None listed
Conditions
Interventions
Group A Type of group
PF-05280586 1000 mg, IV on days 1 and 15
Group name:Group C Type of group
Rituximab US 1000 mg, IV on days 1 and 15
Sponsors
PFIZER S.A.,
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Age 18 years or oIder. 2. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study. 3. Willing and able to compIy with scheduled visits, treatment plan, laboratory tests, and other study procedures. 4. Confirmed diagnosis of rheumatoid arthritis (RA) based on 2010 American College Of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis (see Appendix 1). 5. Meets Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA (see Appendix 2). 6. RA seropositivity as documented by a screening assessment for RF, and/or anti-CCP. 7. Active disease as defined by: a. ≥ 6 tender/painful joints (of 68 assessed) at screening and baseline, and b. ≥ 6 swollen joints (of 66 assessed) at screening and baseline, and c. hs-CRP > ULN at screening, performed by centrallaboratory OR Patient´s Global Assessment of Arthritis score ≥ 50, and d. Baseline DAS28-CRP >3.2.
Exclusion criteria
Exclusion criteria: 1. Any prior treatment with lymphocyte depleting therapies such as, but not limited to rituximab [Rituxan®, MabThera®], alemtuzumab (Campath®), totallymphoid irradiation. 2. Pregnant females; breast feeding females; males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 6 months after last dose of investigational product. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active. 3. Inadequate bone marrow, liver, renal and immune system functions at screening visit as defined by: a. Absolute neutrophil count (ANC) ≤ 1500 cells/mm³. b. Platelets <100 x 109/L. c. Hemoglobin (Hgb) <8 g/dL. d. Bilirubin ≥ 1.5 times the upper limit of normal (x ULN), unless a diagnosis of Gilbert´s Disease in which case ≥ 2.5 x ULN. e. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≥ 3 x ULN. f. Serum creatinine ≥ 1.5 mg/dL. g. Immunoglobulin G (IgG) or IgM < lower limit of normal (LLN). 4. Evidence of latent, inadequately treated or active infection with tuberculosis (TB) as defined by one or more of the following: a. Screening TB according to local health authority guidance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Cmax is the peak serum concentration of study drug (rituximab) after a dose has been administered. Measure:Maximum Serum Concentration (Cmax) of Rituximab Timepoints:Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion ; Outcome name:The AUC 0-inf refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) extrapolated to infinity. Measure:AUC 0-inf of Rituximab Timepoints:Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:The AUC 0-2wk refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) to 2 weeks after drug administration. Measure:Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk) Timepoints:Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion ; Outcome name:The AUC 0-T refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) to the last measured concentration at time T. Measure:Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T) Timepoints:Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion ; Outcome name:The AUC 0-T,B-cell refers to the concentration in serum of B-cells. It represents the total B-cells over time from time 0 (the point of drug administration) to the last measurement taken at time T. Measure:CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell) Timepoints:Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT) ; Outcome name:The lowest CD19+ B-cell count measured in a participants blood post-baseline. Measure:Minimum Post-Baseline CD19+ B-cell Count (/uL) Timepoints:Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT) ; Outcome name:The amount of time in weeks from baseline to the lowest observed CD19+ B-cell count. Measure:Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks) Timepoints:Baseline and Weeks 2, 3, 5, 9, 13, 17, | — |
Countries
Australia, Canada, Colombia, Germany, Israel, Mexico, Russian Federation, South Africa, United Kindgdom, United States
Contacts
Public ContactFlor Luna
PFIZER S.A.
Outcome results
None listed