Severe Psoriatic Arthritis - Early intervEntion to Control Disease: the SPEED Trial

  • STATUS
    Recruiting
  • days left to enroll
    17
  • participants needed
    315
  • sponsor
    University of Oxford
Updated on 5 May 2021
platelet count
methotrexate
adalimumab
tumor necrosis factor
arthritis
rheumatic diseases
sulfasalazine
anti-rheumatic drugs
tumour necrosis
leflunomide

Summary

SPEED is a three arm interventional trial nested within a cohort (Trials Within Cohorts or TWiCs design). This tests more aggressive early therapy in patients newly diagnosed with moderate to severe PsA. Arm 1 will receive standard step up therapy in the cohort and act as the control group. Arm 2 will receive early combination conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). Arm 3 will receive early tumour necrosis factor (TNF) inhibitor therapy.

Description

Arm 1: Control 'step-up' therapy in the cohort (MONITOR-PsA study). Therapy for the cohort is defined by standard practice in these PsA clinics following current international recommendations[11] and National requirements for the prescription of biologic therapy[19-22]. Whilst physician discretion is used, most commonly Initial therapy will be with methotrexate alone (15mg/week rising to 25mg/week as tolerated by week 8 of therapy) unless this is contraindicated. In cases of non-response or intolerance to methotrexate, participants will have an alternative DMARD (most commonly sulfasalazine or leflunomide) added or switched to at the discretion of the rheumatologist. In cases of failure of two DMARDs, treatment can be escalated to biologic therapy as per National Institute for Health and Clinical Excellence (NICE) recommendations[19-22] usually with a TNF inhibitor as first line. If the requisite disease activity is not met or if there are contraindications to biologics, alternative DMARD combinations will be used. Further details are available in the PsA clinic treatment protocol which is Appendix D in the MONITOR-PsA protocol.

ARM 2: Combination DMARD arm. All participants will be prescribed methotrexate with an additional DMARD (either sulfasalazine or leflunomide) at baseline, staggering the start of these additional therapies by one week to allow more accurate attribution of adverse events. Either sulfasalazine or leflumonide will be used in combination depending on physician preference (taking into account disease presentation, arthritis, enthesitis, skin disease, risk of hypertension and liver disease).Response will be assessed after 12 weeks of therapy using the Minimal Disease Activity (MDA) criteria. These assess 7 different outcomes and patients should meet at least 5 of the 7 items to be classified as being in MDA. Participants who achieve the MDA criteria by week 12 on this combination therapy will continue on this therapy. Participants who show a significant response by in week 12 (a reduction in tender and swollen joint counts of at least 20%) but do not yet meet the MDA criteria should continue on this therapy for an additional 12 weeks before review. Participants failing to show significant response (reduction in joint counts by less than 20%) by week 12 on this combination therapy or those failing to meet MDA criteria by week 24 will be eligible for rescue therapy following the standard PsA clinic treatment protocol (as per arm 1 above and as detailed in the PsA clinic treatment protocol which is found in appendix D of the MONITOR-PsA protocol). Participants may be eligible at this time point for biologic therapy most commonly using TNF inhibitors under NICE guidelines. These state that patients should have failed adequate trials of at least 2 standard DMARDs and that they should have active disease defined as at least 3 tender and 3 swollen joints. If they do not fulfil these NICE criteria (3 tender and 3 swollen joints) they will be prescribed alternative DMARDs.

ARM 3: Early biologic arm. All participants will be prescribed methotrexate (given weekly) with a TNF inhibitor (adalimumab given every two weeks) at baseline staggering the start of these therapies by one week to allow more accurate attribution of adverse events (TNF inhibitor from week 0, methotrexate from week 1). Treatment with TNF inhibitor will be continued until week 24 at which time the TNF inhibitor will be tapered by spacing out doses which will be received at week 28 and week 32. The TNF inhibitor will be stopped completely after week 32 and participants will continue on methotrexate. In case of flare of disease, participants will be eligible for rescue therapy following the standard PsA clinic treatment protocol (as per arm 1 above and as detailed in the PsA clinic treatment protocol which is found in appendix D of the MONITOR-PsA protocol). According to this protocol they will be started on combination DMARD therapy (sulfasalazine or leflunomide) and may subsequently be eligible for further TNF inhibitor treatment at a later point if they fulfil NICE criteria (as above).

The Investigational Medicinal Products (IMPs) used in this trial are methotrexate, sulfasalazine, leflunomide and adalimumab. All of these medications are used routinely in PsA patients in standard care.

Details
Condition Psoriasis, Psoriasis and Psoriatic Disorders, PSORIATIC ARTHRITIS, PSORIATIC ARTHRITIS, Arthritis, Arthritis and Arthritic Pain, Arthritis and Arthritic Pain (Pediatric), Arthritis and Arthritic Pain, Psoriasis and Psoriatic Disorders, Arthritis and Arthritic Pain (Pediatric)
Treatment methotrexate, Adalimumab, leflunomide, Sulfasalazine
Clinical Study IdentifierNCT03739853
SponsorUniversity of Oxford
Last Modified on5 May 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Participant is willing and able to give informed consent for participation in the trial
Male or Female, aged 18 years or above
Participants consented to the PsA inception cohort (MONITOR-PsA) and to be approached for alternate interventional therapies
Poor prognostic factors at baseline. Either
Polyarticular disease with 5 active joints at baseline assessment OR
Oligoarticular disease with <5 active joints at baseline but with one or more of the following poor prognostic factors: raised C reactive protein, radiographic damage, health assessment questionnaire>1
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 (or 2 years if received leflunomide unless treated with washout therapy) as in standard practice
Participant has clinically acceptable laboratory results within 28 days of baseline
Haemoglobin count > 8.5 g/dL
White blood count (WBC) > 3.5 x 109/L
Absolute neutrophil count (ANC) > 1.5 x 109/L
Platelet count > 100 x 109/L
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and alkaline phosphatase levels <3 x upper limit of normal
In the Investigator's opinion, is able and willing to comply with all trial requirements
Willing to allow his or her general practitioner and consultant, if appropriate, to be notified of participation in the trial

Exclusion Criteria

Previous treatment for articular disease with DMARDs including, but not limited to, methotrexate, sulfasalazine, leflunomide and ciclosporin
Female patient who is pregnant, breast-feeding or planning pregnancy during the course of the trial
Significant renal (estimated glomerular filtration rate <30ml/min) or hepatic impairment
Patients who test positive for Hepatitis B, C or HIV
Contraindication to any of the investigative drugs
Patients who currently abuse drugs or alcohol
Scheduled elective surgery or other procedures requiring general anaesthesia during the trial
Patient with life expectancy of less than 6 months
Any other significant disease or disorder which, in the opinion of the Investigator, may either put patients at risk because of participation in the trial, or may influence the result of the trial, or their ability to participate in the trial
Participation in another research trial involving an investigational product in the past 12 weeks
Additional exclusion criteria apply to patients randomised to arm 3 and
receiving adalimumab therapy
Active tuberculosis (TB), chronic viral infections, recent serious bacterial infections, those receiving live vaccinations within 3 months of the anticipated first dose of study medication, or those with chronic illnesses that would, in the opinion of the investigator, put the participant at risk
Latent TB unless they have received appropriate anti-tuberculous treatment as per local guidelines
History of cancer in the last 5 years, other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ
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