Rheumatoid ArthritisPhase 2OSKIRA 4 SSNCT02092961
Randomised Double-Blind, Placebo-Controlled, Parallel Group Study in Patients With Active Rheumatoid Arthritis:Magnetic Resonance Imaging Sub-Study
A Phase 2 study testing Fostamatinib and Adalimumab in people with Rheumatoid Arthritis, run by AstraZeneca at 21 sites in 11 countries.
Trial summary
This is a sub-study of the OSKIRA-4 study, (D4300C0004, NCT01264770) to explore alternative and more sensitive modalities for measuring the beneficial effects of syk inhibition with fostamatinib in patients with active RA. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Fostamatinib and Adalimumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 198 participants
- Where
- 21 sitesin 11 countries
- Study dates
- Feb 2011to Jul 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 and over
- Active rheumatoid arthritis (RA) diagnosed after the age of 16
- Diagnosis within 5 years prior to study visit 1 and inadequate response to treatment with a maximum 2 Disease-Modifying anti-rheumatic drug (DMARD) therapies, or
- diagnosis within 5 years prior to study visit 1 and intolerance to DMARD therapy, or
- diagnosis within 2 years prior to study visit 1 and no previous use of DMARDs
- 4 or more swollen joints and 4 or more tender/painful joints (from 28 joint count)
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- Either Erythrocyte Sedimentation Rate (ESR) blood result of 28mm/h or more, or
- C-Reactive Protein (CRP) blood result of 10mg/L or more
- At least 2 of the following:
- documented history or current presence of positive rheumatoid factor (blood test),
- radiographic erosion within 12 months prior to study enrolment,
- presence of serum anti-cyclic citrullinated peptide antibodies (blood test)
- Presence of at least one swollen hand or wrist joint.
- Presence of synovitis on baseline MRI scan, defined as at least 1 joint with RAMRIS synovitis score of +1 or greater.
Who cannot join
- Females who are pregnant or breast feeding
- Poorly controlled hypertension
- Liver disease or significant liver function test abnormalities
- Certain inflammatory conditions (other than rheumatoid arthritis), connective tissue diseases or chronic pain disorders
- Recent or significant cardiovascular disease
- Significant active or recent infection including tuberculosis
Show all 15Show fewer
- Previously received treatment with a TNF alpha antagonist (including etanercept, certolizumab, adalimumab, infliximab, golimumab) or anakinra or previous treatment with other biological agent including rituximab, abatacept and tocilizumab
- Use of any DMARDs within 6 weeks before first study visit
- Severe renal impairment
- Neutropenia
- Unable to undergo an MRI examination (e.g. presence of a pacemaker, defibrillator, or other implanted metallic device such as anterior interbody cages, aneurysm clip or pedicle screws)
- Known allergy to Gadolinium-based contrast agent,
- Tattoos [in area of examination if contains metallic pigment]
- Likely to require sedation for the procedure
- eGFR less than 55 mL/min
Trial locations and contacts
21 sites in 11 countries.
21 sites in 11 countries
United States6 sites
Research Site
Austin, Texas
Research Site
Brooklyn, New York
Research Site
Glendale, Arizona
Research Site
Jackson, Tennessee
Research Site
Paradise Valley, Arizona
Research Site
Phoenix, Arizona
South Africa3 sites
Research Site
Durban
Research Site
Pretoria
Research Site
Stellenbosch
About this study
Official title: A Phase IIB, Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Fostamatinib Disodium Monotherapy Compared With Placebo or Adalimumab Monotherapy in Patients With Active Rheumatoid Arthritis: Magnetic Resonance Imaging Sub-Study
This is a sub-study of the OSKIRA-4 study, (D4300C0004, NCT01264770) to explore alternative and more sensitive modalities for measuring the beneficial effects of syk inhibition with fostamatinib in patients with active RA. This MRI sub-study was reported later than the main study due to recruitment delays at specialist imaging sites and so is registered and presented entirely separately to the main study results.
This study will investigate the impact of treatment on joint activity and damage by assessing synovitis, osteitis, bone erosions and joint space narrowing.
Read the detailed description
Sub-study to OSKIRA-4: A Phase IIB, Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Fostamatinib Disodium Monotherapy Compared with Placebo or Adalimumab Monotherapy in Patients with Active Rheumatoid Arthritis: Magnetic Resonance Imaging Sub-Study Date: 21 March 2011 Version: 1 Primary objective: Assess the efficacy of fostamatinib in reducing joint synovial disease activity as measured by: - Change from baseline to Week 6 (versus placebo) in OMERACT RAMRIS synovitis score.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Fostamatinib, Adalimumab, Placebo of Fostamatinib, Placebo of Adalimumab
- Keywords
- Rheumatoid Arthritis, OSKIRA, fostamatinib, CE-MRI, DCE-MRI
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FostamatinibDrug
Fostamatinib 100mg twice daily.
AdalimumabDrug
Adalimumab 40 mg by subcutaneous injection every 2 weeks for 24 weeks.
Placebo of FostamatinibDrug
Placebo bid for 6 weeks.
Placebo of AdalimumabDrug
Placebo injection once every two weeks.
| Study group | Role | What they receive |
|---|---|---|
| Dosing Group A | Experimental | Oral treatment and subcutaneous injection. Receives: Drug: Fostamatinib; Drug: Placebo of Adalimumab |
| Dosing Group D | Active comparator | Oral treatment and subcutaneous injection. Receives: Drug: Adalimumab; Drug: Placebo of Fostamatinib |
| Dosing Group E | Placebo comparator | Placebo bid for 6 weeks followed by switch to 100 mg fostamatinib bid for 24 weeks, plus placebo subcutaneous injection every 2 weeks. Receives: Drug: Fostamatinib; Drug: Placebo of Fostamatinib; Drug: Placebo of Adalimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
OMERACT RAMRIS Synovitis Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)
OMERACT RAMRIS synovitis score was based on 8 joints, scored from MRI images, and ranged from 0 to 24 with a smaller value indicating a better clinical condition. Median changes from baseline are shown at each visit (defined as post-baseline minus baseline) with negative values indicative of a better clinical condition. BID = twice daily, CI = confidence interval, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, MRI = magnetic resonance imaging, OMERACT = Outcome Measures in Rheumatoid Arthritis Clinical Trials, PO = orally, RAMRIS = Rheumatoid Arthritis Magnetic Resonance Image Scoring system, SC = subcutaneous.
Measured: Baseline, 6 and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2014 (estimated)
- Study startFeb 2011
- Primary completionJul 2013
- Study completionJul 2013
Why it stopped: AZ decision to discontinue fostamatinib development in RA; rights to fostamatinib returned to Rigel Pharmaceuticals.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 198 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Neil MacKillop, MD PhD, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02092961
- Sponsor's protocol ID
- D4300C00004Sub
- Acronym
- OSKIRA 4 SS
- Status last verified
- Apr 2014
- First submitted
- 19 Mar 2014
- Last updated
- 25 Jun 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIB, Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Fostamatinib Disodium Monotherapy Compared With Placebo or Adalimumab Monotherapy in Patients With Active Rheumatoid Arthritis: Magnetic Resonance Imaging Sub-Study
- ClinicalTrials.gov ID
- NCT02092961
- Acronym / sponsor ID
- OSKIRA 4 SS / D4300C00004Sub
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis, OSKIRA, fostamatinib, CE-MRI, DCE-MRI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: AZ decision to discontinue fostamatinib development in RA; rights to fostamatinib returned to Rigel Pharmaceuticals.
- Enrolment
- 198 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Feb 2011
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 20 Mar 2014 (estimated)
- Results
- Posted 25 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a sub-study of the OSKIRA-4 study, (D4300C0004, NCT01264770) to explore alternative and more sensitive modalities for measuring the beneficial effects of syk inhibition with fostamatinib in patients with active RA. This MRI sub-study was reported later than the main study due to recruitment delays at specialist imaging sites and so is registered and presented entirely separately to the main study results.
This study will investigate the impact of treatment on joint activity and damage by assessing synovitis, osteitis, bone erosions and joint space narrowing.
Detailed description
Sub-study to OSKIRA-4: A Phase IIB, Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Fostamatinib Disodium Monotherapy Compared with Placebo or Adalimumab Monotherapy in Patients with Active Rheumatoid Arthritis: Magnetic Resonance Imaging Sub-Study Date: 21 March 2011 Version: 1 Primary objective: Assess the efficacy of fostamatinib in reducing joint synovial disease activity as measured by: - Change from baseline to Week 6 (versus placebo) in OMERACT RAMRIS synovitis score.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dosing Group A | Experimental | Drug: Fostamatinib, Drug: Placebo of AdalimumabOral treatment and subcutaneous injection. |
| Dosing Group D | Active comparator | Drug: Adalimumab, Drug: Placebo of FostamatinibOral treatment and subcutaneous injection. |
| Dosing Group E | Placebo comparator | Drug: Fostamatinib, Drug: Placebo of Fostamatinib, Drug: Placebo of AdalimumabPlacebo bid for 6 weeks followed by switch to 100 mg fostamatinib bid for 24 weeks, plus placebo subcutaneous injection every 2 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Male or female aged 18 and over
- Active rheumatoid arthritis (RA) diagnosed after the age of 16
- Diagnosis within 5 years prior to study visit 1 and inadequate response to treatment with a maximum 2 Disease-Modifying anti-rheumatic drug (DMARD) therapies, or
- diagnosis within 5 years prior to study visit 1 and intolerance to DMARD therapy, or
- diagnosis within 2 years prior to study visit 1 and no previous use of DMARDs
Key exclusion criteria (15 listed)
- Females who are pregnant or breast feeding
- Poorly controlled hypertension
- Liver disease or significant liver function test abnormalities
- Certain inflammatory conditions (other than rheumatoid arthritis), connective tissue diseases or chronic pain disorders
- Recent or significant cardiovascular disease
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 |
|---|---|---|
| FostamatinibFostamatinib 100mg twice daily. | Drug | Dosing Group A, Dosing Group E |
| AdalimumabAdalimumab 40 mg by subcutaneous injection every 2 weeks for 24 weeks. | Drug | Dosing Group D |
| Placebo of FostamatinibPlacebo bid for 6 weeks. | Drug | Dosing Group D, Dosing Group E |
| Placebo of AdalimumabPlacebo injection once every two weeks. | Drug | Dosing Group A, Dosing Group E |
Primary outcome
OMERACT RAMRIS Synovitis Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)
Time frame: Baseline, 6 and 24 weeks
OMERACT RAMRIS synovitis score was based on 8 joints, scored from MRI images, and ranged from 0 to 24 with a smaller value indicating a better clinical condition. Median changes from baseline are shown at each visit (defined as post-baseline minus baseline) with negative values indicative of a better clinical condition. BID = twice daily, CI = confidence interval, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, MRI = magnetic resonance imaging, OMERACT = Outcome Measures in Rheumatoid Arthritis Clinical Trials, PO = orally, RAMRIS = Rheumatoid Arthritis Magnetic Resonance Image Scoring system, SC = subcutaneous.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Neil MacKillop, MD PhD study director
AstraZeneca
21 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fostamatinib and Adalimumab in people with Rheumatoid Arthritis, run by AstraZeneca at 21 sites in 11 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 14 inclusion and 15 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: stopped early, as of the sponsor's last update on 25 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, South Africa, Germany, Hungary, United Kingdom and 6 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
OMERACT RAMRIS Synovitis Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren) (time frame: Baseline, 6 and 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Jun 2014.