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 |
Patients with rheumatoid arthritis (RA) who are being treated with Disease Modifying Anti-Rheumatic Drugs (DMARDs) and have not had sufficient improvement in symptoms. |
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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 | 13.1 |
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) as monotherapy or in combination with background DMARD therapy(ies) 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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•patients who have completed participation in one of the core studies (e.g. WA17824, WA18062, WA18063, and WP18663) in adult rheumatoid arthritis.
•inadequate response to a stable dose of MTX or other allowable Disease Modifying Anti-Rheumatic Drug (DMARD).
•patients of reproductive potential must be using reliable methods of contraception.
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E.4 | Principal exclusion criteria |
•treatment with any investigational agent since the last administration of study drug in core studies.
•treatment with iv gamma globulin, plasmapheresis or prosorba column since the last administration of study drug in core studies.
•treatment with an anti-tumor necrosis factor agent or anti-IL-1 agent, or a T-cell costimulation modulator or any biologic since the last administration of study drug in the core studies. |
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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) by visit.
• The proportion of patients who remain categorical DAS28 responders (EULAR response) consecutively for 24, 48, 96 and 264 weeks.
• The proportion of patients who change from monotherapy to combination treatment by visit.
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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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 63 |
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 |
Belgium |
Brazil |
Canada |
China |
Costa Rica |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Hong Kong |
Iceland |
Israel |
Italy |
Lithuania |
Mexico |
Netherlands |
Norway |
Panama |
Peru |
Portugal |
Russian Federation |
Slovenia |
South Africa |
Spain |
Sweden |
Switzerland |
Thailand |
United Kingdom |
United States |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |