A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Trial of Rebif New Formulation (44 Microgram [Mcg] Three Times Weekly [Tiw] and 44 Mcg Once Weekly [ow]) in Subjects at High Risk of Converting to Multiple Sclerosis (REFLEX)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 517
- 试验地点
- 1
- 主要终点
- Time to Conversion to Multiple Sclerosis (MS) According to the McDonald Criteria (2005)
研究概览
简要总结
The study is a 24 months randomized, double-blind, Placebo-controlled, multi-center clinical trial with an optional 12 months open label extension.
The primary objective of the study is to evaluate the effect of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN] beta-1a (RNF) 44 microgram (three times weekly and once weekly) versus placebo on the time to conversion to McDonald multiple sclerosis (MS) criteria (2005) in subjects with a first clinical demyelinating event at high risk of converting to MS.
The main secondary objective of study is to evaluate the effect of RNF 44 microgram (three times weekly and once weekly) versus placebo on the "Time to conversion to clinically definite MS (CDMS)" in subjects with a first clinical demyelinating event at high risk of converting to MS.
At the end of 24 month double-blind core REFLEX trial, subjects who will not convert to CDMS and decide to receive open-label (OL) treatment will be enrolled into an open-label, 12 month extension period to evaluate the effect of RNF 44 mcg three times weekly treatment on the time to conversion to McDonald MS and time to conversion to CDMS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Single, first clinical event suggestive of MS within 60 days prior to study Day 1, which is the day of randomization (clock starts 24 hours after onset). The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic, other than a paresthesia, vegetative or cerebral dysfunction
- •At least two clinically silent lesions on the T2-weighted MRI scan, with a size of at least 3 millimeter (mm), at least one of which is ovoid or periventricular or infratentorial
- •EDSS 0 - 5.0 at least one time point during the screening period before start of treatment
- •18 and 50 years old, inclusive
- •Willing to follow study procedures
- •Written informed consent
- •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 vasectomised partner
排除标准
- •Diagnosis of MS (per McDonald criteria 2005)
- •Any other disease that could better explain the subject's signs and symptoms
- •Complete transverse myelitis or bilateral optic neuritis
- •Subject uses or has used any other approved MS disease-modifying drug (DMD)
- •Any investigational drug or undergone an experimental procedure within 12 weeks prior to study Day 1
- •Oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 30 days prior to study Day 1
- •Total bilirubin greater than 2.5 times upper limit of normal (ULN)
- •Subject has total aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase (ALP) greater than 2.5 times the ULN
- •Inadequate bone marrow reserve, defined as a total white blood cell count less than 3.0 x 109 per liter (/L), platelet count less than 75 x 109/L, hemoglobin less than 100 gram per liter (g/L)
- •Current autoimmune disease
- •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
- •History of seizures not adequately controlled by treatment
- •Cardiac disease, such as angina, congestive heart failure or arrhythmia
- •Known allergy to IFN-beta or the excipient(s) of the study medication
- •Any condition that could interfere with the MRI evaluation;
- •Known allergy to gadolinium-diethylene triamine pentaacetic acid (DTPA)
- •Previously participated in this study
- •Participated in any clinical trial within the past 6 months
- •Any immunomodulatory or immunosuppressive therapy at any time prior to enrollment, including, but not limited to, the following products: any IFN, glatiramer acetate (Copolymer I), cyclophosphamide, cyclosporine, methotrexate, linomide, azathioprine, mitoxantrone, teriflunomide, laquinimod, cladribine, total lymphoid irradiation, anti-lymphocyte monoclonal antibody treatment (e.g. natalizumab, alemtuzumab/Campath, anti-cluster of differentiation 4 [CD4]), intravenous, immunoglobulins (Igs), cytokines or anti-cytokine therapy
- •Any experimental MS treatment prior to trial entry, including, but not limited to, any statins (if given to prevent MS) and pentoxyfylline
- •History of alcohol or drug abuse
- •Intolerance or any contraindication to both paracetamol (acetaminophen) and ibuprofen
- •Inability to administer subcutaneous injections either by self or by caregiver
- •Moderate to severe renal impairment
研究组 & 干预措施
RNF 44 mcg once weekly and placebo twice weekly for blinding
干预措施: Placebo (Drug)
RNF 44 mcg three times weekly
干预措施: RNF (Drug)
RNF 44 mcg once weekly and placebo twice weekly for blinding
干预措施: RNF (Drug)
Placebo three times weekly
干预措施: Placebo (Drug)
结局指标
主要结局
Time to Conversion to Multiple Sclerosis (MS) According to the McDonald Criteria (2005)
时间窗: Various time points from randomization up to 36 months
The McDonald criteria use dissemination in time and space established by MRI findings to provide a clinical diagnosis for MS. Dissemination in time is established by a T2 or Gd+ lesion found on a repeat MRI. Dissemination in space is established by the presence of any 3 of the following: 1 Gd+ lesion or 9 T2 bright lesions if there is no enhancement; greater than or equal to 1 infratentorial lesion; greater than or equal to 1 juxtacortical lesion; greater than or equal to 3 periventricular lesions.
次要结局
- Change From Baseline in Expanded Disability Status Score (EDSS) Score at Month 36(Baseline, Month 36)
- Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a 3-Month Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score(Various time points from randomization up to 36 months)
- Mean Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, Gadolinium Enhanced (Gd+) Lesions and New Time Constant 1 (T1) Hypointense Lesions Per Participant Per Scan(Month 24 up to Month 36)
- Change From Baseline in Time Constant 2 (T2) Lesion Volume , Time Constant 1 (T1) Hypointense Lesion Volume and Gadolinium Enhanced (Gd+) Lesion Volume at Month 36(Baseline, Month 36)