Condition category
Skin and Connective Tissue Diseases
Date applied
04/12/2019
Date assigned
05/12/2019
Last edited
10/01/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

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 June 2022

Who is funding the study?
Novartis, Switzerland

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

Trial website

https://www.ciceroreumatologie.nl/

Contact information

Type

Scientific

Primary contact

Dr Marijn Vis

ORCID ID

http://orcid.org/0000-0002-4402-4165

Contact details

Dr Molewaterplein 40
Rotterdam
3015GD
Netherlands
+31614928440
marijn.vis@erasmusmc.nl

Additional identifiers

EudraCT number

2018-004724-11

ClinicalTrials.gov number

Nil known

Protocol/serial number

versie 3.0 – 11-06-2019

Study information

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

Acronym

STAMP

Study hypothesis

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

Approved 07/08/2019, METC Erasmus MC (Postbus 2040, 3000CA, Rotterdam, the Netherlands; +31 107033625; metc@erasmusmc.nl), ref: NL68512.078.18

Study design

Randomized controlled parallel group open label multi-center study

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

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

Phase

Phase IV

Drug names

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 trial start date

07/06/2019

Overall trial end date

07/06/2022

Reason abandoned (if study stopped)

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

120

Participant 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

Recruitment start date

08/12/2019

Recruitment end date

08/12/2021

Locations

Countries of recruitment

Netherlands

Trial participating centre

Erasmus MC
dr Molewaterplein 40
Rotterdam
3015-GD
Netherlands

Trial participating centre

Maasstadziekenhuis
Maasstadweg 21
Rotterdam
3079DZ
Netherlands

Trial participating centre

Vlietland Ziekenhuis
Vlietlandplein 2
Schi
3118JH
Netherlands

Trial participating centre

Albert Schweitzer Ziekenhuis
Albert Schweitzerplaats 25
Dordrecht
3318AT
Netherlands

Trial participating centre

Admiraal de Ruyter Ziekenhuis
's-Gravenpolderseweg 114,
Goes
4462RA
Netherlands

Trial participating centre

Amphia Ziekenhuis
Molengracht 21
Breda
4818CK
Netherlands

Trial participating centre

RZWN Roosendaal
Streuvelslaan 18
Roosendaal
4707CH
Netherlands

Trial participating centre

Ijsselland Ziekenhuis
Prins Constantijnweg 2
Capelle
2906ZC
Netherlands

Trial participating centre

HagaZiekenhuis
Els Borst-Eilersplein 275
Den Haag
2545AA
Netherlands

Trial participating centre

Groene Hart Ziekenhuis
Bleulandweg 10
Gouda
2803HH
Netherlands

Trial participating centre

RZWN Goes
Van Hertumweg 17
Goes
4462EV
Netherlands

Trial participating centre

Reinier de Graaf Ziekenhuis
Reinier de Graafweg 5
Delft
2625AD
Netherlands

Sponsor information

Organisation

Erasmus MC

Sponsor details

Dr Molewaterplein 40
Rotterdam
3015GD
Netherlands
+31 107040704
J.hazes@erasmusmc.nl

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

Novartis

Alternative name(s)

Novartis AG, Novartis International AG

Funding Body Type

private sector organisation

Funding Body Subtype

For-profit companies (industry)

Location

Switzerland

Results and Publications

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 statement:
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.

Intention to publish date

01/12/2022

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

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.