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

NCT00686868 | Completed Phase 1

• 1 other identifier: OFA110867
• Study Type: interventional
• Target: 35
• Locations: 9 countries
• Sites: 17

Brief 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.

Conditions

Arthritis, Rheumatoid

Keywords

GSK1841157;; rheumatoid arthritis,; B-cell depletion; anti-CD20 monoclonal antibody,

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability as described by the incidence and severity of adverse events [AEs], clinical laboratory parameters and vital signs.

  throughout the study

Secondary Outcomes (8)

• 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

Study Arms (6)

30mg

EXPERIMENTAL

active

Drug: ofatumumab

3mg

EXPERIMENTAL

active

Drug: ofatumumab

0.3mg

EXPERIMENTAL

active

Drug: ofatumumab

placebo

PLACEBO COMPARATOR

placebo

Other: placebo

60mg

EXPERIMENTAL

60mg

Drug: ofatumumab

100mg

EXPERIMENTAL

100mg

Drug: ofatumumab

Interventions

placebo OTHER

placebo

placebo

ofatumumab DRUG

fully human anti-CD20 monoclonal antibody

0.3mg; 100mg; 30mg; 3mg; 60mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (17)

GSK Investigational Site

Anniston, Alabama, 36207, United States

Location

GSK Investigational Site

Miramar, Florida, 33025, United States

Location

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

GSK Investigational Site

Adelaide, South Australia, 5000, Australia

Location

GSK Investigational Site

Heidelberg, Victoria, 3084, Australia

Location

GSK Investigational Site

Melbourne, Victoria, 3004, Australia

Location

GSK Investigational Site

Brussels, 1200, Belgium

Location

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Échirolles, 38130, France

Location

GSK Investigational Site

Verona, Veneto, 37126, Italy

Location

GSK Investigational Site

Christchurch, 8011, New Zealand

Location

GSK Investigational Site

Bydgoszcz, 85168, Poland

Location

GSK Investigational Site

Moscow, 115522, Russia

Location

GSK Investigational Site

Ryazan, 390026, Russia

Location

GSK Investigational Site

Smolensk, 214018, Russia

Location

GSK Investigational Site

Yaroslavl, 150003, Russia

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

Related Publications (1)

• 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.

  PMID: 23729801 DERIVED

Related Links

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

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

ofatumumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2008
• First Posted: May 30, 2008
• Study Start: June 13, 2008
• Primary Completion: March 11, 2011
• Study Completion: May 2, 2011
• Last Updated: June 26, 2017

Record last verified: 2017-06

Locations

BE (2); NZ (1); ES (1); PL (1); US (2); RU (4); AU (4); IT (1); FR (1)