Rheumatoid Arthritis
Conditions
Sponsors
Wyeth Research Division of Wyeth Pharmaceuticals Inc., Clinical Research and Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Meet American College of Rheumatology (ACR) criteria for RA. 2. Have active RA consisting of = 5 swollen and = 5 painful joints (28-joint count) and at least 1 of the following 3: erythrocyte sedimentation rate (ESR) (Westergren) = 28 mm/hour; C-reactive protein (CRP) >= 15 mg /L; or morning stiffness = 45 minutes at both screening and baseline (CRP value obtained from screening visit may be used to meet this criteria). 3. ACR functional class I to III. 4. Disease duration of at least 6 months. 5. Disease onset at > 16 years of age. 6. Age 18 to 75 years. 7. Must be currently treated with a stable, well-tolerated dose of MTX (7.5 to 20 mg) given once weekly for at least 12 weeks before the baseline visit. 8. Women of childbearing potential, who have a negative pregnancy test result, as well as all male subjects, must agree to use a medically acceptable method of birth control during the study and for at least 12 weeks after the last dose of test article. 9. Be able and willing to comply with study visits and procedures specified in this protocol. 10. Understand, sign, and date the written voluntary informed consent form at the screening visit before any protocol-specific procedures are performed. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Screening Visit 1. Any prior use of anti-TNF alpha biologics, rituximab, receipt of anti-CD4 or diphtheria interleukin-2 fusion protein or other immunosuppressive biologics (except for anakinra). 2. Pregnant or breastfeeding women or women planning to become pregnant during the study or within 12 weeks after the last dose of test article. 3. History of poor compliance or history of drug abuse/alcohol abuse, excessive alcohol beverage consumption or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent. 4. Any condition that the physician judges could be detrimental to subjects participating in this study, including any clinically important deviations from normal clinical laboratory values or important concurrent medical events, as detailed in the protocol body. Baseline Visit 1. Within 12 weeks before baseline, a change in dose of MTX. 2. Within 4 weeks before baseline, current use of more than 1 nonsteroidal anti-inflammatory drug (NSAID) or change of dose of the NSAID or NSAID use greater than the maximum recommended dose. 3. Within 4 weeks before baseline, use of more than 10 mg/day of prednisone or equivalent or change in the dose of prednisone or equivalent. 4. Within 4 weeks before baseline, receipt of an intra-articular corticosteroid injection or bolus intramuscular or intravenous treatment with corticosteroids (> 20 mg prednisone or equivalent). 5. Within 4 weeks before baseline, receipt of the following DMARDs: hydroxychloroquine, chloroquine, sulfasalazine, auranofin, and intramuscular gold, cyclosporine, azathioprine, leflunomide, D-penicillamine and anakinra. 6. Within 4 weeks before baseline, receipt of any investigational drug or investigational biological agent. Within 12 weeks before baseline, receipt of an investigational agent that is unknown. 7. Within 8 weeks before baseline, receipt of any live (attenuated) vaccines. 8. Within 24 weeks before baseline, receipt of cyclophosphamide.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy and the safety of 3 dose levels of oral TMI-005 in comparison with placebo in subjects with active RA who have been receiving stable doses of MTX.;Secondary Objective: 1. To compare the efficacy and the safety of TMI-005 among 3 dose levels. 2. To assess health outcome measures. 3. To assess ACR 20, ACR 50, and ACR 70 responses at all time points and components of ACR response criteria. 4. To assess disease activity score-28 (DAS-28). 5. To assess other measures of disease activity. 6. To assess population pharmacokinetics (PK) of TMI-005. 7. To search for biomarkers that may correlate with severity of RA and/or clinical response to TMI-005 using peripheral blood mononuclear cells (PBMC) gene expression and, possibly, protein expression profiling in a subset of subjects at selected sites.;Primary end point(s): Efficacy The primary efficacy variable is the ACR 20 response rate at Week 12. Safety Spontaneously reported signs and symptoms. Scheduled physical examinations (evaluation of shoulder abduction, body weight measurements). Elicited history reported by subjects. Vital sign measurements. 12-lead electrocardiogram (ECG). Posteroanterior (PA) and lateral chest radiographs. Clinical laboratory evaluations. More frequent safety evaluations may be performed if clinically indicated, or at the discretion of the investigator. Monitor all adverse events (AEs). | — |
Countries
Czech Republic, Estonia, Italy
Outcome results
None listed