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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 198
- 试验地点
- 1
- 主要终点
- OMERACT RAMRIS Synovitis Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)
研究概览
简要总结
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.
详细描述
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.
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
- •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)
- •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.
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
- •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
研究组 & 干预措施
Dosing Group A
Oral treatment and subcutaneous injection.
干预措施: Fostamatinib (Drug)
Dosing Group A
Oral treatment and subcutaneous injection.
干预措施: Placebo of Adalimumab (Drug)
Dosing Group D
Oral treatment and subcutaneous injection.
干预措施: Adalimumab (Drug)
Dosing Group D
Oral treatment and subcutaneous injection.
干预措施: Placebo of Fostamatinib (Drug)
Dosing Group E
Placebo bid for 6 weeks followed by switch to 100 mg fostamatinib bid for 24 weeks, plus placebo subcutaneous injection every 2 weeks.
干预措施: Fostamatinib (Drug)
Dosing Group E
Placebo bid for 6 weeks followed by switch to 100 mg fostamatinib bid for 24 weeks, plus placebo subcutaneous injection every 2 weeks.
干预措施: Placebo of Fostamatinib (Drug)
Dosing Group E
Placebo bid for 6 weeks followed by switch to 100 mg fostamatinib bid for 24 weeks, plus placebo subcutaneous injection every 2 weeks.
干预措施: Placebo of Adalimumab (Drug)
结局指标
主要结局
OMERACT RAMRIS Synovitis Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)
时间窗: 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.
次要结局
未报告次要终点