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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03739853
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 4
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Oxford
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries United Kingdom
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Psoriatic Arthritis
Additional Details

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.

Arms & Interventions

Arms

Active Comparator: Standard care

Control 'step-up' therapy in the cohort (MONITOR-PsA study). Therapy for the cohort is defined by standard NHS practice following international recommendations and National requirements for the prescription of biologic therapy[19-22]. 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. 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. If the requisite disease activity is not met or if there are contraindications to biologics, alternative DMARD combinations will be used.

Experimental: Combination csDMARD

Arm 2 - Combination DMARD arm. All participants will be prescribed methotrexate with an additional DMARD (either sulfasalazine or leflunomide) at baseline. Response will be assessed after 12 weeks of therapy using the Minimal Disease Activity (MDA) criteria. Participants who achieve the MDA criteria by week 12 on this combination therapy will continue . 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

Experimental: Early TNF inhibition

Early biologic arm. All participants will be prescribed methotrexate (given weekly) with a TNF inhibitor (adalimumab given every two weeks) at baseline. Treatment with TNF inhibitor will be continued until week 24 at which time the TNF inhibitor will be tapered to 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

Interventions

Drug: - Methotrexate

Used in all three arms of study

Drug: - Sulfasalazine

Used in arm 2 of study

Drug: - Leflunomide

Used in arm 2 of study

Drug: - Adalimumab

Used in arm 3 of the study only

Contact a Trial Team

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International Sites

Oxford University Hospitals NHS Trust, Oxford, Oxfordshire, United Kingdom

Status

Recruiting

Address

Oxford University Hospitals NHS Trust

Oxford, Oxfordshire, OX3 7LD

Site Contact

Laura C Coates, MBChB

[email protected]

01865737838

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