| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 determine the number of patients in clinical remission at 12 months of follow-up, as defined as the absence of symptoms and signs of inflammatory arthritis. |
|
| E.2.2 | Secondary objectives of the trial |
1. The number of patients in clinical remission at 18 months (as defined as absence of symptoms and signs of clinical arthritis)
2. Conventional disease activity measures (VAS pain/fatigue/global/physician, EMS, TJC, SJC, CRP, ESR)
3. Functional, work and quality of life assessments (HAQ, WIS, WDA, EQ-5d, SF-36)
4. Proportion of patients achieving 6 months of remission
5. Disease Activity Score (DAS) 28
6. The number of patients in drug-free remission at 12 and 18 months
7. The number of patients in etanercept-free remission at 12 and 18 months (ETN arm)
8. Remission by ACR Criteria
9. To compare the effects of the combination of ETN and MTX to MTX alone on radiographic change at 12 months and 18 months
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Is age 18 -80 years
2. Patients have articular synovitis, within 3 months of diagnosis (Synovitis is defined as the presence of soft tissue swelling and atleast 1 of the following 2 criteria: tenderness or decreased range of motion)
3. Either RF antibody (+) or anti-CCP antibody (+) or SE (+)
4. Demonstrates a negative serum pregnancy test at screening if female of childbearing potential. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. Sexually active women participating in the study must use a medically acceptable form of contraception during the study and for 3 months after the last dose of study medications. Medically acceptable forms of contraception for women include oral contraception, injectable or implantable methods, intrauterine devices, or properly used barrier contraception
5. Agrees to use a medically accepted form of contraception during the study and for 3 months after the last dose of study drug, if sexually active male. Medically acceptable forms of contraception for males are a properly used barrier contraceptive or sterilization.
6. Is capable of understanding and signing an informed consent form
7. Is able and willing to self-inject study drug or have a designee who can do so
8. Is able and willing to take oral medication
9. Is able to store injectable test article at 2„a C to 8„a C
10. Demonstrates a negative tuberculosis screening test |
|
| E.4 | Principal exclusion criteria |
1. Received previous treatment with any DMARDS
2. Received previous treatment with ETN or other tumour necrosis factor (TNF) antagonist (e.g. a TNF monoclonal antibody or a soluble TNF receptor)
3. Previous treatment with IL-1 receptor antagonist
4. Chronic arthritis diagnosed before 16 years old
5. Received any investigational ¡§biological¡¨ agent within 3 months of screening visit
6. Received treatment with any investigational drug of ¡§chemical¡¨ nature within one month prior to study screening
7. Known Human Immunodeficiency Virus (HIV)
8. Presence of any contraindication to ETN or MTX
9. Has significant concurrent medical diseases including uncompensated congestive heart failure, myocardial infarction within 12 months, unstable angina pectoris, uncontrolled hypertension, severe pulmonary disease, or history of human immunodeficiency virus (HIV) infection, immunodeficiency syndromes, central nervous system (CNS) demyelinating events suggestive of multiple sclerosis, renal or gastrointestinal conditions, which in the opinion of the investigator places the subject at an unacceptable risk for participation in the study.
10. Has cancer or a history of cancer (other than resected cutaneous basal cell carcinoma, and in situ cervical cancer) within 5 years of entering the screening period.
11. Current crystal or infective arthritis
12. Chronic infection of the upper respiratory tract (eg,. Sinusitis), chest (eg. Bronchiectatic lung disease), urinary tract or skin (eg. Paronychia, chronic ulcers, open wounds)
13. Any ongoing or active infection or any major episode of infection requirimg hospitalization or treatment with IV antibiotics within the preceeding 30 days and/or orally administered antibiotics in the preceeding 15 days.
14. Demonstrates liver function abnormality (aminotransferase [AST] / alanine aminotransferase [ALT] > 2x upper limit of normal [ULN]) or bilirubin >51umol/L.
15. Has renal disease (creatinine level > 133 ƒÝmol/L)
16. Has leukopenia (white blood cells < 3000 x 106/L)
17. Has thrombocytopenia (platelets < 125 x 109/L)
18. Has a hemoglobin level of < 9g/L for males and < 85 g/L for females
19. Is pregnant or breast-feeding
20. Joint surgery within preceeding 2 months (at joints to be assessed within this study)
21. Received anti-CD4, diphtheria interleukin-2 fusion protein, anti interleukin-6 (anti-IL-6), rituxamab or other immunosuppressive biologic during the last 6 months before screening, and treatment with such agents more than 6 months before screening if there are persistent signs of immunosuppression (with a subsequent abnormal absolute T-cell count) at screening visit
22. Received any live (attenuated) vaccines within 4 weeks of screening visit
23. Received cyclophosphamide within 6 months of screening visit
24. Received bolus intra-articular/intravenous treatment with corticosteroids (> 20 mg prednisone or equivalent) within 12 weeks of screening visit
25. Uses a dose of NSAID greater than the maximum recommended dose in the product information at the screening visit
26. Has a history of confirmed blood dyscrasia
27. Has any condition judged by the physician to cause this study to be detrimental to the subject
28. Has a history of drug abuse or psychiatric disease that would interfere with the ability to comply with the study protocol
29. Has a history of alcohol abuse or excessive alcohol beverage consumption
30. Has a history of known liver cirrhosis, fibrosis, or fatty liver
31. Has a history of any viral hepatitis within 1 year of screening |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| clinical remission at 12 months of follow-up |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| 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 | Yes |
| E.8.1.2 | Open | No |
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| 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.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | |
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