E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
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. |
|
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 |
|
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. |
|
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
|
|
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. |
|
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
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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. |
|
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. |
|
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) |
|
E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
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) | 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
| 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 | 2 |
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 |
|
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
|
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 |
|
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |