A Multi-Centered, Randomized, Double-Blind, Placebo Controlled Study Assessing the Add-on Effect of Oral Steroids in Relapsing Remitting Multiple Sclerosis Subjects Treated With Glatiramer Acetate (GA)
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 414
- 主要终点
- Percent Change From Baseline to Termination in Normalized Brain Volume Measured According to the SIENA (Structural Imaging Evaluation Using Normalization of Atrophy) Method
研究概览
简要总结
This is a study evaluating the effect on brain volume of daily glatiramer acetate (GA) and add-on pulse steroids.
详细描述
One interim analysis was planned for possible early termination due to proven efficacy when 75% of the preplanned 500 (approx. 375 patients) recruited patients completed the entire study duration or early discontinued.
In addition to the stopping rule already given for proven efficacy, the sponsor was also interested in examining the data for futility (i.e., absence of the desired treatment effect) with the view to terminating the trial if an "insufficient" effect of the treatment is seen. The reasons why the need for futility arose were:
- Recruitment difficulties
- Increasing dropout rate
- Budgetary constraints
The primary efficacy measure is defined as the percent change from baseline to termination (Month 36 or Early Termination) in normalized brain volume (Brain Atrophy) measured according to the SIENA (Structural Imaging Evaluation using Normalization of Atrophy) method. However, since not many patients had completed the entire study at the time of futility analysis, it was the sponsor's decision that the futility analysis be performed on patients with MRI scans at months 24 or 36 or at early termination visits - the latest available.
Based on the recalculation of study power (probability is unconditioned on the interim result and provide the real power of the study if designed anew), conditional power (based on the interim results) and risk assessment of a false negative, the Data Monitoring Committee agreed that the study should be terminated early.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinically definite multiple sclerosis (CDMS) according to Poser (Ann. Neurol. 1983) or McDonald (Ann. Neurol. 2001)
- •Subjects eligible for GA treatment based on the investigator's clinical assessment and according to the current indication.
- •Subjects must have a relapsing remitting disease course.
- •Subjects must have had at least 1 documented relapse within the last year prior to study entry.
- •Subjects may be male or female. Women of childbearing potential must practice an acceptable method of birth control. Acceptable methods include oral contraceptive, contraceptive patch, long-acting injectable contraceptive, double-barrier method (condom or intrauterine device [IUD] with spermicide), or partner's vasectomy.
- •Subjects must be between the ages of 18 and 55 years inclusive.
- •Subjects must be ambulatory, with a Kurtzke Expanded Disability Status Scale (EDSS) score between 0 and 5.0 inclusive.
- •Subjects must be willing and able to give written informed consent prior to entering the study.
排除标准
- •Long-term glatiramer acetate users who have been on therapy within 6 months of the baseline magnetic resonance imaging (MRI). New glatiramer acetate users who have initiated therapy for more than 6 weeks prior to the baseline MRI.
- •Previous use of cladribine.
- •Previous use of mitoxantrone.
- •Use of digitalis at study entry.
- •Previous use of immunosuppressive agents (such as azathioprine, cyclophosphamide or mycophenolate mofetil) in the last 6 months prior to screening.
- •Use of experimental or investigational drugs, including intravenous (IV) immunoglobulin within 6 months prior to screening.
- •Use of interferon agents within 1 month prior to the baseline MRI.
- •Use of corticosteroids (IV, intramuscular [IM] and/or by mouth [PO]) within 30 days prior to the baseline MRI.
- •Chronic corticosteroid (IV, IM and/or PO) treatment (more than 30 consecutive days) in the 6 months prior to the screening visit.
- •Subjects with diabetes.
- •Previous total body irradiation or total lymphoid irradiation.
- •Pregnancy or breast feeding.
- •Significant medical or psychiatric condition that affects the subject's ability to give informed consent, or to complete the study, or any condition which the investigator feels may interfere with participation in the study (e.g. alcohol or drug abuse).
- •Other diseases that can cause brain atrophy (ex. neurodegenerative disorder, cerebrovascular disease, history of alcohol abuse).
- •Bone density less than -2.5 standard deviations (SD) (osteoporosis).
- •A known history of sensitivity to mannitol.
- •Contraindication to, or known history of, sensitivity or severe reaction to steroids.
- •A known history of sensitivity to gadolinium.
- •Inability to successfully undergo MRI scanning.
- •Previous use of natalizumab.
研究组 & 干预措施
GA + Placebo
Glatiramer acetate (GA) 10mg as a subcutaneous injection daily, plus a placebo to mimic prednisone given daily.
干预措施: Glatiramer Acetate (Drug)
GA + Placebo
Glatiramer acetate (GA) 10mg as a subcutaneous injection daily, plus a placebo to mimic prednisone given daily.
干预措施: Placebo (Drug)
GA + Prednisone
Glatiramer acetate (GA) 20mg daily as a subcutaneous injection, plus 1250 mg of prednisone daily.
干预措施: Glatiramer Acetate (Drug)
GA + Prednisone
Glatiramer acetate (GA) 20mg daily as a subcutaneous injection, plus 1250 mg of prednisone daily.
干预措施: Prednisone (Drug)
结局指标
主要结局
Percent Change From Baseline to Termination in Normalized Brain Volume Measured According to the SIENA (Structural Imaging Evaluation Using Normalization of Atrophy) Method
时间窗: Day 0, latest scan at month 24, 36 or early termination visit
Results represent the database as of January 29, 2009. Brain volume was measured at baseline and at months 24, 36 and at early termination visits by magnetic resonance imaging (MRI). Brain atrophy was measured by comparing the change in brain volume from baseline to the latest scan at the three during study timeframes. SIENA is a fully automated method of analyzing longitudinal brain change. Adjusted (least square) mean values are presented.
次要结局
- Cumulative Number of Enhancing Lesions at Months 12, 24 and 36(Months 12, 24, and 36)
- Change From Baseline to Month 36 or Early Termination Visit in Volume of T2-Lesions(Day 0, Month 36 or the early termination visit)
- Change From Baseline to Month 36 or Early Termination Visit in Volume of Hypointense Lesions(Day 0, Month 36 or early termination visit)