Treatment strategies aiming at minimal disease activity in psoriatic arthritis

ISRCTN	ISRCTN76054545
DOI	https://doi.org/10.1186/ISRCTN76054545
EudraCT/CTIS number	2018-004724-11
Secondary identifying numbers	versie 3.0 – 11-06-2019

Submission date: 04/12/2019
Registration date: 05/12/2019
Last edited: 09/07/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Skin and Connective Tissue Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Psoriatic arthritis is a type of arthritis that develops in some people with the skin condition psoriasis. It typically causes affected joints to become inflamed (swollen), stiff and painful. Like psoriasis, psoriatic arthritis is a long-term condition that can get progressively worse. In severe cases, there's a risk of the joints becoming permanently damaged or deformed, which may require surgical treatment. However, with an early diagnosis and appropriate treatment, it's possible to slow down the progression of the condition and minimise or prevent permanent damage to the joints.

The objective is to compare the effectiveness of the administration of secukinumab to standard care in newly diagnosed Psoriatic Arthritis (PsA) patients.

Who can participate?
Patients aged 18 – 80 years who have recently been diagnosed with psoriatic arthritis with at least 2 joints with arthritis and have received no treatment with anti-rheumatic drugs.

What does the study involve?
Participants will be randomly assigned to receive standard care or Secukinumab for a 3-month period

What are the possible benefits and risks of participating?
The benefits are that patients are closely monitored fot therapy effect and they can receive secukinumab as first line treatment. The risk of early secukinumab could be a chance of more side effect mainly infectious. People do not have to come to the hospital more frequently, but there visits might be longer and they have to fill in extra questionaires.

Where is the study run from?
Erasmus MC, the Netherlands

When is the study starting and how long is it expected to run for?
December 2019 to December 2024

Who is funding the study?
Novartis, Switzerland

Who is the main contact?
Dr Marijn Vis
marijn.vis@erasmusmc.nl

Study website

Contact information

Dr Marijn Vis
Scientific

Dr Molewaterplein 40
Rotterdam
3015GD
Netherlands

ORCID ID	0000-0002-4402-4165
Phone	+31614928440
Email	marijn.vis@erasmusmc.nl

Study information

Study design	Randomized controlled parallel group open label multi-center study
Primary study design	Interventional
Secondary study design	Randomised parallel trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use contact details to request a participant information sheet.
Scientific title	Clinical effectiveness of two treat to target strategies, mimicking standard care compared to early secukinumab for the treatment of moderate to severe psoriatic arthritis: a parallel group randomised controlled trial
Study acronym	STAMP
Study objectives	Treatments covering all features of PsA by early aggressive therapeutic intervention, using secukinumab as an initial treatment strategy will improve Treat to Target (T2T) in PsA
Ethics approval(s)	Approved 07/08/2019, METC Erasmus MC (Postbus 2040, 3000CA, Rotterdam, the Netherlands; +31 107033625; metc@erasmusmc.nl), ref: NL68512.078.18
Health condition(s) or problem(s) studied	Psoriatic arthritis
Intervention	Participants will be randomised to two arms using 1:1 block randomisation at each center (block size 6 patients) Arm 1: Standard care. The standard care is based on data from the DEPAR cohort and interviews with Dutch rheumatologists. Arm 2: Secukinumab. Patients will be started on Secukinumab 300mg subcutaneous. Therapy in each arm will be escalated using a 3 monthly scheme in patients not achieving the treatment target Minimal Disease Activity (MDA)3. Participants in this study will attend for study visits at baseline and months 3, 6, 9 and 12. After 6 weeks patients will be asked to fill out 5 questionnaires. At the 3-monthly visits, participants will be assessed clinically for disease activity and will be asked to complete patient reported outcomes via questionnaires. Visits in between these will be performed based on clinical need when adjustment to therapy is required. Arm 1: Standard care. Therapy for the cohort is defined by the usual treatment strategy applied by rheumatologists for the treatment of oligo- and polyarticular PsA. The initial therapy (step 1) in this arm is MTX mono-therapy (starting 15mg/week rising escalated to 25mg/week in 6 weeks). In addition, all patients will be administered triamcinolone 80mg intramuscular (IM). In cases of non-response, sulfasalazine twice daily 1000mg will be added to the MTX (step 2). In case of failure of these two DMARDs, treatment will be escalated by adding a biological DMARD. In this study is opted for a TNF blocker (step 3). When the combination of conventional DMARD and a first TNF blocker fails, the TNF blocker will be switched to a second TNF blocker (step 4). The choice of which TNF blocker to use is at the discretion of the treating rheumatologist. The dosing of TNF blockers will be the standard dose for PsA according to current guidelines in line with National reimbursement guidelines. Arm 2: Secukinumab. All participants will be prescribed secukinumab 300 mg every 4 weeks, with a loading scheme of the first four 300 mg injections weekly, in combination with MTX 15mg/week . In addition, all patients will be administered triamcinolone 80 mg intramuscular (IM) (step 1). Secukinumab is not registered for the first line treatment of PsA patients and is not in accordance with national reimbursement guidelines. In case the first step fails (secukinumab 300mg + MTX 15mg/week) treatment will be switched to a TNF blocker (step 2) and to a second TNF blocker if the first TNF blocker fails (step 3). The choice of which TNF blocker to use is at the discretion of the treating rheumatologist. The dosing of TNF blockers will be the standard dose for PsA according to current guidelines in line with national reimbursement guidelines. When a second TNF blocker fails, this drug will be switched to apremilast 30mg twice daily (step 4). Apremilast therapy is in line with national reimbursement guidelines.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase IV
Drug / device / biological / vaccine name(s)	Secukinumab, Methotrexate, Sulfasalazine, TNF-blocker, Apremilast
Primary outcome measure	Disease activity measured using the ACR50 at 6 months
Secondary outcome measures	1. Disease activity measured using the ACR 20 and 70 at 6 months 2. Disease activity measured using the ACR 20, 50, 70 at 12 months 3. Disease activity measured using MDA and Very low disease activity (VLDA) at 6 and 12 months 4. Disease activity. measured using Disease Activity in Psoriatic Arthritis (DAPSA) score at 6 and 12 months 5. Disease activity. measured using Psoriatic Arthritis Disease Activity Score (PASDAS) score at 6 and 12 months 6. General health measured using the Short-form 36 at 12 months 7. Impact of disease measured using Psoriatic Arthritis Impact of Disease (PSAID) at 12 months 8. Fatigue measured using Bristol Rheumatoid Arthritis Fatigue (BRAF) at 12 months
Overall study start date	07/06/2019
Completion date	01/12/2024

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	120
Key inclusion criteria	1. Newly diagnosed by the rheumatologist and fulfilling the Classification criteria for Psoriatic Arthritis (CASPAR) 2. Present with oligo-arthritis (2 to 5 involved joints) or with poly-arthritis (5 or more joints) 3. Patients must be able to understand and communicate with the Investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed 4. Male or female patients between 18 and 80 years of age 5. In the Investigator’s opinion, the patient is able and willing to comply to all trial requirements 6. Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the trial and for 3 months thereafter as in standard practice
Key exclusion criteria	1. Evidence of ongoing infectious or malignant process obtained within 3 months prior to screening and evaluated by a qualified health care professional. 2. Current or previous treatment of arthritis with DMARDs (including MTX, leflunomide or sulfasalazine) or biologics (including TNF, IL12/23 or IL17 inhibitor therapies) 3. Use of any investigational drug and/or devices within 4 weeks prior to randomization or a period of five half-lives of the investigational drug, whichever is longer in duration. 4. Pregnant or nursing (lactating) women, in which pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. 5. Underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions which in the opinion of the Investigator immunocompromises the patient and/or places the patient at unacceptable risk for participation in an immunomodulatory therapy. 6. Significant medical problems or diseases, including but not limited to the following: uncontrolled hypertension (≥ 160/95 mmHg), congestive heart failure (New York Heart Association status of class III or IV) and uncontrolled diabetes. 7. History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests (LFT) of e.g. aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT), alkaline phosphatase, and/or serum bilirubin. The Investigator should be guided by the following criteria: Any single parameter may not exceed 2 x upper limit of normal (ULN). A single parameter elevated up to and including 2 x ULN should be re-checked once more as soon as possible, and in all cases, at least prior to enrollment/randomization, to rule out laboratory error. 8. History of renal trauma, glomerulonephritis, or subjects with one kidney only, or a glomerular filtration rate (GFR) < 30 ml/min. 9. Active systemic infections during the last two weeks (exception: common cold) prior to randomization. 10. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection as defined by either a positive Purified Protein Derivative (PPD) skin test or a positive QuantiFERON TB-Gold test untreated or insufficiently treated according to the national guideline. 11. Known infection with human immunodeficiency virus, hepatitis B or hepatitis C at screening or randomization. 12. History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed). 13. Current severe progressive or uncontrolled disease, which in the judgment of the clinical Investigator renders the patient unsuitable for the trial. 14. Inability or unwillingness to undergo repeated venipuncture (e.g. because of poor tolerability or lack of access to veins). 15. Any medical or psychiatric condition which, in the Investigator’s opinion, would preclude the participant from adhering to the protocol or completing the study per protocol. 16. History or evidence of ongoing alcohol or drug abuse, within the last 6 months before randomization
Date of first enrolment	08/12/2019
Date of final enrolment	08/12/2021

Locations

Countries of recruitment

Netherlands

Study participating centres

Erasmus MC

dr Molewaterplein 40
Rotterdam
3015-GD
Netherlands

Maasstadziekenhuis

Maasstadweg 21
Rotterdam
3079DZ
Netherlands

Vlietland Ziekenhuis

Vlietlandplein 2
Schi
3118JH
Netherlands

Albert Schweitzer Ziekenhuis

Albert Schweitzerplaats 25
Dordrecht
3318AT
Netherlands

Admiraal de Ruyter Ziekenhuis

's-Gravenpolderseweg 114
Goes
4462RA
Netherlands

Amphia Ziekenhuis

Molengracht 21
Breda
4818CK
Netherlands

RZWN Roosendaal

Streuvelslaan 18
Roosendaal
4707CH
Netherlands

Ijsselland Ziekenhuis

Prins Constantijnweg 2
Capelle
2906ZC
Netherlands

HagaZiekenhuis

Els Borst-Eilersplein 275
Den Haag
2545AA
Netherlands

Groene Hart Ziekenhuis

Bleulandweg 10
Gouda
2803HH
Netherlands

RZWN Goes

Van Hertumweg 17
Goes
4462EV
Netherlands

Reinier de Graaf Ziekenhuis

Reinier de Graafweg 5
Delft
2625AD
Netherlands

Sponsor information

Erasmus MC
Hospital/treatment centre

Dr Molewaterplein 40
Rotterdam
3015GD
Netherlands

Phone	+31 107040704
Email	J.hazes@erasmusmc.nl
"ROR"	https://ror.org/018906e22

Funders

Funder type

Industry

Novartis
Government organisation / For-profit companies (industry)

Alternative name(s): Novartis AG, Novartis International AG
Location: Switzerland

Results and Publications

Intention to publish date	01/12/2025
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Publish a primary paper with the primary results in a peer reviewed journal within 6 months after completion. Dissemination will also be through conferences and national guidelines.
IPD sharing plan	The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Data will only be available for reviewers and journals who wish to verify results. Data will also be available to researchers wishing to collaborate after the proper paper work has been done.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol file	version v3.0	11/06/2019	10/01/2020	No	No

Additional files

ISRCTN76054545_PROTOCOL_v3.0_11Jun19.pdf: Uploaded 10/01/2020

Editorial Notes

09/07/2024: The overall end date was changed from 07/06/2022 to 01/12/2024.
10/01/2020: Uploaded protocol Version 3.0, 11 June 2019 (not peer reviewed).
05/12/2019: Trial’s existence confirmed by METC Erasmus MC.