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

Clinical Phase I/IIA Study of Subcutaneously Administration of Ofatumumab in Rheumatoid Arthritis Patients on Stable Dose Methotrexate

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.

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Other: placebo; Drug: ofatumumab

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • GSK Investigational Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • GSK Investigational Site
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • GSK Investigational Site
    • Melbourne, Victoria, Australia, 3004
      • GSK Investigational Site
• Belgium
  • Brussels, Belgium, 1200
    • GSK Investigational Site
  • Leuven, Belgium, 3000
    • GSK Investigational Site
• France
  • Echirolles, France, 38130
    • GSK Investigational Site
• Italy
  • Veneto
    • Verona, Veneto, Italy, 37126
      • GSK Investigational Site
• New Zealand
  • Christchurch, New Zealand, 8011
    • GSK Investigational Site
• Poland
  • Bydgoszcz, Poland, 85168
    • GSK Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 115522
    • GSK Investigational Site
  • Ryazan, Russian Federation, 390026
    • GSK Investigational Site
  • Smolensk, Russian Federation, 214018
    • GSK Investigational Site
  • Yaroslavl, Russian Federation, 150003
    • GSK Investigational Site
• Spain
  • Madrid, Spain, 28046
    • GSK Investigational Site
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • GSK Investigational Site
  • Florida
    • Miramar, Florida, United States, 33025
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Other: placebo; placebo
Experimental: 30mg; active	Drug: ofatumumab; fully human anti-CD20 monoclonal antibody
Experimental: 3mg; active	Drug: ofatumumab; fully human anti-CD20 monoclonal antibody
Experimental: 0.3mg; active	Drug: ofatumumab; fully human anti-CD20 monoclonal antibody
Experimental: 60mg	Drug: ofatumumab; fully human anti-CD20 monoclonal antibody
Experimental: 100mg	Drug: ofatumumab; fully human anti-CD20 monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Kurrasch R, Brown JC, Chu M, Craigen J, Overend P, Patel B, Wolfe S, Chang DJ. Subcutaneously administered ofatumumab in rheumatoid arthritis: a phase I/II study of safety, tolerability, pharmacokinetics, and pharmacodynamics. J Rheumatol. 2013 Jul;40(7):1089-96. doi: 10.3899/jrheum.121118. Epub 2013 Jun 1.

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2008
• Primary Completion (Actual): March 11, 2011
• Study Completion (Actual): May 2, 2011

Study Registration Dates

• First Submitted: May 28, 2008
• First Submitted That Met QC Criteria: May 28, 2008
• First Posted (Estimate): May 30, 2008

Study Record Updates

• Last Update Posted (Actual): June 26, 2017
• Last Update Submitted That Met QC Criteria: June 23, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: B-cell depletion; rheumatoid arthritis,; GSK1841157;; anti-CD20 monoclonal antibody,
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Antineoplastic Agents; Ofatumumab
• Other Study ID Numbers: OFA110867