E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Inflammatory knee mono-arthritis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062164 |
E.1.2 | Term | Seronegative arthritis |
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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 determine clinical and ultrasound (power doppler) predictors of response to intra-articular Infliximab therapy in patients with persistent inflammatory mono-arthritis of the knee in a prospective observational cohort. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Sero-negative inflammatory knee mono-arthritis, including psoriatic, enteropathic, reactive and undifferentiated seronegative spondyloarthropathy (SpA). 2. Age range 18 – 80 3. Active disease despite concomitant treatment with one of the following DMARDs as monotherapy, with no dose change for the preceding 8 weeks (2 months): Sulphasalazine (2g – 3g daily up to maximum tolerated dose) Methotrexate (7.5 – 20 mg weekly up to maximum tolerated dose) Leflunomide (10 – 20mg daily up to maximum tolerated dose) Ciclosporin (2.5 mg/kg body weight) Where no DMARD has been co-prescribed Sulphasalazine will be started at 500 mg b.d. for a week and then increased to 1g b.d. for a further 8 weeks before entry criteria are re-assessed. 4. Active disease defined as i) composite knee score 4 or more (21) ii) VAS score > 5 for pain on walking and on ascending/descending stairs iii) evidence of synovial vascularity on PDS (score 2 or 3) in views obtained from either the suprapatellar fossa, lateral or medial parapatellar spaces (18).
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E.4 | Principal exclusion criteria |
1. Inability to tolerate DMARD monotherapy 2. Systemic corticosteroid therapy 3. Systemic or intra-articular anti-TNF alpha or other biologic therapy within the preceding 3 months. 4. Knee aspiration or intra-articular corticosteroid, yttrium or osmic acid injection within the preceding 3 months 5. Arthroscopic lavage or other operative procedure within the preceding 3 months 6. Established contra-indications to anti-TNF alpha therapies (e.g. chronic infectious diseases) or previous intolerance to Infliximab
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary measure of treatment efficacy will be determined by a fall in PDS score to 0 or 1 in all 3 regions of the knee (suprapatellar fossa, lateral and medial parapatellar spaces) within 12 weeks of the injection of Infliximab (23). Secondary measures of efficacy will be an improvement in clinical measures, i.e. composite knee score of 2 or less and a reduction in VAS scores to 2 or less within 12 weeks. The proportion of patients achieving efficacy according to PDS and each clinical measure will be recorded at weeks 2, 4, 8 and 12. |
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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 | Yes |
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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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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For each patient the trial will end either after 'treatment failure' (failure to induce a reduction in PDS score to 0 or 1 in all 3 regions of the knee by 12 weeks) or after relapse of disease activity following the second Infliximab injection.
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |