Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, OSKIRA, Fostamatinib
Brief summary
The purpose of this study is to evaluate the long term safety and tolerability of fostamatinib in patients with rheumatoid arthritis (RA).
Interventions
DRUGFostamatinib
Fostamatinib 100mg twice daily
Sponsors
AstraZeneca
Study design
Allocation
NON_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
* Patients who have successfully completed a qualifying study (D4300C00001, D4300C00002, D4300C00003 or D4300C00004) with fostamatinib * Patients who have participated in a qualifying study and who have been classified as non-responders due to pre-defined lack of efficacy at Week 12 (D4300C00001, D4300C00002, D4300C00003).
Exclusion criteria
* Premature withdrawal from the qualifying study (D4300C00001, D4300C00002, D4300C00003 and D4300C00004) * Females who are pregnant or breast feeding * Poorly controlled hypertension * Significant liver function test abnormalities or physical symptoms of hepatotoxicity * Significant infection * Gastrointestinal intolerance * Cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Had at Least 1 Adverse Event in Any Category | Entry in extension to end of study (variable duration; maximum 109 weeks) | AE = adverse event, bid = twice daily, IP = investigational product, qd = once daily, SAE = serious adverse event |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean DAS28-CRP Score | Weeks 0, 12, 24, 36 and 52 | 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. Number of participants are those with data at entry to this study (Week 0). As no imputation was applied, the numbers at subsequent visits are lower. bid = twice daily, CRP = C-reactive protein, qd = once daily |
| Mean mTSS Score | Weeks 0 and 52 | mTSS: modified total sharp score, a measure of structural progression based upon X-rays. Hand and foot joints are scored for erosions and joint space narrowing and the results summed to give a value between 0 and 488. A higher value represents more serious progression of the disease. Number of participants are those with data at entry to this study (Week 0). As no imputation was applied, the numbers at subsequent visits are lower. bid = twice daily, N/A = not applicable, qd = once daily |
| Mean HAQ-DI Score | Weeks 0, 12, 24, 36 and 52 | HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is then calculated by summing the category 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 a higher score indicating greater disability. Number of participants are those with data at entry to this study (Week 0). As no imputation was applied, the numbers at subsequent visits are lower. bid = twice daily, qd = once daily |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Czechia, Estonia, France, Germany, Hungary, India, Israel, Italy, Latvia, Lithuania, Mexico, Peru, Poland, Portugal, Romania, Russia, Serbia, Slovakia, South Africa, Spain, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Total of 1917 enrolled patients: 1346, 357 & 214 were allocated to the 100 mg twice daily (bid), 150 mg once daily (qd) and 100 mg qd groups, respectively (1343, 357 & 212 received at least 1 dose of investigational product). As this was a long-term extension study no specific end date was given. As such no patients were recorded as completers.
Pre-assignment details
A total of 5 patients did not receive treatment.
Participants by arm
| Arm | Count |
|---|---|
| Fostamatinib 100 mg Bid Oral treatment | 1,343 |
| Fostamatinib 150 mg qd Oral treatment | 357 |
| Fostamatinib 100 mg qd Oral treatment | 212 |
| Total | 1,912 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 129 | 18 | 19 |
| Overall Study | Dev. of study specific discont. criteria | 21 | 3 | 5 |
| Overall Study | e.g., project closure | 1,042 | 305 | 171 |
| Overall Study | Lack of therapeutic response | 99 | 16 | 10 |
| Overall Study | Lost to Follow-up | 14 | 5 | 4 |
| Overall Study | Severe non-compliance to protocol | 5 | 2 | 1 |
| Overall Study | Subject decision | 33 | 8 | 2 |
Baseline characteristics
| Characteristic | Fostamatinib 100 mg Bid | Fostamatinib 150 mg qd | Fostamatinib 100 mg qd | Total |
|---|---|---|---|---|
| Age, Continuous | 53 years STANDARD_DEVIATION 12 | 53 years STANDARD_DEVIATION 11.6 | 53 years STANDARD_DEVIATION 11.3 | 53 years STANDARD_DEVIATION 11.8 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 20 Participants | 11 Participants | 6 Participants | 37 Participants |
| Race/Ethnicity, Customized Asian | 40 Participants | 12 Participants | 7 Participants | 59 Participants |
| Race/Ethnicity, Customized Black or African American | 63 Participants | 11 Participants | 6 Participants | 80 Participants |
| Race/Ethnicity, Customized Indian or Pakistani | 54 Participants | 15 Participants | 22 Participants | 91 Participants |
| Race/Ethnicity, Customized Other | 74 Participants | 30 Participants | 30 Participants | 134 Participants |
| Race/Ethnicity, Customized White | 1092 Participants | 278 Participants | 141 Participants | 1511 Participants |
| Sex: Female, Male Female | 1086 Participants | 297 Participants | 193 Participants | 1576 Participants |
| Sex: Female, Male Male | 257 Participants | 60 Participants | 19 Participants | 336 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 466 / 1,343 | 68 / 212 | 98 / 357 |
| serious Total, serious adverse events | 153 / 1,343 | 12 / 212 | 31 / 357 |
Outcome results
Primary
Percentage of Patients Who Had at Least 1 Adverse Event in Any Category
AE = adverse event, bid = twice daily, IP = investigational product, qd = once daily, SAE = serious adverse event
Time frame: Entry in extension to end of study (variable duration; maximum 109 weeks)
Population: The full analysis set includes those patients who received at least 1 dose of investigational product, and were summarised according to treatment first received in this study (intention-to-treat principle).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fostamatinib 100 mg Bid | Percentage of Patients Who Had at Least 1 Adverse Event in Any Category | Any AE | 74.4 Percentage of patients |
| Fostamatinib 100 mg Bid | Percentage of Patients Who Had at Least 1 Adverse Event in Any Category | Any AE with outcome of death | 0.7 Percentage of patients |
| Fostamatinib 100 mg Bid | Percentage of Patients Who Had at Least 1 Adverse Event in Any Category | Any SAE (including events with outcome of death) | 11.4 Percentage of patients |
| Fostamatinib 100 mg Bid | Percentage of Patients Who Had at Least 1 Adverse Event in Any Category | Any AE leading to discontinuation of IP | 10.5 Percentage of patients |
| Fostamatinib 150 mg qd | Percentage of Patients Who Had at Least 1 Adverse Event in Any Category | Any AE leading to discontinuation of IP | 5.9 Percentage of patients |
| Fostamatinib 150 mg qd | Percentage of Patients Who Had at Least 1 Adverse Event in Any Category | Any AE | 70.3 Percentage of patients |
| Fostamatinib 150 mg qd | Percentage of Patients Who Had at Least 1 Adverse Event in Any Category | Any SAE (including events with outcome of death) | 8.7 Percentage of patients |
| Fostamatinib 150 mg qd | Percentage of Patients Who Had at Least 1 Adverse Event in Any Category | Any AE with outcome of death | 0.3 Percentage of patients |
| Fostamatinib 100 mg qd | Percentage of Patients Who Had at Least 1 Adverse Event in Any Category | Any AE leading to discontinuation of IP | 9.9 Percentage of patients |
| Fostamatinib 100 mg qd | Percentage of Patients Who Had at Least 1 Adverse Event in Any Category | Any AE with outcome of death | 0.5 Percentage of patients |
| Fostamatinib 100 mg qd | Percentage of Patients Who Had at Least 1 Adverse Event in Any Category | Any SAE (including events with outcome of death) | 5.7 Percentage of patients |
| Fostamatinib 100 mg qd | Percentage of Patients Who Had at Least 1 Adverse Event in Any Category | Any AE | 69.8 Percentage of patients |
Secondary
Mean DAS28-CRP Score
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. Number of participants are those with data at entry to this study (Week 0). As no imputation was applied, the numbers at subsequent visits are lower. bid = twice daily, CRP = C-reactive protein, qd = once daily
Time frame: Weeks 0, 12, 24, 36 and 52
Population: The full analysis set includes those patients who received at least 1 dose of investigational product, and were summarised according to treatment first received in this study (intention-to-treat principle).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fostamatinib 100 mg Bid | Mean DAS28-CRP Score | Week 0 (n=1247, 336, 198) | 4.5 Units on a scale | Standard Deviation 1.58 |
| Fostamatinib 100 mg Bid | Mean DAS28-CRP Score | Week 36 (n=581, 148, 68) | 3.9 Units on a scale | Standard Deviation 1.32 |
| Fostamatinib 100 mg Bid | Mean DAS28-CRP Score | Week 24 (n=800, 230 126) | 3.8 Units on a scale | Standard Deviation 1.3 |
| Fostamatinib 100 mg Bid | Mean DAS28-CRP Score | Week 52 (n=290, 28, 14) | 4.0 Units on a scale | Standard Deviation 1.25 |
| Fostamatinib 100 mg Bid | Mean DAS28-CRP Score | Week 12 (n=1018, 288, 160) | 3.8 Units on a scale | Standard Deviation 1.34 |
| Fostamatinib 150 mg qd | Mean DAS28-CRP Score | Week 24 (n=800, 230 126) | 3.7 Units on a scale | Standard Deviation 1.24 |
| Fostamatinib 150 mg qd | Mean DAS28-CRP Score | Week 0 (n=1247, 336, 198) | 3.8 Units on a scale | Standard Deviation 1.24 |
| Fostamatinib 150 mg qd | Mean DAS28-CRP Score | Week 12 (n=1018, 288, 160) | 3.6 Units on a scale | Standard Deviation 1.19 |
| Fostamatinib 150 mg qd | Mean DAS28-CRP Score | Week 36 (n=581, 148, 68) | 3.7 Units on a scale | Standard Deviation 1.24 |
| Fostamatinib 150 mg qd | Mean DAS28-CRP Score | Week 52 (n=290, 28, 14) | 3.8 Units on a scale | Standard Deviation 1.37 |
| Fostamatinib 100 mg qd | Mean DAS28-CRP Score | Week 52 (n=290, 28, 14) | 3.6 Units on a scale | Standard Deviation 1.22 |
| Fostamatinib 100 mg qd | Mean DAS28-CRP Score | Week 36 (n=581, 148, 68) | 3.9 Units on a scale | Standard Deviation 1.07 |
| Fostamatinib 100 mg qd | Mean DAS28-CRP Score | Week 0 (n=1247, 336, 198) | 3.9 Units on a scale | Standard Deviation 1.27 |
| Fostamatinib 100 mg qd | Mean DAS28-CRP Score | Week 24 (n=800, 230 126) | 3.6 Units on a scale | Standard Deviation 1.19 |
| Fostamatinib 100 mg qd | Mean DAS28-CRP Score | Week 12 (n=1018, 288, 160) | 3.7 Units on a scale | Standard Deviation 1.21 |
Secondary
Mean HAQ-DI Score
HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is then calculated by summing the category 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 a higher score indicating greater disability. Number of participants are those with data at entry to this study (Week 0). As no imputation was applied, the numbers at subsequent visits are lower. bid = twice daily, qd = once daily
Time frame: Weeks 0, 12, 24, 36 and 52
Population: The full analysis set includes those patients who received at least 1 dose of investigational product, and were summarised according to treatment first received in this study (intention-to-treat principle).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fostamatinib 100 mg Bid | Mean HAQ-DI Score | Week 36 (n=587, 149, 71) | 1.1 Units on a scale | Standard Deviation 0.67 |
| Fostamatinib 100 mg Bid | Mean HAQ-DI Score | Week 24 (n=817, 238, 132) | 1.1 Units on a scale | Standard Deviation 0.68 |
| Fostamatinib 100 mg Bid | Mean HAQ-DI Score | Week 0 (n=1271, 342, 201) | 1.2 Units on a scale | Standard Deviation 0.69 |
| Fostamatinib 100 mg Bid | Mean HAQ-DI Score | Week 12 (n=1061, 298, 166) | 1.1 Units on a scale | Standard Deviation 0.68 |
| Fostamatinib 100 mg Bid | Mean HAQ-DI Score | Week 52 (n=296, 28, 14) | 1.2 Units on a scale | Standard Deviation 0.68 |
| Fostamatinib 150 mg qd | Mean HAQ-DI Score | Week 24 (n=817, 238, 132) | 1.0 Units on a scale | Standard Deviation 0.67 |
| Fostamatinib 150 mg qd | Mean HAQ-DI Score | Week 0 (n=1271, 342, 201) | 1.0 Units on a scale | Standard Deviation 0.64 |
| Fostamatinib 150 mg qd | Mean HAQ-DI Score | Week 12 (n=1061, 298, 166) | 1.0 Units on a scale | Standard Deviation 0.63 |
| Fostamatinib 150 mg qd | Mean HAQ-DI Score | Week 36 (n=587, 149, 71) | 1.0 Units on a scale | Standard Deviation 0.65 |
| Fostamatinib 150 mg qd | Mean HAQ-DI Score | Week 52 (n=296, 28, 14) | 1.1 Units on a scale | Standard Deviation 0.64 |
| Fostamatinib 100 mg qd | Mean HAQ-DI Score | Week 52 (n=296, 28, 14) | 1.0 Units on a scale | Standard Deviation 0.73 |
| Fostamatinib 100 mg qd | Mean HAQ-DI Score | Week 36 (n=587, 149, 71) | 1.1 Units on a scale | Standard Deviation 0.62 |
| Fostamatinib 100 mg qd | Mean HAQ-DI Score | Week 0 (n=1271, 342, 201) | 1.0 Units on a scale | Standard Deviation 0.62 |
| Fostamatinib 100 mg qd | Mean HAQ-DI Score | Week 24 (n=817, 238, 132) | 0.9 Units on a scale | Standard Deviation 0.55 |
| Fostamatinib 100 mg qd | Mean HAQ-DI Score | Week 12 (n=1061, 298, 166) | 1.0 Units on a scale | Standard Deviation 0.63 |
Secondary
Mean mTSS Score
mTSS: modified total sharp score, a measure of structural progression based upon X-rays. Hand and foot joints are scored for erosions and joint space narrowing and the results summed to give a value between 0 and 488. A higher value represents more serious progression of the disease. Number of participants are those with data at entry to this study (Week 0). As no imputation was applied, the numbers at subsequent visits are lower. bid = twice daily, N/A = not applicable, qd = once daily
Time frame: Weeks 0 and 52
Population: The full analysis set includes those patients who received at least 1 dose of investigational product, and were summarised according to treatment first received in this study (intention-to-treat principle).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fostamatinib 100 mg Bid | Mean mTSS Score | Week 0 (n=480, 73, 37) | 30.5 Units on a scale | Standard Deviation 47.73 |
| Fostamatinib 100 mg Bid | Mean mTSS Score | Week 52 (n=223, 1, 6) | 30.1 Units on a scale | Standard Deviation 46.83 |
| Fostamatinib 150 mg qd | Mean mTSS Score | Week 0 (n=480, 73, 37) | 22.2 Units on a scale | Standard Deviation 32.89 |
| Fostamatinib 150 mg qd | Mean mTSS Score | Week 52 (n=223, 1, 6) | 0.5 Units on a scale | — |
| Fostamatinib 100 mg qd | Mean mTSS Score | Week 0 (n=480, 73, 37) | 20.8 Units on a scale | Standard Deviation 46.6 |
| Fostamatinib 100 mg qd | Mean mTSS Score | Week 52 (n=223, 1, 6) | 37.3 Units on a scale | Standard Deviation 67.7 |