Pilot Open-label Study of the Effect of Etanercept on Vascular Inflammation in Patients With Active Rheumatoid Arthritis
概览
- 阶段
- 4 期
- 干预措施
- etanercept
- 疾病 / 适应症
- Rheumatoid Arthritis
- 发起方
- Innovaderm Research Inc.
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Target to background ratio (TBR) from the ascending aorta
- 状态
- 终止
- 最后更新
- 9年前
概览
简要总结
The primary goal of this preliminary project is to study the effect of etanercept, a medicine approved by Health Canada for the treatment of rheumatoid arthritis, on the inflammation of certain blood vessels. In particular, the inflammation of the aorta and the carotid arteries will be studied.
This study's goal is to determine if etanercept (that blocks TNF (tissue necrosis factor) alpha) could have an effect on blood vessel inflammation. As well, the information from this study will be used to determine the number of patients to recruit in a future study.
This study will evaluate the effect of etanercept on 10 patients with rheumatoid arthritis at one rheumatology clinic in Montreal. The 10 patients will be recruited at the Montreal Rheumatology Institute (Institut de Rhumatologie de Montréal) and the images of the blood vessels taken at a medical imaging center will be analyzed by the Montreal Heart Institute.
To evaluate vascular inflammation subjects will undergo a PET scan (Positron Emission Tomography).
详细描述
This study is a 16 week, single center, open label trial, to study the effect of etanercept on vascular inflammation of the ascending aorta and carotid arteries in patients with rheumatoid arthritis (RA). Patients with active RA already receiving methotrexate for at least 3 months will receive etanercept for 16 weeks. Etanercept will be administered sub-cutaneously using the dose approved in the Canadian product monograph for RA (50 mg every week). Patients will continue methotrexate at a stable dose during the study unless a dose reduction or cessation is required as judged necessary by the study investigator. Positron Emission Tomography (PET) Scan will be performed at baseline and after16 weeks of study treatment with etanercept. At the end of the study, all PET Scan images will be analyzed in a blinded manner by the Montreal Heart Institute core laboratory. Safety will be assessed using adverse events collection and laboratory hematology and chemistry analysis (screening and Week 4) and pregnancy test.
研究者
入排标准
入选标准
- •Patient is 18 to 80 years of age, inclusive.
- •Patient's weight at screening is a maximum of 180 kg.
- •Patient has a clinical diagnosis of active RA for at least 3 months defined as:
- •2-4 joints with active synovitis OR
- •1 joint with active synovitis and a high sensitivity C-reactive protein higher than the upper limit.
- •Patient with active synovitis despite treatment for at least 3 months with a dose of methotrexate of at least 15 mg per week.
- •Patient is eligible to receive etanercept according to Canadian Product Monograph.
- •Medications used to control angina, hypertension, serum lipids and any medication that can have an effect on inflammation must be on a stable dose for at least 8 weeks before baseline.
- •Patient with an ascending aorta atherosclerotic plaque inflammation target-to-background ratio of 1.6 or more as determined by 18-FDG uptake measured by PET scanning at pre-enrolment.
- •Female patients of childbearing potential must have a negative serum pregnancy test at the Screening visit.
排除标准
- •Patient has a history of an allergic reaction or significant sensitivity to constituents of study drug (etanercept), including latex (a component of the pre-filled syringe).
- •Patient has chronic or recurrent infection or history of listeriosis, histoplasmosis or any other invasive fungal or mycobacterial infections, treated or untreated Tuberculosis (TB), persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous anti-infectives drug within 30 days prior to the Day 0 visit or oral anti-infectives within 14 days prior to the Day 0 visit.
- •Patient used any non-biological investigational agents within 30 days or 5 half-lives prior to Day 0 visit (whichever is longer).
- •Patient who has used any biological therapy for the treatment of RA less than 3 months (90 days) or 5 half-lives prior to Day 0 visit (whichever is longer) or patient has received Anakinra/Kineret within the last 2 weeks prior to the Day 0 visit or is likely to receive Anakinra/Kineret during the course of the study.
- •Patient has used a non-biological systemic therapy for the treatment of RA less than 30 days before Day 0, other than methotrexate.
- •Patient is taking or requires oral or injectable corticosteroids at a dose equivalent to more than 5 mg of prednisone daily within 30 days of Day 0 and during the study. Inhaled corticosteroids for stable medical conditions are allowed. Patients taking oral or injectable corticosteroids must be on a stable dose for at least 3 months before Day
- •Patient for whom the treating physician is planning to change the dose of methotrexate or oral corticosteroids during the study.
- •Patient has used a systemic immunosuppressor (eg. Azathioprine, 6-mercaptopurine) less than 30 days before Day
- •Patient who has another musculoskeletal disease that could interfere with or prevent with joint examination
- •Patient who had a myocardial infarction or hospitalization for a cardiac condition within the past 12 weeks.
研究组 & 干预措施
Methotrexate and Etanercept
Patients already taking Methotrexate prior to the study will continue taking 15 mg weekly and start Etanercept 50 mg every week for 16 weeks
干预措施: etanercept
结局指标
主要结局
Target to background ratio (TBR) from the ascending aorta
时间窗: 16 weeks
Change from baseline in target (atherosclerotic plaque) to background (blood) ratio (TBR) from the ascending aorta.
次要结局
- TBR from the mean of both carotid arteries(16 Weeks)
- High Sensitivity C-reactive protein (hsCRP)(16 weeks)
- Count of swollen and tender joints(16 weeks)
- Correlation of TBR from the ascending aorta with hsCRP(16 weeks)
- Correlation of TBR from the mean of both carotid arteries with hsCRP(16 weeks)
- Correlation of TBR from the ascending aorta with swollen and tender joint count(16 weeks)
- Correlation of TBR from the carotid arteries with swollen and tender joint count(16 weeks)