcomes:
measure: Presence of MDA (minimal disease activity) 12 months after baseline.
timeFrame: 12 months
Secondary outcomes:
measure: Key secondary endpoint: PASDAS (Psoriatic Arthritis Disease Activity Score)
timeFrame: 12 months
measure: Key secondary endpoint: DAPSA (Disease Activity in PSoriatic Arthritis)
timeFrame: 12 months
measure: Key secondary endpoint: CPDAI (Composite Psoriatic Disease Activity Index)
timeFrame: 12 months
measure: Number of swollen and tender joints
timeFrame: 12 months
measure: Number of tender entheseal points: SPARCC (Spondyloarthritis Consortium of Canada)
timeFrame: 12 months
measure: Number of tender entheseal Points: LEI (Leeds Enthesitis Index)
timeFrame: 12 months
measure: Number of tender entheseal Points: MASES (Maastricht Ankylosing Spondylitis Enthesitis Score)
timeFrame: 12 months
measure: Dactylitis counts
timeFrame: 12 months
measure: Activity of psoriasis: PASI (Psoriasis Area and Severity Index)
timeFrame: 12 months
measure: Activity of psoriasis: BSA (body surface area)
timeFrame: 12 months
measure: Activity of axial Involvement: BASDAI (Disease Activity of Ankylosing Spondylitis)
timeFrame: 12 months
measure: Quality of life and health/disability: PsAID-12 (Psoriatic Arthritis Impact of Disease)
timeFrame: 12 months
measure: Quality of life and health/disability: HAQ-DI (Stanford Health Assessment Questionnaire Disability Index)
timeFrame: 12 months
measure: Quality of life and health/disability: DLQI (Dermatology Life Quality Index)
timeFrame: 12 months
measure: Quality of life and health/disability: ASQoL (Ankylosing Spondylitis Quality of Life)
timeFrame: 12 months
measure: Quality of life and health/Disability: SF-36 (Short Form Health)
timeFrame: 12 months
measure: Pain (VAS)
timeFrame: 12 months
measure: Proportion of patients with loss of MDA within 12 months after baseline
timeFrame: 12 months
measure: Proportion of patients with loss of MDA within 24 months after baseline
timeFrame: 24 months
measure: Time to loss of MDA
timeFrame: 12 months
measure: Time needed to restore MDA after readjustment of the DMARD therapy in subjects who lost MDA within the intervention period
timeFrame: 12 months
measure: Biomarker levels
timeFrame: 24 months
measure: Intervention-related events within the observation period of 24 months after baseline
timeFrame: 24 months
measure: AE (Adverse Event)
timeFrame: 12 months
measure: AR (Adverse Reaction)
timeFrame: 12 months
measure: SAE (Serious Adverse Event)
timeFrame: 12 months
measure: SAR (Serious Adverse Reaction)
timeFrame: 12 months
measure: SUSAR (Suspected Unexpected Serious Adverse Reaction)
timeFrame: 12 months
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bavaria
Study officials:
References: