Moderately to severely active Rheumatoid Arthritis that has had an inadequate response or intolerance to conventional DMARD therapy including at least one TNF inhibitor MedDRA version: 17.0 Level: HLT Classification code 10039075 Term: Rheumatoid arthritis and associated conditions System Organ Class: 100000004870 MedDRA version: 17.0 Level: PT Classification code 10
Conditions
Sponsors
Boehringer Ingelheim International GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Must give written informed consent and be willing to follow the protocol. 2. Male or female participants, between 18 and 80 years of age, who have a diagnosis of moderately to severely active RA for at least 6 months as defined by at least six swollen joints (66 joint count) and at least eight tender joints (68 joint count) at Screening and Baseline (Day 1), and either an erythrocyte sedimentation rate (ESR) of > 28 mm/hour OR a CRP level > 1.0 mg/dL (normal: =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. ACR functional Class IV or wheelchair/bed bound. 2. Primary or secondary immunodeficiency (history of, or currently active), including known history of human immunodeficiency virus infection. 3. History of positive purified protein derivative test (positive tuberculosis [TB] test) without treatment for TB infection or chemoprophylaxis for TB exposure. 4. Positive HIV or TB at screening 5. Known coronary artery disease or significant cardiac arrhythmias or severe congestive heart failure (New York Heart Association classes III or IV), or interstitial lung disease observed on chest X-ray. 6. History of IgE-mediated or non-IgE-mediated hypersensitivity or known anaphylaxis to mouse proteins or a history of hypersensitivity to antibody therapy. 7. History of cancer including solid tumors, hematologic malignancies, and carcinoma in situ (except participants with previous resected and cured basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ Grade I cervical cancer within 5 years prior to the Screening Visit). 8. History of pancreatitis or current peptic ulcer disease. 9. Receipt of a live/attenuated vaccine within 12 weeks prior to the Screening Visit. 10. Any condition or treatment (including biologic therapies) that, in the opinion of the investigator, may place the patient at unacceptable risk during the trial. 11. Pregnancy or breast feeding. For women of childbearing potential, a positive serum pregnancy test at the Screening Visit and/or a positive urine pregnancy test at Baseline (Day 1). 12. History of, or current, inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or other systemic autoimmune disorder (e.g., systemic lupus erythematosus, inflammatory bowel disease, pulmonary fibrosis, or Felty's syndrome, scleroderma, inflammatory myopathy, mixed connective tissue disease, or any overlap syndrome). Hashimoto Thyroiditis, secondary Sjögren's syndrome or secondary limited cutaneous vasculitis with RA is permitted. 13. Diagnosis of juvenile idiopathic arthritis, also known as juvenile RA, and/or RA before age 16. 14. Any surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to the Screening Visit or planned within 24 weeks of the Screening Visit. 15. Lack of peripheral venous access. 16. Evidence of significant uncontrolled concomitant disease such as, but not limited to, nervous system, renal, hepatic, endocrine, or gastrointestinal disorders which, in the investigator's opinion, would preclude patient participation. 17. Known concurrent viral hepatitis or known positivity to HBe-ag, HBV DNA, HBV DNA polymerase, HCVRNA, anti HCV antibodies. 18. Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with IV anti-infectives within 4 weeks of the Screening Visit or completion of oral anti-infectives within 2 weeks of the Screening Visit. For exclusion criteria 19. - 32. see protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Evaluation of efficacy, safety and tolerability of BI 695500 and Rituxan/MabThera.;Main Objective: To show similarity of BI 695500 to MabThera and Rituxan and of Rituxan to MabThera with respect to PK (three-way PK similarity); Primary end point(s): Primary efficacy endpoints: Primary efficacy endpoints are the change from Baseline in DAS28 at 24 weeks and the proportion of patients meeting the ACR20 response criteria at Week 24 Primary PK endpoints: • AUC0-tz (area under the plasma concentration versus time curve from time zero to the last measurable concentration, determined over both dosages) • AUC0-8pred (area under the plasma concentration versus time curve from time zero to infinity, determined over both dosages). • AUC0-336 (area under the plasma concentration versus time curve from time zero to 336 hours) • observed Cmax (maximum plasma concentration, determined after the second drug infusion). ; Timepoint(s) of evaluation of this end point: Efficacy endpoints: at Week 24 PK endpoints: Will be assessed after the target of 150 patients have each completed 16 weeks in Part 1. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): DAS28 difference in mean change and ACR20 response rate. Physical examination, vital signs (blood pressure, pulse rate, respiratory rate, body temperature), 12-lead electrocardiogram, laboratory tests, adverse events and tolerability;Timepoint(s) of evaluation of this end point: Week 24/48 | — |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Estonia, France, Germany, Greece, Guatemala, Hungary, Ireland, Italy, Mexico, Netherlands, New Zealand, Norway, Peru, Poland, Portugal, Russian Federation, Serbia, South Africa, Spain, Sweden, Ukraine, United Kingdom, United States
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed