Rheumatoid Arthritis MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Name: Ofatumumab
Product Code: GSK1841157
Pharmaceutical Form: Concentrate for solution for injection
Current Sponsor code: GSK1841157
Other descriptive name: HuMax-CD20
Concentration unit: mg
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female aged = 18 years. 2. A diagnosis of rheumatoid arthritis according to the American College of Rheumatology (ACR1987 classification) of at least six months prior to screening. 3. Subjects must be treated with MTX, 7.5-25 mg/week, for at least 12 weeks prior to Visit 2 (study day 1), with the last 4 weeks prior to Day 2 (study day 1) at a stable dosage. 4. Patient must be willing to receive folic acid =5 mg/week starting 4 weeks prior to baseline (Visit 2) until the last visit, administered according to locally accepted practice. 5. Body mass index (BMI) =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects with a history of a rheumatic autoimmune disease other than RA (except secondary Sjögren's syndrome), or with significant systemic involvement secondary to RA (vasculitis, pulmonary fibrosis or Felty's syndrome). 2. Previous exposure to biologic cell depleting anti-rheumatic therapies, including investigational compounds (e.g. anti-CD11a, anti-CD19, anti-CD20, anti-CD22, anti-BLyS/BAFF, anti-CD3, anti-CD4, anti-CD5, anti-CD52. 3. Exposure to etanercept 5 years 10. Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, renal infection, chest infection with bronchiectasis, tuberculosis and active hepatitis B and C. • Screening for TB will be done in accordance with local guidelines including Mantoux testing, and if necessary follow-up with QuantiFERON testing for patients whose history of immunization with BCG cannot be documented. • Patients with a negative test OR a positive Mantoux test and a negative QFT-G test are eligible for inclusion into the study. • Patients with a positive Mantoux test without QFT-G negativity are excluded. Additionally, patients with documented BCG vaccination will be exempted from the Mantoux test assessment. 11. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from screening, congestive heart failure, known QT abnormalities, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities. 12. Significant concurrent, uncontrolled medical condition including, but not limited to, PML, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral psychiatric disease, or evidence of demyelinating disease. 13. History of significant cerebrovascular disease. 14. Known HIV positive. 15. Screening laboratory values (according to central laboratory): • Hemoglobin 3 times the upper limit of normal • S-AST > 3 times the upper limit of normal • S-ALP > 2 times the upper limit of normal • S-creatinine > 133 µmol/L (1.5 mg/dL) 16. Positive serology for hepatitis B (HB) defined as: • Positive test for HBsAg. If negative, Hep B serology negativity will be confirmed by: • Negat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Part A-Key secondary objectives 1) To identify and characterize requirement for pre-medication with systemic steroids in association with subcut ofatumumab in patients with rheumatoid arthritis. 2) To explore the pharmacodynamic dose-response curve for subcut ofatumumab. 3) To determine the minimum dose of ofatumumab that results in target level of depletion of peripheral blood B- lymphocytes after single subcut. administration. Target level is defined as >95% or to below LLQ, as measured by change from baseline at week 4 and/or the median value across weeks 2-4. 4) To characterize the PK/PD relationship following single subcut. dose of ofatumumab. Part B Key secondary objectives 1) To characterize the safety & tolerability of ofatumumab administered as two subcut. doses. 2) To determine the observed time to re-population of CD-19+ peripheral blood B-lymphocytes (cell counts 95% depletion of peripheral blood B-lymphocytes in patients with rheumatoid arthritis. | — |
Countries
Belgium, France, Germany, Spain
Outcome results
None listed