Study to Evaluate SC Route of Administration of Ofatumumab in RA Patients
- Registration Number
- NCT00686868
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This study will examine the safety and tolerability, PK and PD of subcutaneously administered GSK1841157 in patients with RA on stable dose Methotrexate. The study comprises a single dose escalation/de-escalation phase to investigate the minimal efficacious dose based on PD markers with an acceptable safety profile.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
Inclusion Criteria
- Male or female aged ≥ 18 years
- A diagnosis of rheumatoid arthritis according to the American College of Rheumatology (ACR1987 classification) of at least six months prior to screening
- Subjects must be treated with MTX, 7.5-25 mg/week, for at least 12 weeks prior to Visit 2, with the last 4 weeks prior to Day 2 at a stable dosage
- Patient must be willing to receive folic acid ≥5mg/wk 4 weeks prior to baseline administered according to locally accepted practice
- Body mass index (BMI) < 35kg/m2 (inclusive)
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
Key
Exclusion Criteria
- 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)
- 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)
- Exposure to etanercept < 4 weeks, infliximab or adalimumab < 8 weeks, or abatacept or anakinra < 12 weeks prior to visit 2
- Received any of the following treatments within 4 weeks prior to Visit 2:
- Anti-cancer therapy (e.g. alkylating agents, anti-metabolites, purine analogues, monoclonal antibodies)
- Glucocorticoid unless given in doses equivalent to ≤ 10 mg of prednisolone /day
- Intra-articular, i.m. or IV corticosteroids
- Live/attenuated vaccinations
- Cyclosporine
- Azathioprine
- Penicillamine
- Sulfasalazine
- Bucillamine
- Hydroxychloroquine
- Chloroquine
- Exposure to leflunomide within 12 weeks prior to visit 2 unless the subject has completed peroral cholestyramine treatment
- Exposure to gold therapy ≤ 12 weeks prior to Visit 2
- Exposure to IV immunogammaglobulins ≤ 24 weeks prior to Visit 2
- Past or current malignant melanoma
- 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
- History of significant cerebrovascular disease
- Positive plasma / white cell JC Virus (JCV) PCR (either compartment)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 0.3mg ofatumumab active 30mg ofatumumab active placebo placebo placebo 60mg ofatumumab 60mg 100mg ofatumumab 100mg 3mg ofatumumab active
- Primary Outcome Measures
Name Time Method Safety and tolerability as described by the incidence and severity of adverse events [AEs], clinical laboratory parameters and vital signs. throughout the study
- Secondary Outcome Measures
Name Time Method Requirement for the use of pre-medication, including the timing, type and dose required. throughout study Pharmacodynamics (B-cell depletion and re-population) as measured by CD-19 peripheral blood B- lymphocyte count via routine fluorescent activated cell sorting (FACS) analysis. throughout study Immunoglobulins (IgA, IgG, IgM), Complement (CH50, C3, C4), IgM Rheumatoid Factor (IgM-RF), IgA-RF and IgG-RF, anti-cyclic citrullinated peptide antibody (aCCP), throughout study PK/PD parameters including estimation of time to re-population of CD-19 peripheral blood B-cells to above LLQ (and/or <95% depletion) following single subcutaneous dose of Ofatumumab. throughout study Immunogenicity as measured by the incidence, titre and type of human anti-human antibody (HAHA) immune response. throughout study Other pharmacodynamic/biomarkers of disease activity and immune status may include high sensitivity C-reactive protein (hsCRP), Erythrocyte Sedimentation Rate (ESR), B-Lymphocyte Stimulator (BLyS/BAFF), B-Lymphocyte Chemokine (BLC), IL-6, throughout study serum amyloid A (SAA), CD-3+, CD-4+ and CD-8+ lymphocytes or other biomarkers, as data permit. throughout study Pharmacodynamics (B-cell depletion and re-population) as measured by CD-19 peripheral blood B- lymphocyte count via routine FACS analysis.Other Secondary Endpoints throughout study
Trial Locations
- Locations (1)
GSK Investigational Site
🇪🇸Madrid, Spain