Impact of Tapering Immunosuppressants on Maintaining Minimal Disease Activity in Adult Subjects With Psoriatic Arthritis

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

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.

Study Overview

Study Type

Interventional

Enrollment (Anticipated)

270

Phase

  • Phase 3

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

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 to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control group
Individual previous stable glucocorticoid/DMARD therapy is continued
Experimental: Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Prednisolone oral 1-5 mg/day
Other Names:
  • Prednisolone generic drugs
Sulfasalazine oral 2 x 1000 mg/day
Other Names:
  • Azulfidine
Leflunomide oral 20 mg/day
Other Names:
  • Arava
Methotrexate oral > 10 - 30 mg/ week/ 10 mg/week/ 7.5 mg/week; s.c. 15 (7.5 -25) mg/week
Other Names:
  • Lantarel, Metex
Tofacitinib oral 2 x 5 mg/day/ 1 x 5 mg/day/11 mg/day
Other Names:
  • Xeljanz
Apremilast oral 2 x 30 mg/day/1 x 30 mg/day
Other Names:
  • Otezla
Etanercept s.c. 2 x 25 mg /week OR 1 x 50 mg/week
Other Names:
  • Enbrel, Erelzi, Benepali
Adalimumab s.c. 40 mg every 2 weeks
Other Names:
  • Humira, Amgevita, Imraldi, Hyrimoz
Infliximab i.v. 5 mg/kg BW every 8 weeks
Other Names:
  • Remicade, Zessly, Inflectra
Certolizumab pegol s.c. 1x 200 mg every 2 weeks/1x400 mg every 4 weeks
Other Names:
  • Cimzia
Golimumab s.c. 1x 50 mg every 4 weeks
Other Names:
  • Simponi
Abatacept s.c. 1x125 mg/week OR Abatacept i.v. 500-1000mg (adapted to BW) every 4 weeks
Other Names:
  • Orencia
Secukinumab s.c.1x 150 mg OR 1x 300 mg every 4 weeks
Other Names:
  • Cosentyx
Ixekizumab s.c. 1x 80 mg every 4 weeks
Other Names:
  • Taltz
Ustekinumab s.c. Maintenance dose 1x45 mg every 12 weeks
Other Names:
  • Stelara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of MDA (minimal disease activity) 12 months after baseline.
Time Frame: 12 months

The MDA status comprises the assessment of different domains of PsA, consisting of the following individual components:

  • swollen and tender joint count
  • tender entheseal point count
  • skin involvement (PASI)patient self-assessment of pain (VAS)
  • global disease activity status
  • subject's self-assessment of functional ability using Stanford Health Assessment Questionnaire disability index, (HAQ-DI)

MDA is defined as the presence of 5 of the following 7 criteria:

  1. tender joint count ≤1
  2. swollen joint count ≤1
  3. tender entheseal point count ≤1 (means: remission)
  4. PASI ≤1 OR body surface area (BSA) ≤3%
  5. patient pain VAS ≤15
  6. patient global activity VAS ≤20
  7. HAQ-DI ≤0.5
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Key secondary endpoint: PASDAS (Psoriatic Arthritis Disease Activity Score)
Time Frame: 12 months

The PASDAS is a composite disease activity index (range 0-10) for psoriatic arthritis (PsA) incorporating seven domains: patient and physician global activity VAS scores, tender and swollen joint counts (arthritis), dactylitis, enthesitis (Leeds), health-related QoL (SF-36), and CRP level. PASDAS has demonstrated to have a better discriminate capacity in distinguishing high and low disease activity. The PASDAS is computed by the following equation: PASDAS = (((0, 18 ∗

∗√(PhGA) + 0.159 ∗ ∗√(PtGA) - 0.253 ∗ ∗√(SF36 -PCS) + 0.101 ∗ lognat(SJC66 + 1)) + 0.048 ∗ lognat(SJC68 +1)) + 0.23 ∗ lognat (Leeds enthesitis index + 1)) + 0.37 ∗lognat (tender dactylitis count + 1) + 0.102 ∗ lognat (CRP +1) + 2 ∗ 1.5.

12 months
Key secondary endpoint: DAPSA (Disease Activity in PSoriatic Arthritis)
Time Frame: 12 months
The DAPSA score determines changes in the disease activity of subjects diagnosed with PsA. DAPSA is a composite score which is calculated from the sum of: number of tender joints (0-68), number of swollen joints (0-66, hips are not taken into account), CRP (mg/dl), subject's assessment of global status of disease activity using VAS (0-10) and patient's self-assessment of pain using VAS (0-10). A value of the composite score DAPSA 0-≤ 4 marks remission, 5-14 marks low, 15-28 moderate and >28 high disease activity
12 months
Key secondary endpoint: CPDAI (Composite Psoriatic Disease Activity Index)
Time Frame: 12 months
The composite psoriatic disease activity index (CPDAI) assesses disease activity under five domains using well established and validated instruments of PsA disease documentation as proposed by GRAPPA. The domains and the respective instrument are as follows: joint disease (SJC/TJC, HAQ), skin involvement (PASI, DLQI), enthesitis (LEI, HAQ), dactylitis (dactylitis digit count, HAQ) and spinal involvement (BASDAI and ASQoL). Using the instruments and ranges of values, disease activity under each domain is graded as none (0) -mild (1) -moderate (2) and severe (3) giving a range attainable CPDAI scores of between 0 and 15. The CPDAI correlates well with patient and physician global disease activity assessments and is an effective tool that clearly distinguishes those who require a treatment change from those who do not.
12 months
Number of swollen and tender joints
Time Frame: 12 months
An assessment of 66 joints for swelling and 68 joints for tenderness will be made (including the DIP joints of the hands and excluding hips for swelling).
12 months
Number of tender entheseal points: SPARCC (Spondyloarthritis Consortium of Canada)
Time Frame: 12 months
The SPARCC enthesitis score is based on the counting of the presence or absence of tenderness on 16 entheseal sites (eight sites on each body side, respectively): lateral epicondyle, medial epicondyle, supraspinatus insertion into greater tuberosity of humerus, greater trochanter, quadriceps insertion into superior borders of patella, patellar ligament insertion into inferior pole of patella or tibial tubercle, Achilles tendon insertion into calcaneum, and plantar fascia insertion into calcaneum. Tenderness on examination is recorded as either present (1) or absent (0) for each of the 16 sites, summarized in an overall score ranging from 0 to 16. A higher count represents a greater enthesitis burden
12 months
Number of tender entheseal Points: LEI (Leeds Enthesitis Index)
Time Frame: 12 months
The LEI includes 3 entheseal sites on each body side, respectively: lateral epicondyles, medial condyles of the femur, and Achilles tendons. Tenderness on examination is recorded as either present (1) or absent (0) for each of the 6 sites, for in an overall score ranging from 0 to 6. A higher count represents a greater enthesitis burden
12 months
Number of tender entheseal Points: MASES (Maastricht Ankylosing Spondylitis Enthesitis Score)
Time Frame: 12 months
The MASES includes 6 entheseal sites on each body side (first costochondral joints, seventh costochondral joints, posterior superior iliac spines, anterior superior iliac spines, iliac crests, proximal insertion of Achilles tendons) and in addition the fifth lumbar spinous process. Tenderness on examination is recorded as either present (1) or absent (0) for each of the 13 sites, for an overall score ranging from 0 to 13. A higher count represents a greater enthesitis burden
12 months
Dactylitis counts
Time Frame: 12 months
The presence of dactylitis will be assessed by counting the fingers/toes with dactylitis.
12 months
Activity of psoriasis: PASI (Psoriasis Area and Severity Index)
Time Frame: 12 months
PASI combines the assessment of the severity of lesions and the area affected into a single score ranging from 0 (no disease) to 72 (maximal disease).
12 months
Activity of psoriasis: BSA (body surface area)
Time Frame: 12 months
For the BSA assessment of psoriatic skin involvement the size of the subject's hand is used as a scale to estimate the size of the skin surface covered by psoriasis. The subject's palm covers roughly 1% of body's surface area. An involved area of <3% of the skin is considered as mild, of 3 10% as moderate, and >10% as severe psoriasis
12 months
Activity of axial Involvement: BASDAI (Disease Activity of Ankylosing Spondylitis)
Time Frame: 12 months

The BASDAI consists of a one through 10 scale (one being no problem and 10 being the worst problem) which is used to answer 6 questions pertaining to the 5 major symptoms of AS: Fatigue, Spinal pain, Joint pain / swelling, areas of localized tenderness (also called enthesitis, or inflammation of tendons and ligaments), morning stiffness duration, morning stiffness severity.

To give each symptom equal weighting, the mean (average) of the two scores relating to morning stiffness is taken. The resulting 0 to 50 score is divided by 5 to give a final 0 - 10 BASDAI score. Scores of 4 or greater suggest suboptimal control of disease, and patients with scores of 4 or greater are usually good candidates for either a change in their medical therapy or for enrollment in clinical trials evaluating new drug therapies directed at Ankylosing Spondylitis

12 months
Quality of life and health/disability: PsAID-12 (Psoriatic Arthritis Impact of Disease)
Time Frame: 12 months
The PsAID-12 is a score based on a subject's self-assessment questionnaire and used to measure the impact of psoriatic arthritis on a person's life. The questionnaire comprises 12 numeric rating scale questions covering the following topics: pain, fatigue, skin problems, work/leisure activities, functional capacity, discomfort, sleep disturbance, coping with PsA, anxiety and fear and uncertainty, embarrassment and/or shame, social participation, depression. Each question receives a score from 0 to 10. For evaluation these are weighted by factors and then summarized. The range of the final PsAID-score will be 0-10 where higher figures indicate worse status.
12 months
Quality of life and health/disability: HAQ-DI (Stanford Health Assessment Questionnaire Disability Index)
Time Frame: 12 months
The Stanford Health Assessment Questionnaire is based on a subject's self-assessment questionnaire for persons diagnosed with PsA. The HAQ-DI assesses a patient's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The stem of each item asks for the past week "Are you able to …" perform a particular task. The patient's responses are made on a scale from zero (no disability) to three (completely disabled). Each category contains at least two specific component questions.
12 months
Quality of life and health/disability: DLQI (Dermatology Life Quality Index)
Time Frame: 12 months
The DLQI is a score based on a subject's self-assessment questionnaire and used to measure the impact of the skin disease (psoriasis) on the quality of life of an affected person. The questionnaire contains 10 questions covering the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment. Each question refers to the impact of the skin disease on the patient's life over the previous week. Each question receives a score from 0 to 3. These are summarized to a final score with a possible range from 0 (meaning no impact on quality of life) to 30 (meaning maximum impact on quality of life).
12 months
Quality of life and health/disability: ASQoL (Ankylosing Spondylitis Quality of Life)
Time Frame: 12 months
The ASQoL is a scale based on a subject's self-assessment questionnaire to measure the impact of ankylosing spondylitis (AS) on the quality of life of a diseased person with emphasis on the ability of the person to fulfill his or her needs. It consists of 18 items requesting a yes or no response to questions related to the impact of pain on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. The score range is 0-18. High scores indicate worse quality of life.
12 months
Quality of life and health/Disability: SF-36 (Short Form Health)
Time Frame: 12 months
SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting and are now widely utilized for routine monitoring and assessment of care outcomes in adult patients. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. The eight sections are: vitality, physical functioning, bodily pains, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
12 months
Pain (VAS)
Time Frame: 12 months
The subject will be asked to place a vertical line on a 100-mm scale on which the left-hand boundary represents "no pain," and the right-hand boundary represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary will be recorded
12 months
Proportion of patients with loss of MDA within 12 months after baseline
Time Frame: 12 months
12 months
Proportion of patients with loss of MDA within 24 months after baseline
Time Frame: 24 months
24 months
Time to loss of MDA
Time Frame: 12 months
12 months
Time needed to restore MDA after readjustment of the DMARD therapy in subjects who lost MDA within the intervention period
Time Frame: 12 months
Time [days/weeks/month] to restore after lost MDA
12 months
Biomarker levels
Time Frame: 24 months
Serum cytokines, and molecular characterization of peripheral blood cells (e.g. IL-8 (CXCL8), Calprotectin (S100A9/S100A9). IL-22, lipocalin-2 (NGAL), beta defensin 2 [11], ILC, PBMC)
24 months
Intervention-related events within the observation period of 24 months after baseline
Time Frame: 24 months
Observed symptoms (AE) related to reduction (intervention) such as symptoms suspicious of worsening disease activity (flare)
24 months
AE (Adverse Event)
Time Frame: 12 months
Adverse Event
12 months
AR (Adverse Reaction)
Time Frame: 12 months
Adverse Reaction
12 months
SAE (Serious Adverse Event)
Time Frame: 12 months
Serious Adverse Event
12 months
SAR (Serious Adverse Reaction)
Time Frame: 12 months
Serious Adverse Reaction
12 months
SUSAR (Suspected Unexpected Serious Adverse Reaction)
Time Frame: 12 months
Suspected Unexpected Serious Adverse Reaction
12 months

Collaborators and Investigators

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

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)

October 19, 2020

Primary Completion (Anticipated)

October 19, 2024

Study Completion (Anticipated)

October 19, 2025

Study Registration Dates

First Submitted

September 18, 2020

First Submitted That Met QC Criteria

October 29, 2020

First Posted (Actual)

October 30, 2020

Study Record Updates

Last Update Posted (Actual)

November 14, 2022

Last Update Submitted That Met QC Criteria

November 10, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Other Study ID Numbers

  • UKER-ATTRACTOR -01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

After all data of the trial were published by the study group, the data might be provided to interested scientists on request (e.g. for meta-analyses, health related registers or other scientific questions) in an anonymized way, if the members of the study group agree.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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