E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 |
The primary objective of this study is to assess the change in immunohistochemical markers of synovial inflammation from baseline to 6 months, in patients with active PsA (CASPAR criteria) of > 3 months duration.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to assess:
1.MRI changes over time in PsA patients on Abatacept.
2.Articular and skin clinical outcomes over time in patients with PsA on Abatacept.
3.Skin immunohistologic change, in particular change in T-reg expression comparison between baseline, 1 and 6 months in patients on Abatacept.
To assess the safety and tolerability of Abatacept in this study population, evaluated by number of adverse events related to drug therapy.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must give written informed consent,
given prior to any study-related procedure not part of the patient’s normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to his or her future medical care.
Patients between the ages 18 and 80 years, with a joint disease onset after 16 years old
Patients with active PsA (CASPAR criteria) of > 3 months duration defined by the following criteria: Active arthritis with >3 swollen joints and >3 tender joints considered capable of responding to drug therapy. Should present a clinical synovitis of a knee and have accepted to undergo synovial biopsies ? At least one of the inflamed joints should be a knee joint.§ An evaluable psoriatic skin lesion, diagnosed by a consultant rheumatologist or a dermatologist is not a pre-requisite but where possible such patients will be recruited . |
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E.4 | Principal exclusion criteria |
·WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to14 weeks after the last dose of tre·atment Female patients who are pregnant or breast-feeding. ·Subjects who meet diagnostic criteria for any other rheumatic disease
Subjects who are impaired, incapacitated, or incapable of completing study related assessments (including prisoners and patients detained for treatment of psychiatric illness)· Evidence of skin conditions other than psoriasis .· History of cancer in the preceding 5 years (except adequately treated basal cell carcinoma of the skin and carcinoma in situ of the skin).· Subjects with current clinical or laboratory evidence of active tuberculosis .· Latent TB which was not successfully treated.·Active severe infection · Have history of drug (including narcotics) abuse, or current active problems with drug or alcohol abuse· Subjects who have received a previous systemic treatment with biologic DMARDs, including cytokines/anti-cytokines |
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E.5 End points |
E.5.1 | Primary end point(s) |
Response to treatment will be measured by the change in immunohistochemical markers of synovial inflammation from baseline to 6 months in patients with active PsA (CASPAR criteria) of > 3 months duration.
Using a standard mini-arthroscopic procedure, synovial tissue will be obtained from an inflamed knee joint at 0, 1 and 6 months. Tissue will be embedded in OCT for standard immunohistochemical staining to include cell surface markers (CD3, CD4, CD8, CD68), intracellular T Reg marker FoxP3 and markers of vascularity (Factor VIII). Additional stains for T cell activation markers (CD28) can also added. Staining will be quantified by digital image analysis as outlined below and compared at each time point. All of the synovial immunohistologic analysis will be performed at the end of the study
Digital image analysis
Eighteen high power images will be taken per slide for each of the cell specific markers stained. In the case of CD68, the intimal lining layer will be highlighted manually per image, such that staining can be quantified in 2 areas - the intimal lining (LL) and synovial sublining (SL) layers. Analysis will be performed using the Qwin analysis system (Leica, Cambridge, UK). Results will be expressed as the number of positively stained cells/mm2 of tissue for CD3, CD4, CD8, CD68 and Fox P3 and by integrated optical density (IOD) /mm2 for FVIII.
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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 | No |
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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | 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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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
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 |