Study to Evaluate SC Route of Administration of Ofatumumab in RA Patients
Primary Purpose
Arthritis, Rheumatoid
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
placebo
ofatumumab
Sponsored by
About this trial
This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring GSK1841157;, rheumatoid arthritis,, B-cell depletion, anti-CD20 monoclonal antibody,
Eligibility 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)
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Arm Label
30mg
3mg
0.3mg
placebo
60mg
100mg
Arm Description
active
active
active
placebo
60mg
100mg
Outcomes
Primary Outcome Measures
Safety and tolerability as described by the incidence and severity of adverse events [AEs], clinical laboratory parameters and vital signs.
Secondary Outcome Measures
Requirement for the use of pre-medication, including the timing, type and dose required.
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.
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.
Immunogenicity as measured by the incidence, titre and type of human anti-human antibody (HAHA) immune response.
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,
Immunoglobulins (IgA, IgG, IgM), Complement (CH50, C3, C4), IgM Rheumatoid Factor (IgM-RF), IgA-RF and IgG-RF, anti-cyclic citrullinated peptide antibody (aCCP),
serum amyloid A (SAA), CD-3+, CD-4+ and CD-8+ lymphocytes or other biomarkers, as data permit.
Pharmacodynamics (B-cell depletion and re-population) as measured by CD-19 peripheral blood B- lymphocyte count via routine FACS analysis.Other Secondary Endpoints
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00686868
Brief Title
Study to Evaluate SC Route of Administration of Ofatumumab in RA Patients
Official Title
Clinical Phase I/IIA Study of Subcutaneously Administration of Ofatumumab in Rheumatoid Arthritis Patients on Stable Dose Methotrexate
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
June 13, 2008 (Actual)
Primary Completion Date
March 11, 2011 (Actual)
Study Completion Date
May 2, 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid
Keywords
GSK1841157;, rheumatoid arthritis,, B-cell depletion, anti-CD20 monoclonal antibody,
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
30mg
Arm Type
Experimental
Arm Description
active
Arm Title
3mg
Arm Type
Experimental
Arm Description
active
Arm Title
0.3mg
Arm Type
Experimental
Arm Description
active
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
placebo
Arm Title
60mg
Arm Type
Experimental
Arm Description
60mg
Arm Title
100mg
Arm Type
Experimental
Arm Description
100mg
Intervention Type
Other
Intervention Name(s)
placebo
Intervention Description
placebo
Intervention Type
Drug
Intervention Name(s)
ofatumumab
Intervention Description
fully human anti-CD20 monoclonal antibody
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Requirement for the use of pre-medication, including the timing, type and dose required.
Time Frame
throughout study
Title
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
Title
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
Title
Immunogenicity as measured by the incidence, titre and type of human anti-human antibody (HAHA) immune response.
Time Frame
throughout study
Title
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
Title
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
Title
serum amyloid A (SAA), CD-3+, CD-4+ and CD-8+ lymphocytes or other biomarkers, as data permit.
Time Frame
throughout study
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
Facility Name
GSK Investigational Site
City
Miramar
State/Province
Florida
ZIP/Postal Code
33025
Country
United States
Facility Name
GSK Investigational Site
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
GSK Investigational Site
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
GSK Investigational Site
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
GSK Investigational Site
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
GSK Investigational Site
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Facility Name
GSK Investigational Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
GSK Investigational Site
City
Echirolles
ZIP/Postal Code
38130
Country
France
Facility Name
GSK Investigational Site
City
Verona
State/Province
Veneto
ZIP/Postal Code
37126
Country
Italy
Facility Name
GSK Investigational Site
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
Facility Name
GSK Investigational Site
City
Bydgoszcz
ZIP/Postal Code
85168
Country
Poland
Facility Name
GSK Investigational Site
City
Moscow
ZIP/Postal Code
115522
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Ryazan
ZIP/Postal Code
390026
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Smolensk
ZIP/Postal Code
214018
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Yaroslavl
ZIP/Postal Code
150003
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
23729801
Citation
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.
Results Reference
derived
Learn more about this trial
Study to Evaluate SC Route of Administration of Ofatumumab in RA Patients
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