Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis
Brief summary
The purpose of the study is to evaluate the effectiveness of four dosing regimens of fostamatinib compared to placebo, in patients with rheumatoid arthritis (RA) who are taking methotrexate but not responding. The study will last for 12 weeks.
Detailed description
(OSKIRA-Asia-1): A Multi-centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Dose Ranging Study in Asia Evaluating Efficacy and Safety of Fostamatinib in Patients with Active Rheumatoid Arthritis who are Inadequate Responders to Methotrexate Therapy
Interventions
DRUGFostamatinib
Fostamatinib 100mg twice daily for 12 weeks
DRUGPlacebo
Placebo twice daily for 12 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female aged 18 and over * Active rheumatoid arthritis (RA) diagnosed after the age of 16 * 6 or more swollen joints and 6 or more tender/painful joints from certain joints in the hands, wrists, arms and knees * At least one of: positive result for rheumatoid factor test, either in the past or currently (blood test); x-ray showing bone erosion within the last 12 months; presence of certain antibodies in the blood (blood test) * Currently taking methotrexate for at least 4 months (and on a stable dose for at least 6 weeks)
Exclusion criteria
* Females who are pregnant or breast feeding * Certain inflammatory conditions (other than rheumatoid arthritis), connective tissue diseases or chronic pain disorders. * Previously taken, but not responded to, certain biological treatments for rheumatoid arthritis * High blood pressure that is not controlled by medication * Low levels of neutrophils in the blood (blood test).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Achieving ACR20 at Week 12, Comparison Between Fostamatinib and Placebo | 12 weeks | ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Achieving ACR50 at Week 12, Comparison Between Fostamatinib and Placebo | 12 weeks | ACR50: American College of Rheumatology 50% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day. |
| Proportion of Patients Achieving ACR70 at Week 12, Comparison Between Fostamatinib and Placebo | 12 weeks | ACR70: American College of Rheumatology 70% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day. |
| ACRn - Comparison Between Fostamatinib and Placebo at Week 12 | Baseline and 12 weeks | ACRn: American College of Rheumatology index of RA improvement, based on smallest percentage improvement in the count of swollen joints (out of 28 joints), count of tender joints (out of 28 joints), or in blood test measures of inflammation (such as C-Reactive Protein) or the physician or patient's own assessments of disease activity, pain and physical function. Scores are reported as a percentage improvement on a scale of -100 to +100, with larger values representing a better clinical outcome. Mean refers to change at Week 12. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day. |
| Proportion of Patients Achieving DAS28-CRP<=3.2 at Week 12, Comparison Between Fostamatinib and Placebo | 12 weeks | DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. DAS28-CRP score of \<=3.2 indicates low disease activity. BID = twice daily, CRP = C-reactive protein, , DMARD = disease modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once daily. |
| Proportion of Patients Achieving ACR20 at Week 1, Comparison Between Fostamatinib and Placebo | 1 week | ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally. |
| Proportion of Patients With HAQ-DI Response at Week 12, Comparison Between Fostamatinib and Placebo | 12 weeks | HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygiene, reach, grip and common daily activities) and dividing by the number of categories completed. The HAQ-DI score takes values between 0 and 3, with higher score indicating greater disability. HAQ-DI response is a reduction from baseline in HAQ-DI greater than or equal to the minimally important difference (0.22). BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day. |
| SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 12 | Baseline and 12 weeks | SF-36 = 36-item Short Form Health Survey, as a measure of health related quality of life. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional and Mental Health) are derived and normalised to a scale of 0 to 100. The physical and mental component scores (PCS and MCS) are derived by multiplying each of these 8 scores by a constant, summing them and standardising against a population with mean of 50, standard deviation of 10. A higher score represents better quality of life. Mean changes from baseline are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Mean refers to change in scores at Week 12. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day. |
| SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 12 | Baseline and 12 weeks | SF-36 = 36-item Short Form Health Survey, as a measure of health related quality of life. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional and Mental Health) are derived and normalised to a scale of 0 to 100. The physical and mental component scores (PCS and MCS) are derived by multiplying each of these 8 scores by a constant, summing them and standardising against a population with mean of 50, standard deviation of 10. A higher score represents better quality of life. Mean changes from baseline are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Mean refers to change in scores at Week 12. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day. |
| Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | 12 weeks | Change from baseline in DAS28-CRP at Week 12 was derived and categorised using the European League Against Rheumatism (EULAR) response criteria. BID = twice a day, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day. |
Countries
Hong Kong, Japan, South Korea, Taiwan, Thailand, Vietnam
Participant flow
Recruitment details
A total of 298 patients were enrolled: 31, 33, 33, 33 & 33 were randomised to Groups A, B, C, D & E respectively (all received at least 1 dose of investigational product).
Pre-assignment details
A total of 135 patients failed screening.
Participants by arm
| Arm | Count |
|---|---|
| FOSTA 100 MG BID PO Dosing Group A | 31 |
| FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO Dosing Group B | 33 |
| FOSTA 75 MG BID PO Dosing Group C | 33 |
| FOSTA 50 MG BID PO Dosing Group D | 33 |
| PLACEBO PO Dosing Group E | 33 |
| Total | 163 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 3 | 0 | 0 |
| Overall Study | eg change in circumstances | 0 | 2 | 0 | 1 | 1 |
| Overall Study | Severe non-compliance to protocol | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Study-specific discontinuation criteria | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Study stopped | 6 | 6 | 8 | 7 | 7 |
Baseline characteristics
| Characteristic | FOSTA 100 MG BID PO | FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO | FOSTA 75 MG BID PO | FOSTA 50 MG BID PO | PLACEBO PO | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 51 years STANDARD_DEVIATION 14.3 | 55 years STANDARD_DEVIATION 10.4 | 56 years STANDARD_DEVIATION 11.5 | 50 years STANDARD_DEVIATION 11.4 | 53 years STANDARD_DEVIATION 11.3 | 53 years STANDARD_DEVIATION 11.9 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 31 Participants | 33 Participants | 33 Participants | 33 Participants | 33 Participants | 163 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Indian or Pakistani | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 31 Participants | 25 Participants | 27 Participants | 31 Participants | 28 Participants | 142 Participants |
| Sex: Female, Male Male | 0 Participants | 8 Participants | 6 Participants | 2 Participants | 5 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 21 / 31 | 17 / 33 | 17 / 33 | 16 / 33 | 15 / 33 |
| serious Total, serious adverse events | 1 / 31 | 1 / 33 | 3 / 33 | 0 / 33 | 1 / 33 |
Outcome results
Primary
Proportion of Patients Achieving ACR20 at Week 12, Comparison Between Fostamatinib and Placebo
ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
Time frame: 12 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOSTA 100 MG BID PO | Proportion of Patients Achieving ACR20 at Week 12, Comparison Between Fostamatinib and Placebo | 53.8 Percentage of responders |
| FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO | Proportion of Patients Achieving ACR20 at Week 12, Comparison Between Fostamatinib and Placebo | 55.2 Percentage of responders |
| FOSTA 75 MG BID PO | Proportion of Patients Achieving ACR20 at Week 12, Comparison Between Fostamatinib and Placebo | 25.9 Percentage of responders |
| FOSTA 50 MG BID PO | Proportion of Patients Achieving ACR20 at Week 12, Comparison Between Fostamatinib and Placebo | 46.4 Percentage of responders |
| PLACEBO PO | Proportion of Patients Achieving ACR20 at Week 12, Comparison Between Fostamatinib and Placebo | 32.1 Percentage of responders |
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.05980% CI: [0.07, 0.39]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.05480% CI: [0.08, 0.39]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.5780% CI: [-0.2, 0.08]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.26280% CI: [-0.02, 0.29]Mantel Haenszel
Secondary
ACRn - Comparison Between Fostamatinib and Placebo at Week 12
ACRn: American College of Rheumatology index of RA improvement, based on smallest percentage improvement in the count of swollen joints (out of 28 joints), count of tender joints (out of 28 joints), or in blood test measures of inflammation (such as C-Reactive Protein) or the physician or patient's own assessments of disease activity, pain and physical function. Scores are reported as a percentage improvement on a scale of -100 to +100, with larger values representing a better clinical outcome. Mean refers to change at Week 12. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
Time frame: Baseline and 12 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FOSTA 100 MG BID PO | ACRn - Comparison Between Fostamatinib and Placebo at Week 12 | 25.52 Percentage improvement from baseline | Standard Deviation 37.029 |
| FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO | ACRn - Comparison Between Fostamatinib and Placebo at Week 12 | 24.18 Percentage improvement from baseline | Standard Deviation 39.925 |
| FOSTA 75 MG BID PO | ACRn - Comparison Between Fostamatinib and Placebo at Week 12 | 3.59 Percentage improvement from baseline | Standard Deviation 29.774 |
| FOSTA 50 MG BID PO | ACRn - Comparison Between Fostamatinib and Placebo at Week 12 | 15.88 Percentage improvement from baseline | Standard Deviation 24.354 |
| PLACEBO PO | ACRn - Comparison Between Fostamatinib and Placebo at Week 12 | 10.94 Percentage improvement from baseline | Standard Deviation 28.302 |
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.073Van Elteren
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.065Van Elteren
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.317Van Elteren
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.263Van Elteren
Secondary
Proportion of Patients Achieving ACR20 at Week 1, Comparison Between Fostamatinib and Placebo
ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally.
Time frame: 1 week
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. The fostamatinib 100 mg BID combined group contains 31 patients from Dosing Group A and 33 patients from Dosing Group B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOSTA 100 MG BID PO | Proportion of Patients Achieving ACR20 at Week 1, Comparison Between Fostamatinib and Placebo | 21.2 Percentage of responders |
| FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO | Proportion of Patients Achieving ACR20 at Week 1, Comparison Between Fostamatinib and Placebo | 18.2 Percentage of responders |
| FOSTA 75 MG BID PO | Proportion of Patients Achieving ACR20 at Week 1, Comparison Between Fostamatinib and Placebo | 15.2 Percentage of responders |
| FOSTA 50 MG BID PO | Proportion of Patients Achieving ACR20 at Week 1, Comparison Between Fostamatinib and Placebo | 25.0 Percentage of responders |
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.17280% CI: [0.01, 0.21]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.48980% CI: [-0.05, 0.18]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.70480% CI: [-0.08, 0.15]Mantel Haenszel
Secondary
Proportion of Patients Achieving ACR50 at Week 12, Comparison Between Fostamatinib and Placebo
ACR50: American College of Rheumatology 50% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
Time frame: 12 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOSTA 100 MG BID PO | Proportion of Patients Achieving ACR50 at Week 12, Comparison Between Fostamatinib and Placebo | 30.8 Percentage of responders |
| FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO | Proportion of Patients Achieving ACR50 at Week 12, Comparison Between Fostamatinib and Placebo | 34.5 Percentage of responders |
| FOSTA 75 MG BID PO | Proportion of Patients Achieving ACR50 at Week 12, Comparison Between Fostamatinib and Placebo | 7.4 Percentage of responders |
| FOSTA 50 MG BID PO | Proportion of Patients Achieving ACR50 at Week 12, Comparison Between Fostamatinib and Placebo | 10.7 Percentage of responders |
| PLACEBO PO | Proportion of Patients Achieving ACR50 at Week 12, Comparison Between Fostamatinib and Placebo | 14.3 Percentage of responders |
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.11480% CI: [0.03, 0.31]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.03580% CI: [0.08, 0.34]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.33480% CI: [-0.17, 0.02]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.64580% CI: [-0.13, 0.06]Mantel Haenszel
Secondary
Proportion of Patients Achieving ACR70 at Week 12, Comparison Between Fostamatinib and Placebo
ACR70: American College of Rheumatology 70% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
Time frame: 12 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOSTA 100 MG BID PO | Proportion of Patients Achieving ACR70 at Week 12, Comparison Between Fostamatinib and Placebo | 11.5 Percentage of responders |
| FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO | Proportion of Patients Achieving ACR70 at Week 12, Comparison Between Fostamatinib and Placebo | 13.8 Percentage of responders |
| FOSTA 75 MG BID PO | Proportion of Patients Achieving ACR70 at Week 12, Comparison Between Fostamatinib and Placebo | 0 Percentage of responders |
| FOSTA 50 MG BID PO | Proportion of Patients Achieving ACR70 at Week 12, Comparison Between Fostamatinib and Placebo | 0 Percentage of responders |
| PLACEBO PO | Proportion of Patients Achieving ACR70 at Week 12, Comparison Between Fostamatinib and Placebo | 0 Percentage of responders |
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.02880% CI: [0.05, 0.19]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.02180% CI: [0.06, 0.22]Mantel Haenszel
Secondary
Proportion of Patients Achieving DAS28-CRP<=3.2 at Week 12, Comparison Between Fostamatinib and Placebo
DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. DAS28-CRP score of \<=3.2 indicates low disease activity. BID = twice daily, CRP = C-reactive protein, , DMARD = disease modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once daily.
Time frame: 12 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| FOSTA 100 MG BID PO | Proportion of Patients Achieving DAS28-CRP<=3.2 at Week 12, Comparison Between Fostamatinib and Placebo | 34.6 Percentage of responders | 0.81 |
| FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO | Proportion of Patients Achieving DAS28-CRP<=3.2 at Week 12, Comparison Between Fostamatinib and Placebo | 34.5 Percentage of responders | 0.82 |
| FOSTA 75 MG BID PO | Proportion of Patients Achieving DAS28-CRP<=3.2 at Week 12, Comparison Between Fostamatinib and Placebo | 22.2 Percentage of responders | 0.77 |
| FOSTA 50 MG BID PO | Proportion of Patients Achieving DAS28-CRP<=3.2 at Week 12, Comparison Between Fostamatinib and Placebo | 17.9 Percentage of responders | 0.75 |
| PLACEBO PO | Proportion of Patients Achieving DAS28-CRP<=3.2 at Week 12, Comparison Between Fostamatinib and Placebo | 10.7 Percentage of responders | — |
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation appliedp-value: 0.03380% CI: [1.94, 14.31]Regression, Logistic
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.03380% CI: [1.92, 13.61]Regression, Logistic
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.25780% CI: [0.89, 6.89]Regression, Logistic
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.48180% CI: [0.63, 5.04]Regression, Logistic
Secondary
Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo
Change from baseline in DAS28-CRP at Week 12 was derived and categorised using the European League Against Rheumatism (EULAR) response criteria. BID = twice a day, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day.
Time frame: 12 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| FOSTA 100 MG BID PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | No response | 30.8 Percentage of responders | 1.46 |
| FOSTA 100 MG BID PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | Good response | 34.6 Percentage of responders | — |
| FOSTA 100 MG BID PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | Moderate response | 34.6 Percentage of responders | — |
| FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | Moderate response | 24.1 Percentage of responders | — |
| FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | No response | 41.4 Percentage of responders | 1.34 |
| FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | Good response | 34.5 Percentage of responders | — |
| FOSTA 75 MG BID PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | Moderate response | 29.6 Percentage of responders | — |
| FOSTA 75 MG BID PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | No response | 48.1 Percentage of responders | 1.3 |
| FOSTA 75 MG BID PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | Good response | 22.2 Percentage of responders | — |
| FOSTA 50 MG BID PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | No response | 17.9 Percentage of responders | 1.58 |
| FOSTA 50 MG BID PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | Good response | 17.9 Percentage of responders | — |
| FOSTA 50 MG BID PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | Moderate response | 64.3 Percentage of responders | — |
| PLACEBO PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | Moderate response | 53.6 Percentage of responders | — |
| PLACEBO PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | No response | 35.7 Percentage of responders | — |
| PLACEBO PO | Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo | Good response | 10.7 Percentage of responders | — |
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.13180% CI: [1.12, 4.2]Proportional odds model
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.42380% CI: [0.79, 2.82]Proportional odds model
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.78180% CI: [0.45, 1.67]Proportional odds model
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.23980% CI: [0.95, 3.44]Proportional odds model
Secondary
Proportion of Patients With HAQ-DI Response at Week 12, Comparison Between Fostamatinib and Placebo
HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygiene, reach, grip and common daily activities) and dividing by the number of categories completed. The HAQ-DI score takes values between 0 and 3, with higher score indicating greater disability. HAQ-DI response is a reduction from baseline in HAQ-DI greater than or equal to the minimally important difference (0.22). BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day.
Time frame: 12 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOSTA 100 MG BID PO | Proportion of Patients With HAQ-DI Response at Week 12, Comparison Between Fostamatinib and Placebo | 69.2 Percentage of responders |
| FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO | Proportion of Patients With HAQ-DI Response at Week 12, Comparison Between Fostamatinib and Placebo | 48.3 Percentage of responders |
| FOSTA 75 MG BID PO | Proportion of Patients With HAQ-DI Response at Week 12, Comparison Between Fostamatinib and Placebo | 44.4 Percentage of responders |
| FOSTA 50 MG BID PO | Proportion of Patients With HAQ-DI Response at Week 12, Comparison Between Fostamatinib and Placebo | 46.4 Percentage of responders |
| PLACEBO PO | Proportion of Patients With HAQ-DI Response at Week 12, Comparison Between Fostamatinib and Placebo | 50.0 Percentage of responders |
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.16980% CI: [1.06, 4.67]Regression, Logistic
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.83380% CI: [0.45, 1.78]Regression, Logistic
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.61480% CI: [0.37, 1.54]Regression, Logistic
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.74880% CI: [0.42, 1.69]Regression, Logistic
Secondary
SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 12
SF-36 = 36-item Short Form Health Survey, as a measure of health related quality of life. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional and Mental Health) are derived and normalised to a scale of 0 to 100. The physical and mental component scores (PCS and MCS) are derived by multiplying each of these 8 scores by a constant, summing them and standardising against a population with mean of 50, standard deviation of 10. A higher score represents better quality of life. Mean changes from baseline are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Mean refers to change in scores at Week 12. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
Time frame: Baseline and 12 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FOSTA 100 MG BID PO | SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 12 | 7 Units on a scale | Standard Deviation 8.7 |
| FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO | SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 12 | 6 Units on a scale | Standard Deviation 7.7 |
| FOSTA 75 MG BID PO | SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 12 | 2 Units on a scale | Standard Deviation 7 |
| FOSTA 50 MG BID PO | SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 12 | 5 Units on a scale | Standard Deviation 8.9 |
| PLACEBO PO | SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 12 | 4 Units on a scale | Standard Deviation 7.9 |
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.13980% CI: [0.42, 5.82]ANCOVA
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.22380% CI: [-0.13, 5.07]ANCOVA
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.43280% CI: [-4.3, 1.04]ANCOVA
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.48180% CI: [-1.19, 4.09]ANCOVA
Secondary
SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 12
SF-36 = 36-item Short Form Health Survey, as a measure of health related quality of life. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional and Mental Health) are derived and normalised to a scale of 0 to 100. The physical and mental component scores (PCS and MCS) are derived by multiplying each of these 8 scores by a constant, summing them and standardising against a population with mean of 50, standard deviation of 10. A higher score represents better quality of life. Mean changes from baseline are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Mean refers to change in scores at Week 12. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
Time frame: Baseline and 12 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FOSTA 100 MG BID PO | SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 12 | 7 Units on a scale | Standard Deviation 7.5 |
| FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO | SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 12 | 4 Units on a scale | Standard Deviation 7.4 |
| FOSTA 75 MG BID PO | SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 12 | 3 Units on a scale | Standard Deviation 6.8 |
| FOSTA 50 MG BID PO | SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 12 | 5 Units on a scale | Standard Deviation 5.6 |
| PLACEBO PO | SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 12 | 3 Units on a scale | Standard Deviation 5.1 |
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.08780% CI: [0.76, 5.26]ANCOVA
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.88180% CI: [-1.91, 2.41]ANCOVA
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.80680% CI: [-2.64, 1.8]ANCOVA
Comparison: Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or following receipt of any parenteral steroids, or for patients with no post baseline data. Subjects who prematurely withdrew due to project closure have no imputation applied.p-value: 0.54880% CI: [-1.17, 3.23]ANCOVA