Early rheumatoid arthritis Musculoskeletal Diseases Early rheumatoid arthritis
Conditions
Interventions
Patients will be randomised into one of following groups to receive:
1. Adalimumab (ADA) and MTX over 24 weeks followed by MTX monotherapy up to week 48
2. MTX monotherapy and placebo
All subjects wi
Sponsors
Charité - University Medicine Berlin (Germany)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each patient must meet all of the following inclusion criteria to be enrolled into this study: 1. Patients with definite RA referring to the American College of Rheumatology (ACR) Classification Criteria of 1987 up to one year after first RA symptoms 2. Aged 18 to 70 years 3. Has active disease at the time of randomisation as indicated by: six from 68 tender and six from 66 swollen joints and at least one of the following two criteria: 3.1. Westergren erythrocyte sedimentation rate (ESR) of 28 mm/hour 3.2. C-reactive protein (CRP) levels more than 1.0 mg/dl 4. Has morning stiffness for longer than 30 minutes 5. No current or prior therapy with Disease Modifying Anti-Rheumatic Drugs (DMARDs) or biologics 6. Non steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids treatment has to be stable two weeks prior to screening and during the trial with maximal less than or equal to 10 mg/d prednisolone equivalent 7. Is capable of understanding and signing an informed consent form 8. Is able and willing to self-inject study drug or have a designee who can do so 9. Is able and willing to take oral medication 10. Is able to store injectable test article at 2°C to 8°C 11. Sexually active women participating in the study must use a medically acceptable form of contraception for women. This includes oral contraception, injectable or implantable methods, intrauterine devices, or properly used barrier contraception
Exclusion criteria
Exclusion criteria: Patients meeting any following exclusion criteria are not to be enrolled in this study: 1. Has significant concurrent medical diseases including cancer or a history of cancer (other than resected cutaneous basal and squamous cell carcinoma, in situ cervical cancer) in the last five years 2. Has 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 syndrome, other rheumatologic diseases than RA, or central nervous systems demyelinating events suggestive or multiple sclerosis 3. Received anti-CD4, diphtheria interleukin-2 fusion protein, anti-interleukin-6, rituximab or other immunsuppressive biologic before screening, and treatment with such agents if there are persistent signs of immunosuppression (with a subsequent abnormal absolute T-cell count) at screening count 4. Received any live (attenuated) vaccines within four weeks of screening visit 5. Received intra-articular corticosteroid injection within four weeks of screening 6. Received bolus intramuscular/intravenous treatment with corticosteroids (more than 10 mg prednisone or equivalent) within four weeks of screening visit 7. Is taking more than 10 mg/d prednisone or equivalent 8. Has a history of confirmed blood dyscrasias 9. Has a significant active infection or any underlying diseases that could predispose subjects to infections (e.g. history of recurring infections, leg ulcers, advanced or poorly controlled diabetes) 10. Has active infection with Hepatitis A, B or C virus, tuberculosis, chronic infections, latent tuberculosis (has to be excluded by Chest X-ray and Purified Protein Derivative [PPD] Test according to Mendel-Mantoux), in case of latent tuberculosis isoniazid 300 mg for ten months, starting one month prior to treatment is obligatory 11. Has renal disease (creatine level more than 175 µmol/L) or a history of known liver cirrhosis, fibrosis 12. Has an abnormal liver function (aspartate aminotransferase [AST], gamma-glutamyl transpeptidase [GGT], alanine aminotransferase [ALT] two times the upper limit of normal [ULN]) 13. Has a history of psychiatric disease that would interfere with the ability to comply with the study protocol 14. Is pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy is primary measured with the Disease Activity Score 28 (DAS 28) at week 48. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To evaluate DAS 28 at week 24 2. The partial-remission (DAS 28 less than 2.6) at week 24 and 48 3. The duration of clinical remission during the trial 4. The variables of the World Health Organization (WHO)/International League of Associations for Rheumatology (ILAR) core set for clinical trials (DAS 28, Health Assessment Questionnaire [HAQ]) 5. To evaluate ACR 20, ACR 50 and ACR 70 values from baseline to week 24 6. To evaluate ACR 20, ACR 50 and ACR 70 values from baseline to week 48 7. The change in ACR 20, ACR 50 and ACR 70 values response between week 24 to week 48 8. The radiographic change (X-ray of hands and feet in two dimensions) from baseline to week 48 by central assessment by the modifyed Sharp-Score and Ratingen Score 9. Descriptive analysis of change glucocorticoid, NSAIDs/Coxib dosage 10. Report on adverse events and serious adverse events (referring to International Conference on Harmonisation guidelines on Good Clinical Practice [ICH GCP]/Committee for Proprietary Medicinal Products International Conference on Harmonisation guidelines on E2: Clinical Safety [CPMP ICH E2]). | — |
Countries
Germany
Outcome results
None listed