Arthritis, RheumatoidPhase 1NCT00686868
Study to Evaluate SC Route of Administration of Ofatumumab in RA Patients
A Phase 1 study testing ofatumumab in people with Arthritis, Rheumatoid, run by GlaxoSmithKline at 17 sites in 9 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arthritis, Rheumatoid
- What is being tested?
- ofatumumab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 17 sitesin 9 countries
- Study dates
- 13 Jun 2008to 2 May 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 22Show fewer
- 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 locations and contacts
17 sites in 9 countries.
17 sites in 9 countries
Australia4 sites
GSK Investigational Site
Adelaide, South Australia, 5000
GSK Investigational Site
Heidelberg, Victoria, 3084
GSK Investigational Site
Melbourne, Victoria, 3004
GSK Investigational Site
Randwick, New South Wales, 2031
Russia4 sites
GSK Investigational Site
Moscow, 115522
GSK Investigational Site
Ryazan, 390026
GSK Investigational Site
Smolensk, 214018
GSK Investigational Site
Yaroslavl, 150003
United States2 sites
GSK Investigational Site
Anniston, Alabama, 36207
GSK Investigational Site
Miramar, Florida, 33025
Belgium2 sites
GSK Investigational Site
Brussels, 1200
GSK Investigational Site
Leuven, 3000
About this study
Official title: Clinical Phase I/IIA Study of Subcutaneously Administration of Ofatumumab in Rheumatoid Arthritis Patients on Stable Dose Methotrexate
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
- Being tested
- placebo, ofatumumab
- Keywords
- GSK1841157;, rheumatoid arthritis,, B-cell depletion, anti-CD20 monoclonal antibody,
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placeboOther
placebo
ofatumumabDrug
fully human anti-CD20 monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| 30mg | Experimental | active Receives: Drug: ofatumumab |
| 3mg | Experimental | active Receives: Drug: ofatumumab |
| 0.3mg | Experimental | active Receives: Drug: ofatumumab |
| placebo | Placebo comparator | placebo Receives: Other: placebo |
| 60mg | Experimental | 60mg Receives: Drug: ofatumumab |
| 100mg | Experimental | 100mg Receives: Drug: ofatumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability as described by the incidence and severity of adverse events [AEs], clinical laboratory parameters and vital signs.
Measured: throughout the study
Secondary outcomes (8)
Requirement for the use of pre-medication, including the timing, type and dose required.
Measured: 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.
Measured: 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.
Measured: throughout study
Immunogenicity as measured by the incidence, titre and type of human anti-human antibody (HAHA) immune response.
Measured: 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,
Measured: 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),
Measured: throughout study
serum amyloid A (SAA), CD-3+, CD-4+ and CD-8+ lymphocytes or other biomarkers, as data permit.
Measured: 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
Measured: throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2008 (estimated)
- Study start13 Jun 2008
- Primary completion11 Mar 2011
- Study completion2 May 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Arthritis, RheumatoidStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00686868
- Sponsor's protocol ID
- OFA110867
- Status last verified
- Jun 2017
- First submitted
- 28 May 2008
- Last updated
- 26 Jun 2017
- Results posted
- No
Publications
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.
PubMed 23729801
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Phase I/IIA Study of Subcutaneously Administration of Ofatumumab in Rheumatoid Arthritis Patients on Stable Dose Methotrexate
- ClinicalTrials.gov ID
- NCT00686868
- Acronym / sponsor ID
- OFA110867
- Conditions
- Arthritis, Rheumatoid
- Keywords
- GSK1841157;, rheumatoid arthritis,, B-cell depletion, anti-CD20 monoclonal antibody,
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 13 Jun 2008 (actual)
- Primary completion
- 11 Mar 2011 (actual)
- Study completion
- 2 May 2011 (actual)
- First posted
- 30 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 30mg | Experimental | Drug: ofatumumabactive |
| 3mg | Experimental | Drug: ofatumumabactive |
| 0.3mg | Experimental | Drug: ofatumumabactive |
| placebo | Placebo comparator | Other: placeboplacebo |
| 60mg | Experimental | Drug: ofatumumab60mg |
| 100mg | Experimental | Drug: ofatumumab100mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (22 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| placeboplacebo | Other | placebo |
| ofatumumabfully human anti-CD20 monoclonal antibody | Drug | 0.3mg, 100mg, 30mg, 3mg, 60mg |
Primary outcome
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
8 secondary outcomes
Requirement for the use of pre-medication, including the timing, type and dose required.
Time frame: 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.
Time frame: 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.
Time frame: throughout study
Immunogenicity as measured by the incidence, titre and type of human anti-human antibody (HAHA) immune response.
Time frame: 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,
Time frame: 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),
Time frame: throughout study
serum amyloid A (SAA), CD-3+, CD-4+ and CD-8+ lymphocytes or other biomarkers, as data permit.
Time frame: 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
Time frame: throughout study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2017.
- Derived from this study: PubMed 23729801Kurrasch 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 for study OFA110867 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
Related trials for Arthritis, Rheumatoid
RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
Sjogren's Syndrome, Sjögren
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
17 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ofatumumab in people with Arthritis, Rheumatoid, run by GlaxoSmithKline at 17 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Australia, Russia, United States, Belgium, France and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00686868, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2017.