E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
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 |
|
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 efficacy of treatment with 162 mg TCZ given subcutaneously (SC) weekly versus 8 mg/kg TCZ given intravenously (IV) every 4 weeks with regard to non-inferiority of the proportion of patients who achieve ACR20 at Week 24. - The safety of treatment with 162 mg TCZ given SC weekly versus 8 mg/kg TCZ given IV every 4 weeks, with regard to AEs and laboratory assessments. |
|
E.2.2 | Secondary objectives of the trial |
- Long-term safety and efficacy - Pharmacokinetics (PK) and pharmacodynamics (PD) of TCZ following SC administration - Immunogenicity of TCZ following SC administration - Effect of IV to SC switch on the safety, efficacy, PK and PD of TCZ |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOCINETICA/FARMACODINAMICA: Versione:A Data:2010/04/28 Titolo:A randomized, double-blind, parallel group study of the safety and effect on clinical outcome of tocilizumab SC versus tocilizumab IV, in combination with traditional disease modifying anti-rheumatoid arthritis drugs (DMARDs), in patients with moderate to severe active rheumatoid arthritis - Substudies PK-PD Obiettivi:- Sottostudio di Farmacocinetica/Farmacodinamica (PK/PD) nella fase in doppio cieco: determinare PK e PD (sIL-6R e IL-6)dopo somministrazione di Tocilizumab sottocute (SC), nelle 24 settimane in doppio cieco; - Sottosudio di Farmacocinetica (PK)nella fase in aperto: stabilire l`effetto sulla farmacocinetica di Tocilizumab nel passaggio dal trattamento endovenoso (EV) a quello sottocute (SC) nella fase in aperto, durante la Settimana 25 e la 26.
|
|
E.3 | Principal inclusion criteria |
Able and willing to give written informed consent and comply with the requirements of the study protocol (e.g. willing to take oral folate at a minimum dose of 5 mg/week if on MTX treatment.) 2. Age ������ 18 years 3. Rheumatoid arthritis of ������ 6 months duration, diagnosed according to the revised 1987 American College of Rheumatology (ACR; formerly American Rheumatism Association) criteria, Appendix 2) 4. Receive treatment on an outpatient basis. 5. Swollen joint count (SJC) ������ 4 (66 joint count) and tender joint count (TJC) ������ 4 (68 joint count) at screening and baseline. 6. Prior to randomization, will have discontinued etanercept for ������ 2 weeks, infliximab, certolizumab, golimumab, abatacept or adalimumab for ������ 8 weeks, anakinra for ������ 1 week. 7. Have received permitted DMARDs at a stable dose for at least 8 weeks prior to baseline. 8. At screening CRP ������ ULN (central laboratory). 9. Oral corticosteroids (������ 10 mg/day prednisone or equivalent) and NSAIDs (up to the maximum recommended dose) are permitted if on a stable dose regimen for ������ 4 weeks prior to baseline. 10. Females of childbearing potential and males with female partners of childbearing potential may participate in this trial only if using a reliable means of contraception (e.g. physical barrier (patient or partner), contraceptive pill or patch, spermicide and barrier, or IUD). 11. If female of childbearing potential, the patient must have a negative pregnancy test at screening and baseline visit. |
|
E.4 | Principal exclusion criteria |
1. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization. 2. Rheumatic autoimmune disease other than RA, including SLE, MCTD, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty’s syndrome). Secondary Sj�gren’s syndrome with RA is allowable. 3. Functional class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis (Appendix 3). 4. Diagnosis of juvenile idiopathic arthritis (JIA) or juvenile rheumatoid arthritis (JRA) and/or RA before the age of 16. 5. Prior history of or current inflammatory joint disease other than RA (e.g., gout, Lyme disease, seronegative spondyloarthropathy including reactive arthritis, psoriatic arthritis, arthropathy of inflammatory bowel disease). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of patients achieving an ACR 20 at Week 24. |
|
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
esplorazione dei biomarcatori (DNA e non-DNA); valutazioni di immunogenicita` |
|
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 | 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 | Yes |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Stesso farmaco con forma farmaceutica diversa |
|
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 |
|
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
| |
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 | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |