Rheumatoid Arthritis. MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Trade Name: Enbrel
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Etanercept
CAS Number: 185243-69-0
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: Group A Only 1a. Naïve to either etanercept or adalimumab, or who may have received prior anti-TNF therapy and displayed an intolerance but is now considered to be appropriate candidate for treatment with either etanercept or adalimumab. Inclusion Criteria: Group B Only 1b. History (as documented in the patient’s medical records) of initial clinical response to either etanercept or adalimumab and a subsequent loss of clinical response. Initial clinical response is defined as attainment of Good or Moderate response by EULAR criteria during the first 3 months of anti-TNF therapy; the consistency of the response must be documented on at least two consecutive occasions separated by at least 4 weeks. Loss of response to therapy is defined as DAS 28 score = 4.5 and increase or worsening in DAS 28 by = 1.2 from lowest DAS achieved on anti-TNF therapy, in at least two consecutive evaluations separated by at least 4 weeks. A documented loss of response is required prior to study screening. Confirmation of loss of response will occur at the Screening Visit. Inclusion Criteria: Groups A and B Able and willing to give written informed consent and comply with the requirements of the study protocol. Diagnosis of RA at least 3 months prior to start of anti-TNF therapy, according to the revised 1987 ACR criteria. Age 18–80 years, inclusive. If on corticosteroids, dose must be = 10 mg prednisone (or equivalent) for at least 2 weeks prior to baseline assessment. Must have inadequate response to MTX at a dose of 10-25 mg/week (po or parenteral) for = 12 weeks, of which the 4 weeks immediately prior to the baseline visit have been at a stable dose. Swollen joint count (SJC) = 4 (28 joint count), and tender joint count (TJC) = 4 (28 joint count) at baseline. At screening, either: CRP = 0.6 mg/dL (6 mg/L) with high sensitivity assay OR ESR = 28 mm/h At least one active joint that is appropriate for biopsy. Positive for rheumatoid factor (RF) or anti-CCP. If female, and of child-bearing potential, must agree to use a reliable form of contraception (e.g., hormonal contraceptive, patch, intra-uterine device, physical barrier) during the study and for 5 months following the last dose of prescribed anti-TNF therapy. If male, must agree to use (with his partner), a reliable form of contraception (hormonal contraceptive, patch, intra-uterine device, physical barrier method), during the study and for 5 months following the last dose of prescribed anti-TNF therapy. 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: Exclusion Criteria: Groups A and B Patients with any of the following will be excluded from the study: Any contraindication for entanercept or adalimumab treatment according to the approved product label. Pregnant or breast-feeding. History of or current inflammatory joint disease or autoimmune disease other than RA. Treatment with sulfasalazine, hydroxychloroquine, chloroquine, D-penicillamine, auranofin, azathioprine, cyclosporine, or tacrolimus = 4 weeks prior to baseline, or abatacept or leflunomide = 8 weeks before baseline. Treatment with any investigational agent = 4 weeks prior to baseline or < 5 half-lives of the investigational drug or where persisting PD effect (eg, cell depletion) of investigational therapy on target cells or pathways to RA (whichever is longer). Previous treatment with alkylating agents or cell-depleting therapies, including investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, anti-CD11a, Blys, BAFF, anti-CD22, and anti-CD20). Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline. Intra-articular or parenteral corticosteroids = 2 weeks prior to baseline. Intra-articular treatment of the joint selected for biopsy within 3 months of baseline visit. History of heart failure. Evidence of significant uncontrolled concomitant diseases such as neurological, cardiovascular, renal, hepatic, endocrine, or gastrointestinal disorders which, in the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to compare (i) baseline characteristics and (ii) changes over time in a)Ultrasonographic imaging of a discrete joint set including the joints selected for synovial biopsy b)Synovial tissue histology and immunohistochemistry (inflammation and phosphoprotein markers) c)Peripheral blood biomarkers of inflammation and tissue repair ;Secondary Objective: The secondary objectives of this study are to investigate the relationship between synovial pathology and ultrasonographic imaging parameters and to explore possible correlations between clinical efficacy and biologic effects of anti-TNF therapy on peripheral blood and synovial tissue biomarkers.; Primary end point(s): To compare (i) baseline characteristics and (ii) changes over time in: a) Ultrasonographic imaging of a discrete joint set including the joints selected for synovial biopsy. b) Synovial tissue histology and immunohistochemistry (inflammation and phosphoprotein markers). c) Peripheral blood biomarkers of inflammation and tissue repair | — |
Countries
Sweden, United Kingdom
Outcome results
None listed