NCT00813709已完成3 期
Double-blind Extension of the Study 27025 (REFLEX) to Obtain Long-term Follow-up Data in Patients With Clinically Definite MS and Patients With a First Demyelinating Event at High Risk of Converting to MS, Treated With Rebif® New Formulation (REFLEXION)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 402
- 试验地点
- 2
- 主要终点
- Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score up to 36 Months
研究概览
简要总结
REFLEXION is a double blind extension of the study 27025 (NCT00404352) (REFLEX). The purpose of the study is to obtain long-term follow-up data in subjects with clinically definite multiple sclerosis (MS) and subjects with a first demyelinating event at high risk of converting to MS, treated with fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of interferon [IFN]-beta-1a (RNF).
详细描述
The objective of the study is to investigate whether RNF treatment initiated after the first clinical event versus delayed treatment results in the prolongation of time to Clinically Definite Multiple Sclerosis (CDMS) conversion up to Month 36 and up to Month 60 since randomization in Study 27025 (REFLEX). Furthermore, the study is intended to explore whether RNF treatment initiated after the first clinical event versus delayed treatment delays disability (including development of secondary progressive MS) and reduces disease activity (including the annual relapse rate [ARR]) in the long term (up to Month 36 and up to Month 60 since randomization in Study 27025 (REFLEX). The study will also assess the long-term safety profile of RNF (up to Month 36 and up to Month 60 since randomization in Study 27025 (REFLEX).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Reach scheduled end of study in Study 27025 (REFLEX) (completion of 24 months participation)
- •Medical assessment by the Investigator/treating physician from study 27025 that there is no objection to the subject's participation in this extension trial considering the medical experience from Study 27025 (REFLEX). Special attention should be given to laboratory abnormalities and clinically significant liver, renal and bone-marrow dysfunction
- •If female, subject must:
- •be neither pregnant nor breast-feeding, nor attempting to conceive
- •use a highly effective method of contraception. A highly effective method of contraception is defined as those which result in a low failure rate (that is [i.e.] less than 1 percent [%] per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner
- •Subject is willing to follow study procedures
- •Subject has given written informed consent
排除标准
- •Subject has any disease other than MS that could better explain the subject's signs and symptoms
- •Subject has a primary progressive course of MS
- •Subject has total bilirubin greater than 2.5 times upper limit of normal (ULN) at both Month 24 and at the previous visit (i.e. Month 21) (subjects with greater than 2.5 times ULN at Month 24 only are eligible for enrollment and should be managed as per label recommendations until normalization of the value)
- •Subject has total aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase (ALP) greater than 2.5 times the ULN values at both Month 24 and at the previous visit (i.e. Month 21) (subjects with greater than 2.5 times ULN at Month 24 only are eligible for enrollment and should be managed as per label recommendations until normalization of the value)
- •Subject suffers from another current autoimmune disease
- •Subject suffers from major medical or psychiatric illness (including history of, or current, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol
- •Subject has a history of seizures not adequately controlled by treatment
- •Subject has cardiac disease, such as angina, congestive heart failure or arrhythmia
- •Subject has a known allergy to IFN-beta or the excipient(s) of the study medication
- •Subject has any condition that could interfere with the MRI evaluation
- •Subject has a known allergy to gadolinium-diethylene triamine pentaacetic acid (DTPA)
- •Subject has a history of alcohol or drug abuse
- •Subject has previously participated in this study
- •Subject has moderate to severe renal impairment
- •Subject is pregnant or lactating
- •Subject has any medical, psychiatric or other conditions that compromise his/her ability to understand the subject information, to give informed consent, to comply with the study protocol, or to complete the study
研究组 & 干预措施
RNF 44 mcg thrice weekly
Active Comparator
干预措施: RNF (Drug)
RNF 44 mcg once weekly and placebo
Active Comparator
干预措施: RNF (Drug)
RNF 44 mcg once weekly and placebo
Active Comparator
干预措施: Placebo (Drug)
Placebo/RNF 44 mcg thrice weekly
Active Comparator
干预措施: RNF (Drug)
结局指标
主要结局
Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score up to 36 Months
时间窗: Baseline (Day 1 of Study 27025) up to 36 Months
CDMS was defined by the occurrence of a second attack or relapse over 36 months in participants who presented with clinically isolated syndrome (CIS) accompanied by an abnormal magnetic resonance imaging (MRI) scan. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis \[MS\]) was calculated. Time to conversion to CDMS was represented by Kaplan-Meier estimates of the cumulative percentage (%) of participants with CDMS.
次要结局
- Change From Baseline in Time Constant 1 (T1) Hypointense Lesion Volume and Time Constant 2 (T2) Lesion Volume at Month 36(Baseline (Day 1 of Study 27025), Month 36)
- Percent Change From Baseline in Brain Volume at Month 36(Baseline (Day 1 of Study 27025), Month 36)
- Percentage of Participants With Conversion to McDonald Multiple Sclerosis (MS) up to 36 Months(Baseline (Day 1 of Study 27025) up to CDMS conversion and/or up to 36 Months)
- Time to Confirmed Expanded Disability Status Scale (EDSS) Progression up to 36 Months(Baseline (Day 1 of Study 27025) up to 36 Months)
- Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, New Gadolinium Enhanced (Gd+) Lesions and New Time Constant 1 (T1) Lesions Per Participant Per Scan at Month 36(Month 36)
- Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Month 36(Baseline (Day 1 of Study 27025), Month 36)
- Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, New Gadolinium Enhanced (Gd+) Lesions and New T1 Lesions Per Participant Per Scan at Month 60(Month 60)
- Change From Baseline in Time Constant 1 (T1) Hypointense Volume, and Time Constant 2 (T2) Lesion Volume at Month 60(Baseline (Day 1 of Study 27025), Month 60)
- Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score up to Month 60(Baseline (Day 1 of Study 27025) up to 60 Months)
- Percentage of Relapse-Free Participants at Month 60(Month 60)
- Change From Baseline in Paced Auditory Serial Addition Test 3 (PASAT-3) Score at Month 36(Baseline (Day of Study 27025), Month 36)
- Percentage of Relapse-Free Participants at Month 36(Month 36)
- Numbers of Participants With Binding Antibodies (BAb) and Neutralizing Antibody (NAb) at Month 36(Month 36)
- Percent Change From Baseline in Brain Volume at Month 60(Baseline (Day 1 of Study 27025), Month 60)
- Numbers of Participants With Binding Antibodies (BAb) and Neutralizing Antibody (NAb) at Month 60(Month 60)
- Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 36(Baseline (Day of Study 27025), Month 36)
- Time to Confirmed Expanded Disability Status Scale (EDSS) Progression up to 60 Months(Baseline (Day 1 of Study 27025) up to 60 Months)
- Percentage of Participants With Conversion to McDonald Multiple Sclerosis (MS) at Month 60(Month 60)
- Change From Baseline in Paced Auditory Serial Addition Test 3 (PASAT-3) Score at Month 60(Baseline (Day 1 of Study 27025), Month 60)
- Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 60(Baseline (Day 1 of Study 27025), Month 60)
- Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Month 60(Baseline (Day 1 of Study 27025), Month 60)
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation(Month 24 up to Month 60)
研究者
研究点 (2)
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