E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult Rheumatoid Arthritis (RA) |
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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 | 10039073 |
E.1.2 | Term | Rheumatoid 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 assess the mechanisms of TCZ effects on neutrophil function and survival. |
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E.2.2 | Secondary objectives of the trial |
To assure safety (adverse events, laboratory abnormalities, using risk minimization strategies for AEs of Special Interest, section 7) and benefit:risk of TCZ 8 mg/kg as monotherapy or in combination with allowed non-biologic DMARDs, according to SPC and evaluation of benefit by improvements in DAS28. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult (≥ 18 years) patients with moderate to severe active RA of ≥ 6 months duration DAS28 ≥ 3.2 at screening and baseline Patients must have discontinued biologic DMARDs prior to receiving tocilizumab (patient must have discontinued etanercept for ≥ 2 weeks, infliximab or adalimumab for ≥ 8 weeks, anakinra for ≥ 1 week, rituximab > 24 weeks [or B-cell count has returned to levels prior to treatment and patient meets requirement for active disease]) If continuing non-biologic DMARDs, the dose must be stable for 8 weeks
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E.4 | Principal exclusion criteria |
Major surgery (including joint surgery) within 8 weeks prior to screening or not recovered from prior surgery History of or current inflammatory joint disease or rheumatic autoimmune disease other than RA Active current infection or history of recurrent bacterial, viral, fungal, or mycobacterial infection Pregnant women or nursing (breast feeding) mothers |
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E.5 End points |
E.5.1 | Primary end point(s) |
Neutrophil survival and function results reported descriptively: Apoptosis: - Neutrophil morphology by light microscopy (change in proportion of cells apoptotic) utilizing a combination of staining and dynamic confocal microscopy - Change in cell surface molecules: activation marker CD16, and membrane phosphatidyl serine Neutrophil function: - by ex vivo flow cytometry measurement of surface molecule expression, including Fcγ-receptor, and - Phagocytosis markers ex vivo (respiratory burst, labeled bacteria) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | 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 | 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 | 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 | 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
|
The end of the trial is defined as the date of the last visit of the last participating patient in this study (LPLV; week 52) |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | |