Impact of Rituximab on Magnetic Resonance Imaging Evidence of Synovitis and Bone Lesions in Patients With Moderate or Severe Rheumatoid Arthritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 12
- 主要终点
- The primary endpoint fo the trial is change in 1.5 Tesla MRI erosion score (RAMRIS system) from baseline to Week 24.
研究概览
简要总结
The purpose of this study is to further investigate rituximab in the treatment of rheumatoid arthritis and to evaluate magnetic resonance imaging of the joints as a possible method to improve the evaluation of treatments.
详细描述
Rituximab is a monoclonal antibody that has been approved for the treatment of non-Hodgkin's B cell lymphoma (a type of cancer) and for certain patients with rheumatoid arthritis (RA) by the Food and Drug Administration (FDA). To date, more than 1000 subjects with rheumatoid arthritis have received rituximab in clinical studies.
Magnetic resonance imaging (MRI) is a modern and sensitive method of looking at joints in people with rheumatoid arthritis. It uses a magnetic field to create an image. The MRI takes an image in 3 dimensions and this provides a better picture for a physician to see more details.
There are two treatment groups in this study with equal numbers of patients assigned to each group. All the patients will receive their baseline Methotrexate and two intravenous infusions 2 weeks apart of one of the following:
- 1000 mg rituximab or
- placebo. Patients outcomes will be compared between the 2 groups. After week 24 (open label phase), the patients will receive rituximab if rheumatoid arthritis remains active.
All the patients will have MRI of their dominant hand and wrist with and without gadolinium performed at baseline, 12, 24 and 48 weeks on 1.5 Tesla MRI . Some patients will also have additional MRI of the same hand and wrist without gadolinium at the same time points on 0.2 Tesla MRI. Comparison of the images from the two machines will be performed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able and willing to give written informed consent
- •Age 18-80 years
- •Must have active rheumatoid arthritis for at least 12 weeks, but no more than 5 years.
- •Must be receiving treatment on an outpatient basis
- •Must have > 8 tender and swollen joints
- •Must have negative serum pregnancy test
- •Must have an inadequate response to MTX
- •Must have elevated serology parameters
- •Must have Positive RF or anti-CCP antibody, or radiographic evidence of at least one joint with definite erosion attributable to RA.
- •Stable use of Corticosteroids is permitted
- •Stable use of NSAIDs is permitted
排除标准
- •History of or current inflammatory joint disease
- •Functional class IV
- •Any surgical procedure within 12 weeks
- •Lack of peripheral venous access.
- •Pregnancy or breast feeding.
- •Significant cardiac or pulmonary disease.
- •Evidence of significant uncontrolled concomitant disease
- •Positive HIV
- •Known active infection of any kind
- •History of deep space/tissue infection
- •History of recurrent significant infection
- •Concomitant malignancies or previous malignancies
- •Any neurological, vascular or systemic disorder
- •History of drug, alcohol, or chemical abuse
- •Inability to comply with study and follow-up procedures
- •History of a severe allergic or anaphylactic reaction to a biologic agent
- •Previous treatment with more than one biologic agent for RA. Patients must not have received a biologic agent within 2 months prior to the Baseline visit, except for etanercept, abatacept and anakinra for which a one month washout prior to Baseline visit is acceptable
- •Previous treatment with an anti-alpha 4 integrin antibody or co-stimulation modulator.
- •Previous treatment with any cell depleting therapies.
- •Treatment with any investigational agent within 28 days
- •Receipt of a live/attenuated vaccine within 28 days
- •Ongoing use of high dose steroids (>10mg/day)
- •Inra-articular or parental glucocorticoids within 4 weeks prior to baseline.
- •Intolerance or contraindications to i.v. glucocorticoids.
结局指标
主要结局
The primary endpoint fo the trial is change in 1.5 Tesla MRI erosion score (RAMRIS system) from baseline to Week 24.
时间窗: 24 weeks
次要结局
- Change from Baseline in 1.5 Tesla MRI synovitis score (RAMRIS system) at Week 12.(12 weeks)
- Change from Baseline in 1.5 Tesla MRI bone edema and total score (RAMRIS system) at Week 24.(24 weeks)
- Change from Baseline in 1.5 Tesla MRI bone edema, bone erosion and total score (RAMRIS system) at Week 12 and Week 48.(12 and 48 weeks)
- Proportion of patients at Week 48 without new bone erosions on 1.5 Tesla MRI.(48 weeks)
- Change from baseline in total Genant modified Sharp score on conventional radiographs at Week 24 and 48.(24 and 48 weeks)
- Change in Disease Activity Score (DAS 28) from Baseline to Week 24 and 48.(24 and 48 weeks)
- ACR remission and responder rates (20%, 50%, &)%) at Week 24 and 48.(24 and 48 weeks)
- Change from Baseline in functional assessments according to the HAQ scores at 24 and 48 Weeks.(24 and 48 weeks)
- Difference between relative results from conventional high-field strength 1.5 Tesla MRI and 0.2 Tesla dedicated extremity MRI in detection and grading of bone erosions, bone edema, and synovitis at Baseline and in Week 12,24, and 48 (C-scan validation).(12, 24 and 48 weeks)