Last updated: 11/07/2018 18:00:51
Study to evaluate SC route of administration of Ofatumumab in RA patients
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: Clinical phase I/IIA study of subcutaneously administration of Ofatumumab in Rheumatoid Arthritis patients on stable dose Methotrexate
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Single (Participant)
Allocation:
Randomized
Primary outcomes:
Safety and tolerability as described by the incidence and severity of adverse events [AEs], clinical laboratory parameters and vital signs.
Timeframe: throughout the study
Secondary outcomes:
Requirement for the use of pre-medication, including the timing, type and dose required.
Timeframe: 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.
Timeframe: 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.
Timeframe: throughout study
Immunogenicity as measured by the incidence, titre and type of human anti-human antibody (HAHA) immune response.
Timeframe: 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,
Timeframe: 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),
Timeframe: throughout study
serum amyloid A (SAA), CD-3+, CD-4+ and CD-8+ lymphocytes or other biomarkers, as data permit.
Timeframe: 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
Timeframe: throughout study
Interventions:
Other: placebo
Drug: ofatumumab
Enrollment:
35
Observational study model:
Not applicable
Primary completion date:
2011-11-03
Time perspective:
Not applicable
Clinical publications:
Regina Kurrasch, Judith C Brown, Myron Chu, Jenny Craigen, Philip Overend, Bela Patel, Steven Wolfe, David J Chang. Subcutaneously Administered Ofatumumab in Rheumatoid Arthritis: A Phase I/II Study of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics. J Rheumatol. 2013;40(7):1089-1096 .
Medical condition
Arthritis, Rheumatoid
Product
ofatumumab
Collaborators
Not applicable
Study date(s)
June 2008 to May 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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 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)
Inclusion and exclusion criteria
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
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)
Trial location(s)
Location
GSK Investigational Site
Miramar, Florida, United States, 33025
Status
Study Complete
Location
GSK Investigational Site
Adelaide, South Australia, Australia, 5000
Status
Study Complete
Location
GSK Investigational Site
Anniston, Alabama, United States, 36207
Status
Study Complete
Location
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
2011-11-03
Actual study completion date
2011-02-05
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study OFA110867 can be found on the GSK Clinical Study Register.
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