(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 Adalimumab Monotherapy in Patients With Active Rheumatoid Arthritis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 644
- 试验地点
- 1
- 主要终点
- DAS28-CRP Score - Change From Baseline to Week 6 Compared to Placebo
研究概览
简要总结
The purpose of the study is to evaluate the improvements in signs and symptoms of rheumatoid arthritis (RA) for fostamatinib compared to placebo or adalimumab in patients who are Disease-Modifying anti-rheumatic drug (DMARD) naïve, DMARD intolerant or have had an inadequate response to DMARDs. The study will last for approximately six months
详细描述
Sub-study:
Full title: Optional Genetic Research
Date: 10 September 2010
Version: 1
Objectives: To collect and store, with appropriate consent , DNA samples for future exploratory research into genes/genetic variation that may influence response (ie, absorption, distribution, metabolism and excretion, safety, tolerability and efficacy) to fostamatinib disodium and/or adalimumab; and/or susceptibility to, progression of and prognosis of RA
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged 18 and over
- •Active rheumatoid arthritis (RA) diagnosed after the age of 16 and 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) and 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)
排除标准
- •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
- •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
研究组 & 干预措施
Dosing Group A
Oral treatment and subcutaneous injection
干预措施: Fostamatinib and placebo injections (Drug)
Dosing Group B
Oral treatment and subcutaneous injection
干预措施: Fostamatinib and placebo injections (Drug)
Dosing Group C
Oral treatment and subcutaneous injection
干预措施: Fostamatinib and placebo injections (Drug)
Dosing Group D
Oral treatment and subcutaneous injection
干预措施: Adalimumab and placebo of fostamatinib (Drug)
Dosing Group E
Oral treatment and subcutaneous injection
干预措施: Placebo of fostamatinib, fostamatinib, and placebo injections (Drug)
结局指标
主要结局
DAS28-CRP Score - Change From Baseline to Week 6 Compared to Placebo
时间窗: Baseline and 6 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. Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicative of a better clinical condition. ANCOVA = analysis of covariance, BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, QD = once a day, SC = subcutaneous.
DAS28-CRP Score - Change From Baseline to Week 24 Compared to Adalimumab
时间窗: Baseline and 24 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. Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicative of a better clinical condition. Non-responder imputation has been applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, QD = once a day, SC = subcutaneous.
次要结局
- HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Placebo at Week 6(Baseline and 6 weeks)
- HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Adalimumab at Week 24(Baseline and 24 weeks)
- SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Adalimumab at Week 24(Baseline and 24 weeks)
- SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Adalimumab at Week 24(Baseline and 24 weeks)
- DAS28 EULAR Response at Week 6(6 weeks)
- DAS28 EULAR Response at Week 24(24 weeks)
- Proportion of Patients Achieving ACR20 up to Week 24(6 and 24 weeks)
- Proportion of Patients Achieving ACR50 up to Week 24(6 and 24 weeks)
- Proportion of Patients Achieving ACR70 up to Week 24(6 and 24 weeks)
- ACRn - Comparison Between Fostamatinib and Placebo at Week 6(Baseline and 6 weeks)
- ACRn - Comparison Between Fostamatinib and Adalimumab at Week 24(Baseline and 24 weeks)