A One-Year Prospective, Randomized, Placebo-Controlled, Double-Blind, Phase II/III Safety Trial of Combination Therapy With IFN Beta-1a (Avonex) and Mycophenolate Mofetil (Cellcept) in Early Multiple Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- The primary objective of this safety/mechanistic study is to determine the safety and tolerability of oral Cellcept when used in combination with weekly intramuscular Avonex in early MS. Early MS for this study is defined at a definite diagnosis of less
研究概览
简要总结
- To determine the safety and tolerability of oral Cellcept when used in combination with weekly intramuscular Avonex in early MS.
- To document changes in exacerbation frequency,
- To document the incidence of mild, moderate, and severe exacerbations in the treated groups (categorical analysis),
- To document changes in the level of sustained disability as measured by the expanded disability status score (EDSS) and ambulation index (AI),
- To document changes in quality of life measures,
- To assess fatigue with the validated fatigue assessment inventory,
- Neuroimmunological studies:At baseline, 6 and 12 months after treatment
详细描述
Design: Uni-center, double-blind, randomized, placebo-controlled study of Avonex + placebo vs Avonex + Cellcept
Rationale: A number of immunopathogenic mechanisms have been hypothesized to figure prominently in the processes that culminate in the characteristic plaque lesion. These include the role of cytokines, chemokines, excitatory amino acids, free radicals, superoxides, and nitric oxide synthetase products. Recognizing that the disease process in MS involves a cascade of biological events, sets the stage for strategically targeting specific immunopathogenetic steps through rational combination therapy regimens. We now propose a combination clinical trial utilizing Avonex and mycophenolate mofetil (MMF), a novel agent with a broad spectrum of anti- inflammatory mechanisms.
- Study population: MS patients who have been diagnosed with clinically definite, laboratory supported definite, or monosymptomatic MS meeting CHAMPS criteria ref , of either sex, who are between the ages of 21 and 50 inclusive.
- Treatment Groups: 12 patients in each group, ALL patients on Intramuscular Avonex. Cellcept/Placebo will be started at 250mg bid for one week and then escalated by 250mg bid until a target dose of 1000mg bid is achieved and Avonex 30 mcg IM q week
Patients also see an examining physician every three months, have brain MRI scans done every other month and donate WBCs through a procedure called leukapheresis (done every six months).
- Efficacy Parameters/Evaluations: EDSS, PSAT, MSFC and MRI, relapse rate and safety measures
- Safety Parameters/Evaluations: Safety will be assessed by virtue of changes in T2/FLAIR lesions (number and volume) and in gadolinium enhancements (measured at 6 and 12 months after treatment initiation) compared to baseline measurements derived from one pretreatment run- in scan. In addition, a variety of clinical assessments will be performed for the period of 12 months of treatment. We will enroll 12 patients in each group (24 total)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 21 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Between the ages of 21-45 inclusive
- •Clinically definite, laboratory supported definite relapsing MS of less than or equal to two years in duration or monosymptomatic MS meeting CHAMPS criteria ref .
- •At least one exacerbation in the preceding two years
- •Written informed consent.
排除标准
- •Primary progressive, secondary progressive or progressive relapsing MS.
- •Corticosteroids during the 60 days prior to study entry.
- •Treatment with plasma exchange within 90 days of preenrollment.
- •No prior exposure to total lymphoid irradiation.
- •No prior use of interferons, monoclonal antibodies, glatiramer acetate, methotrexate or other immunomodulatory drugs
- •A clinical relapse within 60 days prior to enrollment.
- •Pregnant/breastfeeding.
- •Patients with major medical illnesses.
- •Cognitive impairment interfering with ability to comply with the protocol.
- •Patients who need to remain on any contraindicated medication.
- •Inability to undergo MRI scan
- •On intravenous immunoglobulin protocol
- •HIV+ or RPR+
- •Females of childbearing age who have not undergone a sterilization procedure must be willing to practice effective birth control.
结局指标
主要结局
The primary objective of this safety/mechanistic study is to determine the safety and tolerability of oral Cellcept when used in combination with weekly intramuscular Avonex in early MS. Early MS for this study is defined at a definite diagnosis of less
次要结局
- Pharmacodynamics.
- Genetic Studies.
- To document changes in exacerbation frequency
- To document the incidence of mild, moderate, and severe exacerbations in the treated groups.
- To document changes in the level of sustained disability as measured by the expanded disability status score (EDSS) and ambulation index (AI) as assessed by the Kaplan-Meier methodology.
- To document changes in quality of life measures (MSQOL-54, SF-36, and Beck's Depression Index).
- To assess fatigue with the validated fatigue assessment inventory
- Neuroimmunological studies:At baseline, 6 and 12 months after treatment.
研究者
Elliot Frohman
Professor
University of Texas Southwestern Medical Center