A Phase II, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of Abatacept in Adults With Relapsing-remitting Multiple Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 21
- 主要终点
- Mean Number of New Inflammatory MRI Lesions Per Monthly Scans
研究概览
简要总结
The ACCLAIM study is testing whether the medication "abatacept" can be of benefit to patients with relapsing-remitting multiple sclerosis (MS). Although abatacept is an investigational medication for MS, it is not a new drug. Abatacept has been approved by the FDA to treat rheumatoid arthritis.
详细描述
MS is a chronic autoimmune disease in which blood cells that are supposed to protect the body from infection mistakenly attack the body's own tissue. In MS, the target of this attack is a protein called myelin that coats nerves throughout the body. Damage to this protective layer can lead to loss of neurologic function.
There are a number of treatments available to MS patients. Interferon beta, Copaxone, and other drugs can delay the worsening of the disease in some patients. For other patients, more aggressive treatment with chemotherapy drugs such as cyclophosphamide or azathioprine are needed. These drugs attempt to slow the disease by limiting the activity of the entire immune system. Because of this, they can often have serious side effects.
This study evaluates the efficacy of abatacept in the treatment of relapsing-remitting MS. In the first phase of the study, all participants will receive 8 intravenous treatments over a period of 24 weeks. Then, if a participant remains eligible, they will enter the second phase of the study and will receive another 8 treatments over the following 24 weeks. Two-thirds (2 out of 3) of participants will receive the study drug abatacept in the first phase, and then an inactive form (placebo) of the drug in the second phase. The remaining one-third (1 in 3) will get the placebo first, then the study drug in the second phase if they remain eligible. Therefore, all participants in the ACCLAIM trial will have the opportunity to receive the study drug abatacept if they remain healthy during the study. Participants will be asked to return for a follow-up visit 12 weeks after all treatments have been completed.
Regular appointments scheduled during the trial will be used to monitor participants' health and progress in the study. These appointments will include: physical and neurological exams, blood tests and motor function assessments. A total of 11 magnetic resonance imaging (MRI) procedures are scheduled during the study. The study medication and procedures related to the study will be provided at no expense to the participant.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinically definite Relapsing-remitting Multiple Sclerosis (RRMS) meeting McDonald's criteria
- •Expanded Disability Status Scale (EDSS) scores between 0 and 5
- •Active disease as defined by at least one of the following criteria:
- •One or more documented clinical exacerbations in the past year prior to visit -2
- •One or more gadolinium (Gd)-enhanced MRI lesions in the past year
- •Willingness to forego available MS therapies
- •Ability and willingness to provide informed consent and comply with study requirements and procedures
排除标准
- •Normal brain MRI at week -5 scan
- •Females who are pregnant, intending pregnancy, or lactating, and unwilling to undergo pregnancy testing
- •Females who are unwilling to use approved methods of contraception for the duration of the study
- •Any chronic medical disease, other than MS, that compromises organ function
- •Active infection
- •Diagnosis of secondary or primary progressive MS
- •Previous treatment with cyclophosphamide, mitoxantrone, cladribine, or rituximab at any time
- •Previous treatment with abatacept within the last 52 weeks prior to visit -2
- •Previous treatment with systemic steroids, interferon, Copaxone, mycophenolate, or other immunosuppressive medications within the last 4 weeks prior to visit -2
- •Previous treatment with Natalizumab within the last 26 weeks prior to visit -2
- •Previous vaccination with live vaccine, or previous treatment with fingolimod, within the last 8 weeks prior to visit-2
- •Diagnosis of malignancy other than basal cell carcinoma or cervical carcinoma in situ
- •Claustrophobia or other contraindications to Gd-enhanced MRI
- •Positive for human immunodeficiency virus (HIV) serology
- •Positive for hepatitis B surface antigen (HBsAg)
- •Positive for hepatitis C virus (HCV) serology
- •Purified protein derivative (PPD)-tuberculin skin test result greater than 5 mm induration
- •Hemoglobin less than 10.5 gm/dL
- •Platelets less than 100K/µL
- •Absolute lymphocyte count less than 700 cells/μL
- •Serum creatinine greater than 1.20 mg/dL
- •eGFR (estimated glomerular filtration rate) less than 60 mL/min/1.73 m^2
- •IgG anti-cardiolipin antibody greater than 15 GPL U/mL
- •Previous participation in another interventional clinical trial within the past 4 weeks prior to visit -2
- •Allergy or sensitivity to any component of abatacept
- •The presence of any medical condition that the investigator deems incompatible with participation in the trial
研究组 & 干预措施
Abatacept
Receives abatacept during first course of treatment, switching to placebo during extension phase.
干预措施: abatacept (Biological)
Abatacept
Receives abatacept during first course of treatment, switching to placebo during extension phase.
干预措施: Placebo (Drug)
Placebo, followed by abatacept
Receives a placebo for first course of treatment, switching to abatacept in the extension phase.
干预措施: abatacept (Biological)
Placebo, followed by abatacept
Receives a placebo for first course of treatment, switching to abatacept in the extension phase.
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Number of New Inflammatory MRI Lesions Per Monthly Scans
时间窗: Weeks 8-24
The mean number of new inflammatory MRI lesions obtained on scans every 4 weeks from Week 8 to Week 24, adjusted for differences between subjects before treatment by subtracting the number of new inflammatory lesions observed from the week -1 MRI scan . An inflammatory lesion is defined as a gadolinium (Gd)-enhancing lesion that shows hyperintensity on postcontrast but no hyperintensity on noncontrast T1 images. A new inflammatory lesion is one that was not present on the previously scheduled MRI scan. If the previously scheduled MRI scan was missing, the scan was compared to the last available MRI.
次要结局
- Percent Brain Volume Change(Week -1 to Week 24)
- Mean Number of New Inflammatory Lesions in 8-week Intervals(Week 8 to Week 24)
- Lesion Volume Accumulation on T2-weighted MRI Scans Over 24 Weeks(Week -1 to Week 24)
- Absolute Number of New Inflammatory MRI Lesions on Monthly Scans(Weeks 4-24)
- Number of Participants Progressing on the EDSS Scale by at Least 1 Point(Week 24 to Week 64)
- Annualized Relapse Rate(Week -1 to Week 24)
- Mean Change in the MSFC Over 24 Weeks of Treatment(Week -1 to Week 24)
- Mean Number of New Inflammatory MRI Lesions Per Scan During the Extension Phase(Weeks 36 and 52)
- Lesion Volume Accumulation on T2-Weighted MRI Scans Between 24 Weeks and 52 Weeks(Week 24 to Week 52)
- Percent Brain Volume Change Between 24 Weeks and 52 Weeks(Week 24 to Week 52)
- Annualized Relapse in Extension Phase(Week 24 to Week 64)
- Mean Change in the MSFC in Extension Phase(Week 24 to Week 52)