E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003268 |
E.1.2 | Term | Arthritis rheumatoid |
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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 evaluate the safety and efficacy of anti-IgE therapy with respect to: Clinical (DAS), laboratory parameters and adverse events. - To evaluate whether disease activity correlates with immunological parameters, including immunopathology and IgE-ACPA-autoantibodies.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with refractory active rheumatoid arthritis (RA). Refractory disease is defined as persistent or relapsed disease activity despite conventional treatment, i.e. combination of disease modifying antirheumatic drugs including maximal tolerable doses of methotrexate. Active disease is defined as a DAS44 (Disease Activity Score of 44 joints) score of more than 3.6 2. Presence of IgE-ACPA 3. Age above 18 years 4. WHO performance status 0, 1 or 2 5. Informed consent according to rules and regulations of Leiden University Medical Center.
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E.4 | Principal exclusion criteria |
1. History of allergic or anaphylactic reaction to any therapeutic agent or known hypersensitivity to any component of anti-IgE monoclonal antibodies or to murine proteins. 2. No previous therapy with corticosteroids or a biological agent during the last 3 months. 3 No previous therapy with rituximab, leflunomide 4. Life expectation of less than 6 months 5. History of severe CNS disturbances and psychiatric problems 6. Severe uncontrolled infections including parasitosis 7. Irreversible major organ dysfunction, defined by any of the following criteria: - creatinine clearance < 40 ml/min. - left ventricular ejection fraction < 40%; - pericardial effusion with haemodynamic consequences. - resting arterial oxygen tension (PaO2) < 8 kPa (<60 mmHg) and / or resting arterial carbon dioxide tension (PaCO2) > 6.7 kPa (>50 mmHg). - sustained 3-fold increase in serum transaminase or bilirubin. 8. HIV positivity 9. Positive pregnancy test or unwillingness to use adequate contraception for the duration of the study 10. History of cancer, including solid tumors, hematological malignancies and carcinoma in situ (except for basal cell and squamous cell carcinoma of the skin that have been treated and cured).
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Clinical parameters for disease activity are measured by the DAS44 (Disease Activity Score on 44 joints) assessment. Responses are classified as follows: -Complete response is defined as a DAS44 improvement of > 1.2 and DAS<2.4 -Moderate response is defined as DAS44 improvement of 1.2 and DAS >2.4: OR DAS 44 improvement of >0.6 en <=1.2 and DAS <=3.7: -Non-response is defined as DAS44 improvement of >0.6 en <=1.2 improvement and DAS >3.7 OR improvement of <=0.6 2. Immunological parameters in peripheral blood and synovium after treatment with anti-IgE antibodies (omalizumab) are: - proportion of peripheral blood basophils, mast cells in synovium - functional presence of IgE-ACPA, - IgE , FcERI expression on basophils, mast cells, B cells and DC - synovial infiltration of B cells, plasmacells, mast cells and (IgE-)ACPA presence in synovial fluid 3. Safety and toxicity parameters are evaluated according to WHO Common Toxicity Criteria
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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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | 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.8.5 | 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 | 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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end of trial is the last visit |
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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 | 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 |