Health Condition 1: null- Rheumatoid Arthritis
Conditions
Interventions
Intervention1: Fostamatinib Disodium: 100 mg twice daily
Control Intervention1: Placebo: 100 mg twice daily
Sponsors
AstraZeneca Research and Development
Eligibility
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent, prior to any study-specific procedures. NB: Patients agreeing to participate in the optional exploratory biomarker and/or exploratory genetic research must provide a separate informed consent. 2. Male or female aged 18 and over with a diagnosis of RA after the age of 16 according to the revised (1987) criteria of the American College of Rheumatology (see Appendix E for criteria). NB: Women of childbearing potential may be included only if using acceptable contraceptive methods (see Appendix H for definitions). All females must have 2 negative pregnancy tests, at least 14 days apart, prior to randomization. 3. Active RA defined as: − 6 swollen joints and 6 tender/painful joints (from 28 joint count) and either: − ESR 28 mm/h, or − CRP 10 mg/L. 4. At least 1 of the following: − Documented history of positive rheumatoid factor − Current presence of rheumatoid factor − Radiographic erosion within 12 months prior to enrolment − Presence of serum anti-cyclic citrullinated peptide antibodies (anti-CCP). 5. Treatment with oral, subcutaneous or intramuscular methotrexate for at least 6 months prior to randomisation. The dose and means of administering methotrexate must have been stable between 7.5 mg and 25 mg per week for at least 6 weeks prior to randomisation. Patients receiving the lower doses of methotrexate (7.5 mg and 10 mg) should be doing so as a result of a documented history of intolerance to higher doses of methotrexate.
Exclusion criteria
Exclusion criteria: 1. Females who are pregnant or lactating. 2. Any systemic inflammatory conditions (other than RA), connective tissue disease or chronic pain disorders that may interfere with the interpretation of the outcome data. Examples include psoriatic arthritis, reactive arthritis, gout, systemic lupus erythematosus (SLE), polymyalgia rheumatica and/or temporal arteritis, Lymes disease, fibromyalgia and chronic fatigue syndromes. 3. American College of Rheumatology functional Class IV (see Appendix F) or wheelchair/bed-bound. 4. Uncontrolled or poorly controlled hypertension defined as 140 mmHg systolic and/or 90 mmHg diastolic at baseline (Visit 2) with or without current anti-hypertensive treatment. NB: If above these limits at Visit 1, anti-hypertensive treatment may be initiated according to local guidelines and patients may be considered eligible providing BP has been controlled before randomisation, with the interval between screening (Visit 1) and baseline (Visit 2) not exceeding 4 weeks. If control of hypertension is not achieved within this period patients should be considered ineligible and not re-screened again. Note that the mean of the 2nd and 3rd BP measurements should be used (see Section 6.4.8). 5. Absolute neutrophil count (ANC) 1500/mm3 or 1.5 x 109/L. If a patient has findings marginally below this limit, re-screening is allowed, at the investigators discretion, within the 28 day period between Visit 1 and 2. 6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 1.2 x upper limit of normal (ULN), or bilirubin 1.2 x ULN. If a patient has AST or ALT 1.2 x ULN but 2 x ULN, re-screening is allowed, at the investigators discretion, within the 28-day period between Visit 1 and 2. NB: Patients with documented Gilberts Syndrome may be included at the discretion of the investigator where liver function tests are normal except for an elevation of unconjugated (indirect) bilirubin consistent with Gilberts Syndrome, and where haemolysis has been excluded. 7. History of liver function abnormality requiring investigation, drug induced liver injury, chronic liver disease, excessive alcohol consumption or chronic alcohol induced disease. 8. Evidence of recent or significant CV disease defined as: infarction, unstable angina, cerebrovascular accident, pulmonary embolism, or heart failure New York Heart Association Class III or IV (see Appendix Q). 9. Evidence of active or recent infection including: − Positive serological test for hepatitis B or hepatitis C (patients may be included if confirmed hepatitis C recombinant immunoblot assay negative or hepatitis C virus RNA negative [qualitative]), or patients with suspected human immunodeficiency virus (HIV). − Treatment with intravenous antibiotics within previous month prior to randomisation, oral antibiotics within 2 weeks prior to randomisation or current evidence of a clinically significant active infection. 10. Evidence of tuberculosis (TB) infection. − Patients should have a chest X-ray, current or taken within the previous 3 months, which excludes active pulmonary TB or other pulmonary infection. − Patients should have a negative TB skin test (negative means 5 mm induration). − If the skin test is positive in an unvaccinated patient an appropriate prophylactic TB regimen must be documented and patient
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Proportion of patients achieving ACR20 response at Week 24 2. Change in mTSS at Week 24 Timepoint: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. ACR20, ACR50, ACR70, major clinical response, ACR-N, individual 2. HAQ-DI score; HAQ-DI response, individual dimensions of HAQ-DI 3. DAS28 response, DAS28 EULAR response criteria, DAS 4. mTSS, radiographic erosion score (ES) and joint space narrowing (JSN). Timepoint: 52 weeks | — |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Estonia, France, Germany, Hungary, India, Latvia, Mexico, Peru, Poland, Romania, Russian Federation, Serbia, Slovakia, Spain, Ukraine, United Kingdom, United States of America
Contacts
Public ContactSuneela Thatte
Quintiles
Outcome results
None listed