| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
| A type of arthritis that develops in some people with the skin condition psoriasis causing affected joints to become swollen and painful. |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10037160 |
| E.1.2 | Term | Psoriatic arthritis |
| E.1.2 | System Organ Class | 100000004859 |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare the initial effectiveness of early combination DMARD therapy (arm 2) and early use of TNF inhibitors (arm 3) with standard step up care (received in the TWiCs cohort; arm 1). |
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| E.2.2 | Secondary objectives of the trial |
To assess the speed of response to therapy in the treatment arms.
To assess later effectiveness of the treatment arms.
To establish effectiveness of the treatment arms on the new domains of the PsA core set (participation, fatigue and emotional wellbeing).
To assess the cost-effectiveness of the treatment arms.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 REC Ref 17/SC/0556) and to be approached for alternate interventional therapies.
• Poor prognostic factors at baseline. Either
o Polyarticular disease with ≥5 active joints at baseline assessment OR
o 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:
o Haemoglobin count > 8.5 g/dL
o White blood count (WBC) > 3.5 x 109/L
o Absolute neutrophil count (ANC) > 1.5 x 109/L
o Platelet count > 100 x 109/L
o AST or 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 GP and consultant, if appropriate, to be notified of participation in the trial.
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| E.4 | Principal exclusion criteria |
• Previous treatment for articular disease with disease modifying drugs (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 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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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary outcome is the response according to PASDAS. This will be reported as the proportion achieving a PASDAS good response (reduction from baseline of ≥1.6 and final score of ≤3.2) in each of the three treatment groups (standard step up therapy in the cohort, early combination DMARD or early TNF inhibitor therapy) at week 24. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Clinical assessment, patient questionnaires and blood tests all performed at weeks 0 and 24 |
|
| E.5.2 | Secondary end point(s) |
Secondary outcome measures:
- Time to achievement of minimal disease activity (MDA)
- The proportion of patients achieving a PASDAS good response at week 48; proportion achieving PASDAS moderate response at week 24 and 48
- Change in PsA impact of disease (PSAID) score from baseline to follow up
Proportion achieving PSAID patient acceptable symptom state (≤4) at follow up
Change in work productivity (absenteeism, presenteeism and productivity loss) as measured by WPAI at follow up.
- Cost per QALY in each treatment arm to calculate ICER
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
For the above respectively:
- Assessed every 12 weeks
- Clinical assessment, patient questionnaires and blood tests all performed at weeks 0, 24 and 48.
- Patient questionnaires at weeks 0, 24, and 48 weeks
- Healthcare resource use data and health related quality of life throughout the study |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Standard care methotrexate with step up if needed vs. early combination therapy vs. early TNF inhib |
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| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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