A Multi-centre, Double Blind, Randomized, Placebo Controlled, Parallel Group Trial Investigating Minocycline Versus Placebo as Add-on Therapy in Patients Who Are on Treatment With Interferon-beta-1a 44 Mcg Tiw (Rebif®) for the Treatment of Relapsing-Remitting Multiple Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 305
- 试验地点
- 1
- 主要终点
- Number of Participants Who Experienced First Documented Relapse
研究概览
简要总结
This is a multicentric, double-blind, placebo-controlled, randomized, parallel group study to estimate the effect of minocycline as add-on to interferon beta-1a (IFN beta-1a) in subjects with relapsing-remitting multiple sclerosis (RRMS).
详细描述
Interferon beta-1a is the approved standard therapy in RRMS. The beneficial effects of minocycline in the experimental autoimmune encephalomyelitis (EAE) model and its possible inhibitory effect on the degradation of IFN beta-1a suggest that minocycline treatment may have beneficial effects in MS as add-on therapy in subjects who are on treatment with IFN beta-1a. Adjuvant treatment with minocycline is easy to administer, well tolerated and relatively inexpensive. This is a multicentric, double blind, placebo controlled, randomized, parallel group study. Eligible subjects already started with IFN beta-1a (Rebif®) will be randomized 1:1 for treatment with either minocycline 2*100 mg daily as add-on therapy or placebo. The subjects will be examined clinically at baseline and after 12, 24, 48, 72 and 96 weeks. Laboratory tests (hematology and clinical chemistry) will be performed at baseline and after 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96 weeks (at 4, 8, 36, 60 and 84 weeks only an additional liver enzyme test will be scheduled). The MRI (T1-weighted and T2-weighted) before treatment and after 96 weeks and immunological studies before treatment and after 48 weeks will be performed in a limited number of subjects in selected centers.
OBJECTIVES
Primary Objective:
The effect of minocycline versus placebo in subjects receiving treatment with IFN beta-1a on the time to the first documented relapse
Secondary Objectives:
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
- •Subjects who have given written informed consent prior to any trial related activities. Trial related activities are any procedures that would not have been performed during normal management of the subject
- •Subjects with stable disease without relapses in the last 30 days
- •Subjects aged between 18 and 55 years (both included)
- •Subjects who suffer from definite RRMS according to Poser criteria (clinical definite multiple sclerosis [CDMS] or laboratory supported definite multiple sclerosis [LSDMS]) or definite MS according to McDonald criteria
- •Subjects who have started treatment with Rebif® 44 mcg 3 months ago (+/- 1 month) including the titration phase
- •Subjects who have a disability equivalent to an EDSS of 5.5 or less
- •Subjects who have shown clinical activity defined as at least 1 documented relapse within the last year (A documented relapse is defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, persisting for more than 48 hours and with a previous period for more than 30 days with a stable or an improving condition. The exacerbation must be equivalent to an increase of at least 1 point in 2 functional systems or to an increase of 2 points in 1 system, either in the pyramidal, cerebellar, brain-stem, sensory, bowel and bladder, visual, cerebral or other functional system or an increase of at least half a point on the EDSS. Changes in bowel and bladder or cerebral functions should not solely be responsible for documentation of a relapse. The relapses must have been evaluated by a neurologist, retrospectively if necessary)
- •Subjects must be prepared to and considered able to follow the protocol during the whole trial period and to attend the planned visits, even if the treatment has to be withdrawn
- •Female subjects must either: be post-menopausal or surgically sterilized; or use a hormonal contraceptive or intra-uterine device (only following contraceptives are allowed: birth control pills, intra-uterine device, depot injection of gestagen, subdermal implant, hormonal vaginal ring and transdermal depot patches); or be sexually inactive for the duration of the study, and be neither pregnant nor breast-feeding (confirmation that the subject is not pregnant must be established by a negative serum human chorionic gonadotropin (hCG) pregnancy test within 28 days of Study Day 1 and a negative urine pregnancy test on Study Day
- •A pregnancy test is not required if the subject is post-menopausal or surgically sterilized)
排除标准
- •Subjects with any condition that might give rise to similar symptoms as MS
- •Subjects who have received any other immunomodulatory or immunosuppressive treatment 6 months prior to inclusion into the trial (the obligatory pre-study 3 months [+/- 1 month] period of Rebif® treatment not included)
- •Subjects who have received mitoxantrone or total lymphoid radiation at any time
- •Subjects who have received treatment with glucocorticoids or adrenocorticotropic hormone (ACTH) later than 1 month prior to inclusion into the trial
- •Subjects who have experienced a relapse within 1 month prior to inclusion into the trial
- •Subjects who have suffered from major depression
- •Subjects with alcohol or drug dependency
- •Subjects with cardiac insufficiency, cardiomyopathy, significant cardiac dysrhythmias, unstable or advanced ischemic heart disease (New York Heart Association [NYHA] grade III or IV), or significant hypertension (Blood Pressure > 180/110 millimeter of mercury [mmHg])
- •Subjects with renal insufficiency defined as serum creatinine > 1.5 times the upper normal reference limit
- •Subjects with alanine aminotransferase (ALAT) and asparagine aminotransferase (ASAT) (or either 1 if only 1 of the 2 is measured) levels more than 2 times the normal upper reference limit.
- •Subjects with leucopoenia < 2500 per microliter (microL) or thrombopenia < 100000 per microL
- •Subjects with any medical illness requiring treatment with systemic corticosteroids
- •Subjects with any systemic disease that can influence the subject's safety and compliance, or the evaluation of the disability
- •Female subjects who are pregnant or breastfeeding or who plan to become pregnant during the study
- •Subjects with known or suspected allergy to minocycline or other tetracyclines
- •Subjects who have participated in any other studies, involving other investigational products, within 30 days prior to participating in this trial
研究组 & 干预措施
Minocycline group
干预措施: Minocycline (Drug)
Placebo Group
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants Who Experienced First Documented Relapse
时间窗: Baseline up to 96 weeks (+/- 1 week) or early termination (ET)
Documented relapse: development of new/exacerbation of existing neurological symptoms, persisting for \>48 hrs and with previous period for \>30 days with stable/improving condition. Exacerbation = at least (\>=)1 point increase in 2 functional systems/2 points increase in 1 system,either in pyramidal, cerebral, brain-stem, sensory, bowel and bladder, visual, cerebral or other functional system or \>=0.5 point increase on expanded disability status scale (EDSS) which assesses disability in 8 functional systems with overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis \[MS\]).
次要结局
- Number of Participants With Documented Relapses(Baseline up to 96 weeks (+/- 1 week) or ET)
- Number of New or Enlarging Lesions on Time Constant 2 (T2) Weighted Magnetic Resonance Imaging (MRI)(Final visit (96 weeks [+/- 1 week]) or ET)
- Changes in Brain Volume Measured on Magnetic Resonance Imaging (MRI)(Screening , final visit (96 weeks [+/- 1 week]) or ET)