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

Arthritis, Rheumatoid Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00686868
• Other study ID #: OFA110867
• Status: Completed
• Phase: Phase 1
• First received: May 28, 2008
• Last updated: June 23, 2017
• Start date: June 13, 2008
• Est. completion date: May 2, 2011

Study information

• Verified date: June 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: May 2, 2011
• Est. primary completion date: March 11, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Other:
• placebo
placebo

Drug:
• ofatumumab
fully human anti-CD20 monoclonal antibody

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Adelaide	South Australia
Australia	GSK Investigational Site	Heidelberg	Victoria
Australia	GSK Investigational Site	Melbourne	Victoria
Australia	GSK Investigational Site	Randwick	New South Wales
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Leuven
France	GSK Investigational Site	Echirolles
Italy	GSK Investigational Site	Verona	Veneto
New Zealand	GSK Investigational Site	Christchurch
Poland	GSK Investigational Site	Bydgoszcz
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Ryazan
Russian Federation	GSK Investigational Site	Smolensk
Russian Federation	GSK Investigational Site	Yaroslavl
Spain	GSK Investigational Site	Madrid
United States	GSK Investigational Site	Anniston	Alabama
United States	GSK Investigational Site	Miramar	Florida

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Italy,  New Zealand,  Poland,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability as described by the incidence and severity of adverse events [AEs], clinical laboratory parameters and vital signs.		throughout the study
Secondary	Requirement for the use of pre-medication, including the timing, type and dose required.		throughout study
Secondary	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
Secondary	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
Secondary	Immunogenicity as measured by the incidence, titre and type of human anti-human antibody (HAHA) immune response.		throughout study
Secondary	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
Secondary	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
Secondary	serum amyloid A (SAA), CD-3+, CD-4+ and CD-8+ lymphocytes or other biomarkers, as data permit.		throughout study
Secondary	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

External Links

•   Results for study OFA110867 can be found on the GSK Clinical Study Register.