Early Inflammatory Arthritis Musculoskeletal Diseases Arthritis
Conditions
Interventions
Etanercept and methotrexate versus placebo and methotrexate.
Sponsors
University of Leeds (UK)
Eligibility
Inclusion criteria
Inclusion criteria: Subject must fulfill all of the following conditions or characteristics in order to be considered for study enrolment or participation: 1. Aged 18 to 80 years 2. Patients have articular synovitis, within three months of diagnosis (synovitis is defined as the presence soft tissue swelling and at least one of the following two criteria: tenderness or decreased range of motion) 3. Either Rheumatoid Factor (RF) antibody (positive) or Anti-Cyclic Citrullinated Peptide (Anti-CCP) antibody (positive) or Shared Epitope (SE) (positive) 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 three 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 three 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 sterilisation 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°C to 8°C 10. Demonstrates a negative tuberculosis screening test
Exclusion criteria
Exclusion criteria: Subjects with any of the following conditions or characteristics will be excluded from study enrolment: 1. Received previous treatment with any Disease Modifying Anti-Rheumatic Drugs (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 Interleukin-1 (IL-1) receptor antagonist 4. Chronic arthritis diagnosed before 16 years old 5. Received any investigational ?biological? agent within three 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 five years of entering the screening period 11. Current crystal or infective arthritis 12. Chronic infection of the upper respiratory tract (e.g., sinusitis), chest (e.g., bronchiectatic lung disease), urinary tract or skin (e.g., paronychia, chronic ulcers, open wounds) 13. Any ongoing or active infection or any major episode of infection requiring hospitalisation or treatment with intravenous (IV) antibiotics within the preceding 30 days and/or orally administered antibiotics in the preceding 15 days 14. Demonstrates liver function abnormality (Aspartate Transaminase [AST]/Alanine Transaminase [ALT] more than 2 x Upper Limit of Normal [ULN]) or bilirubin more than 51 µmol/L 15. Has renal disease (creatinine level more than 133 µmol/L) 16. Has leukopaenia (white blood cells less than 3000 x 10^6/L) 17. Has thrombocytopaenia (platelets less than 125 x 10^9/L) 18. Has a haemoglobin level of less than 9 g/L for males and less than 85 g/L for females 19. Is pregnant or breast-feeding 20. Joint surgery within preceding two months (at joints to be assessed within this study) 21. Received anti-CD4, diphtheria Interleukin-2 (IL-2) fusion protein, anti-Interleukin-6 (anti-IL-6), rituxamab or other immunosuppressive biologic during the last six months before screening, and treatment with such agents more than six 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 four weeks of screening visit 23. Received cyclophosphamide within six months of screening visit 24. Any corticosteroids within 28 days prior to screen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the number of patients in clinical remission at 12 months, as defined as the absence of symptoms and signs of inflammatory arthritis (i.e., Swollen Joint Count [SJC] zero; Tender Joint Count [TJC] zero). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The number of patients in clinical remission at 18 months (as defined as absence of symptoms and signs of clinical arthritis i.e., SJC zero; TJC zero) 2. Conventional disease activity measures (Visual Analogue Scale [VAS] pain/fatigue/global/physician, Early Morning Stiffness (EMS), TJC, SJC, C-Reactive Protein [CRP], Erythrocyte Sedimentation Rate [ESR]) 3. Functional, work and quality of life assessments (Health Assessment Questionnaire [HAQ], WIS, WDA, EuroQoL [EQ-5d] instrument, Short Form health survey [SF-36]) 4. Proportion of patients achieving 26 weeks 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 American College of Rheumatology (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 | — |
Countries
United Kingdom
Outcome results
None listed