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 |
Moderate to severe active rheumatoid arthritis. |
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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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 long-term safety of 8 mg/kg tocilizumab (MRA) with regard to adverse events and laboratory result abnormalities
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E.2.2 | Secondary objectives of the trial |
• To explore the possibility of reducing concomitant steroid treatment
• To determine the long-term efficacy of 8 mg/kg tocilizumab (MRA) with regard to reduction in signs and symptoms
• To better understand and predict tocilizumab (MRA) efficacy, response, safety, progression of RA and associated diseases with regard to its effect on biomarkers |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•patients who have completed participation in the Phase III study WA17822 in adult rheumatoid arthritis.
•have been receiving methotrexate treatment.
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E.4 | Principal exclusion criteria |
•treatment with any investigational agent since the last administration of study drug in WA17822.
•treatment with iv gammaglobulin, plasmapheresis or Prosorba column since the last administration of study drug in WA17822.
•treatment with an anti-TNF of anti-IL1 agent, or a T cell costimulation modulator since the last administration of study drug in WA17822.
•previous treatment with any cell-depleting therapies.
•parenteral, intramuscular or intra-articular corticosteroids within 6 weeks prior to baseline in WA18695.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary parameters of interest are safety and long-term efficacy. The following endpoints will be summarized descriptively:
Safety:
• The safety of tocilizumab (MRA) with regard to adverse events and laboratory result abnormalities.
• Concomitant steroid treatment will be summarized by visit.
• Number of patients who withdraw from treatment.
Efficacy
• The proportion of patients achieving an ACR20, ACR50 and ACR70 response by visit.
• The proportion of patients who maintain an ACR20, ACR50 or ACR70 response consecutively for 24, 48, 96 and 264 weeks.
• The individual components of the ACR core set will be summarized by visit.
• Change in Disease Activity Score (DAS28) from baseline to weeks 24, 48, 96 and 264.
• The proportion of patients who are categorical DAS28 responders (EULAR response) at 24, 48, 96 and 264 weeks.
• The proportion of patients who remain categorical DAS28 responders (EULAR response) consecutively for 24, 48, 96 and 264 weeks. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety:
Throughout study
Efficacy:
1. At Week 24 (6 months)
2. At Week 48 (12 months)
3. At Week 96 (24 months)
4. At Week 264 (66 months) |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
Argentina |
Australia |
Austria |
Brazil |
Bulgaria |
Canada |
France |
Germany |
Hong Kong |
Hungary |
Israel |
Italy |
Mexico |
Singapore |
Slovakia |
Switzerland |
Thailand |
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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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The end of the trial will occur when the last participating patient completes the last scheduled visit, or when the sponsor decides to discontinue the development program. |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |