Study to Evaluate SC Route of Administration of Ofatumumab in RA Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT00686868
• Date of registration: 28/05/2008
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: Study to Evaluate SC Route of Administration of Ofatumumab in RA Patients
• Scientific title: Clinical Phase I/IIA Study of Subcutaneously Administration of Ofatumumab in Rheumatoid Arthritis Patients on Stable Dose Methotrexate
• Date of first enrolment: June 13, 2008
• Target sample size: 35
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00686868
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Participant).
• Phase: Phase 1

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Hungary, Italy, Netherlands, New Zealand, Poland, Russian Federation, Spain, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Key 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)



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Arthritis, Rheumatoid

Intervention(s)

Drug: ofatumumab

Other: placebo

Primary Outcome(s)

Safety and tolerability as described by the incidence and severity of adverse events [AEs], clinical laboratory parameters and vital signs. [Time Frame: throughout the study]

Secondary Outcome(s)

Immunogenicity as measured by the incidence, titre and type of human anti-human antibody (HAHA) immune response. [Time Frame: 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), [Time Frame: 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 [Time Frame: 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. [Time Frame: throughout study]

serum amyloid A (SAA), CD-3+, CD-4+ and CD-8+ lymphocytes or other biomarkers, as data permit. [Time Frame: 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, [Time Frame: 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. [Time Frame: throughout study]

Requirement for the use of pre-medication, including the timing, type and dose required. [Time Frame: throughout study]

Secondary ID(s)

OFA110867

Source(s) of Monetary Support

Please refer to primary and secondary sponsors