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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00686868
First received: May 28, 2008
Last updated: November 7, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Arthritis, Rheumatoid
Other: placebo
Drug: ofatumumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Clinical Phase I/IIA Study of Subcutaneously Administration of Ofatumumab in Rheumatoid Arthritis Patients on Stable Dose Methotrexate

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Requirement for the use of pre-medication, including the timing, type and dose required. [ Time Frame: throughout study ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Immunogenicity as measured by the incidence, titre and type of human anti-human antibody (HAHA) immune response. [ Time Frame: throughout study ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • serum amyloid A (SAA), CD-3+, CD-4+ and CD-8+ lymphocytes or other biomarkers, as data permit. [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: June 2008
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Placebo Comparator: placebo
placebo
Other: placebo
placebo
Other Name: placebo
Experimental: 60mg
60mg
Drug: ofatumumab
fully human anti-CD20 monoclonal antibody
Experimental: 100mg
100mg
Drug: ofatumumab
fully human anti-CD20 monoclonal antibody

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00686868

Locations
United States, Alabama
GSK Investigational Site
Anniston, Alabama, United States, 36207
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00686868     History of Changes
Other Study ID Numbers: OFA110867
Study First Received: May 28, 2008
Last Updated: November 7, 2013
Health Authority: United States: Food and Drug Administration
Australia: Therapeutic Goods Administration

Keywords provided by GlaxoSmithKline:
GSK1841157;
rheumatoid arthritis,
B-cell depletion
anti-CD20 monoclonal antibody,

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 19, 2014