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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Arthritis, Rheumatoid

Treatments: Drug: ofatumumab; Other: placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00686868

OFA110867

Details and patient eligibility

About

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.

Enrollment: 35 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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35 participants in 6 patient groups, including a placebo group

30mg

Experimental group

Description:

active

Treatment:

Drug: ofatumumab

3mg

Experimental group

Description:

active

Treatment:

Drug: ofatumumab

0.3mg

Experimental group

Description:

active

Treatment:

Drug: ofatumumab

placebo

Placebo Comparator group

Description:

placebo

Treatment:

Other: placebo

60mg

Experimental group

Description:

60mg

Treatment:

Drug: ofatumumab

100mg

Experimental group

Description:

100mg

Treatment:

Drug: ofatumumab