| 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 TCZ monotherapy and TCZ + MTX combination therapy, versus MTX monotherapy, with regard to the following primary endpoint in patients with early, moderate to severe rheumatoid arthritis (RA):- Proportion of patients who achieve DAS28 remission (DAS28 < 2.6) at 6 months. |
|
| E.2.2 | Secondary objectives of the trial |
| Prevention of structural joint damage over 12 months and maintenance of this effect at 24 months; Improvement in physical function over 12 months and maintenance of this effect at 24 months; Pharmacokinetics, immunogenicity and pharmacodynamics of TCZ in patients with early RA; Safety and efficacy of TCZ administration in patients with early RA . |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Able and willing to give written informed consent and comply with the requirements of the study protocol. 2. Patients with rheumatoid arthritis of ≤ 2 years duration at the time of baseline visit, diagnosed according to the revised 1987 American College of Rheumatology (ACR; formerly American Rheumatism Association) criteria. 3. Receiving treatment on an outpatient basis. 4. No previous MTX or biologic agent. 5. DMARDs should be withdrawn at least 2 weeks prior to baseline (leflunomide for > 12 weeks or ≥ 14 days after standard cholestyramine or activated charcoal washout, azathioprine for ≥ 4 weeks). 6. DAS28 > 3.2 at screening and baseline visits. 7. Swollen joint count (SJC) ≥ 4 (66 joint count), and tender joint count (TJC) ≥ 6 (68 joint count) both at screening and baseline visits. 8. At screening either CRP ≥ 10 mg/L (≥ 1 mg/dL ) or ESR ≥ 28 mm/hr. 9. At screening, positive Rheumatoid Factor or Anti-CCP Ab or if negative for Rheumatoid Factor and Anti-CCP Ab at screening ≥ 1 erosion of hands, wrists or feet (the erosion(s) will be determined by central reading). 10. Radiographs of hands, wrists and feet must be of sufficient quality as determined by central reader imaging laboratory according to the procedure manual for radiographic examinations and the Imaging Review Charter 11. Age ≥ 18 years. 12. Weight ≤ 150 kg. 13. Oral corticosteroids (≤ 10 mg/day prednisone or equivalent) if the dose has been stable for at least 4 weeks prior to baseline. 14. NSAIDs if the dose has been stable for at least 2 weeks prior to baseline. 15. Must be willing to receive oral folate. 16. Females of child-bearing potential and non sterilized males with female partners of child-bearing potential may participate in this trial only if using a reliable means of contraception (e.g. physical barrier (patient and partner), contraceptive pill or patch, spermicide and barrier, or IUD). 17. If female and of childbearing potential, the patient must have a negative serum pregnancy test within three weeks prior to baseline. |
|
| E.4 | Principal exclusion criteria |
| General: 1. Major surgery (including joint surgery) within eight weeks prior to screening or planned major surgery within six months after baseline. 2. Rheumatic autoimmune disease other than RA, including SLE, MCTD, scleroderma, and polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty s syndrome). Secondary Sj�grens syndrome or nodulosis with RA is permitted. 3. Functional class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis. 4. Prior history of or current inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease). Excluded Previous or Concomitant Therapy: 5. Treatment with MTX at any time prior to baseline. 6. Treatment with a biologic agent at any time prior to baseline. 7. Treatment with any investigational agent within four weeks (or five half-lives, whichever is longer) of screening visit. 8. Previous treatment with any cell depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20). 9. Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within six months of baseline visit. 10. Intraarticular or parenteral corticosteroids within six weeks prior to screening visit. 11. Immunization with a live/attenuated vaccine within four weeks prior to baseline visit. 12. Previous treatment with TCZ. 13. Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil or with total lymphoid irradiation. Exclusions for General Safety: 14. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. 15. Current or previous (within the past 2 years) evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or gastrointestinal disease. 16. Uncontrolled disease states, such as asthma or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids. 17. History of diverticulitis, diverticulosis requiring antibiotic treatment or chronic ulcerative lower GI disease such as Crohn s disease, ulcerative colitis or other symptomatic lower GI conditions that might predispose to perforations. 18. Current liver disease as determined by the investigator. Et al... |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of patients achieving DAS28 remission (DAS28 < 2.6) 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 | No |
| 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 | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Test di immogenicita`, valutazione della qualita` della vita |
|
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 15 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 90 |
| 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 | 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
|
| La fine dello studio coincidera` con la LPLV o con la decisione dello Sponsor di interrompere il programma di sviluppo del farmaco. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
Print
