A phase 3, multicenter, double-blind, randomized, placebo controlled, parallel-group study to evaluate the safety and efficacy of NU100 in patients with relapsing forms of multiple sclerosis
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 500
- 试验地点
- 12
- 主要终点
- To evaluate the safety and efficacy of NU100 in patients with relapsing remitting multiple sclerosis (RRMS) as compared to placebo and an active comparator.
研究概览
简要总结
The primary objective of this study is:
To evaluate the safety and efficacy of NU100 in patients with relapsing remitting multiple sclerosis (RRMS) as compared to placebo and an active comparator.
The primary clinical objective selected for this Phase 3 study, the cumulative number of new combined unique active lesions (CALs; defined as new gadolinium T1-weighted lesions and non��’enhancing new and newly enlarging T2-weighted lesions) on magnetic resonance imaging (MRI) scans over the course of 4 and 12 months of treatment to demonstrate the superiority of NU100 to placebo and the non-inferiority of NU100 to Betaferon®, respectively.
The study will include 3 treatment arms (NU100, Betaferon, and placebo) with 2 cohorts (7 and 5 MRIs) within each arm. Five hundred patients will be randomized to 1 of the following treatments in a 2:9:2:9:2:1 ratio:
· Group A Cohort 1 (n=40): NU100 0.25 mg by subcutaneous (SQ) injection, every other day (e.o.d.) for 12 months
· Group A Cohort 2 (n=180): NU100 0.25 mg SQ, e.o.d. for 12 months
· Group B Cohort 1 (n=40): Betaferon 0.25 mg SQ, e.o.d. for 12 months
· Group B Cohort 2 (n=180): Betaferon 0.25 mg SQ, e.o.d. for 12 months
· Group C Cohort 1 (n=40): Placebo SQ, e.o.d. for 4 months then NU100 0.25 mg SQ, e.o.d. for 8 months
Group C Cohort 2 (n=20): Placebo SQ, e.o.d. for 4 months then NU100 0.25 mg SQ, e.o.d. for 8 months
Within each arm patients are randomized to one of 2 MRI cohorts. Patients randomized to Cohort 1 undergo 7 MRIs (at screening and Months 2, 3, 4, 6, 9, and 12). Patients randomized to Cohort 2 undergo 5 MRIs (at screening and Months 3, 6, 9, and 12).
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 60.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Female or male patients, aged between 18 and 60 years, inclusive 2.Signed and dated statement of informed consent 3.Diagnosis of RRMS according to McDonald’s Criteria – revision 2010 (Polman et al., 2011) 4.Interferon (IFN) beta-1b naïve 5.Expanded Disability Status Scale (EDSS) score of < 5.5 6.At least 1 documented relapse in the past year (defined as the appearance of a new clinical sign/symptom [one that had been stable for at least 30 days] that persisted for a minimum of 24 hours in the absence of fever) ---or--- a subclinical sign/symptom (defined as a Gd enhancing lesion or a new T2 lesion demonstrated on MRI examination on a prior MRI that has been completed within 1 year of the screening MRI).
- •The Screening (V-1) MRI should not be used for this determination.
- •7.No relapse in the 4 weeks prior to the screening visit (V-1).
- •8.Must be in a clinically stable or improving neurological state 4 weeks preceding the screening visit (V-1).
排除标准
- •1.Relapse at the baseline visit (V0) or occurring within 4 weeks prior to the screening visit (V-1) 2.Intake of glatiramer acetate within 3 months prior to the screening (V-1) visit 3.Intake of previous immunotherapy or immunosuppressant treatment, within 4 months prior to the screening (V-1) visit 4.Intake of or previously received therapy with cladribine or alemtuzumab 5.An active viral, bacterial, or systemic fungal infection within 1 week of baseline (V0) 6.Use of systemic steroids within 3 weeks prior to the screening (V-1) MRI 7.Progressive disease 8.Level of liver enzymes 2.5 x the upper limit of normal 9.Abnormal renal function (estimated Glomerular Filtration Rate [eGFR] 60 ml/min/1.73 m2 ) 10.Positive serology or history for Hepatitis B, C, or human immunodeficiency virus (HIV) 11.Serious or acute coronary diseases, defined by at least 1 of the following conditions: a.Clinical symptoms of ischemic heart disease b.ST elevation or depression 2 mm on the electrocardiogram (ECG) c.Clinical symptoms of cardiac failure and/or current medical treatment for cardiac failure d.Severe ventricular arrhythmia (frequent premature ventricular beats) e.Atrioventricular block at third level 12.Chronic use of non-steroidal anti-inflammatory drugs 13.History of any of the following: a.Severe depression or suicide attempt b.Uncontrolled seizure disorder c.Cancer, excluding adequately treated basal cell carcinoma of the skin or adequately treated in situ carcinoma of the cervix d.Previous contrast reaction to gadolinium or any other contraindications to MRI (e.g., metal in the eye, pacemakers, aneurysm clip) 14.Allergy to human albumin or to mannitol 15.Excessive alcohol use or illicit drug use 16.Women who are breast feeding, pregnant, or planning to become pregnant, or are unwilling to use an effective birth control method while on study 17.Medical, psychiatric, or other conditions that compromise the patients ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study 18.Participation in any other study involving investigational or marketed products, concomitantly or within 30 days prior to entry in the study Current participation in other clinical trials.
结局指标
主要结局
To evaluate the safety and efficacy of NU100 in patients with relapsing remitting multiple sclerosis (RRMS) as compared to placebo and an active comparator.
时间窗: The cumulative number of new combined unique active lesions (CALs; defined as new gadolinium T1-weighted lesions and non enhancing new and newly enlarging T2-weighted lesions) on magnetic resonance imaging (MRI) scans over the course of 4 and 12 months of treatment to demonstrate the superiority of NU100 to placebo and the non-inferiority of NU100 to Betaferon®, respectively.
次要结局
- The rates of reduction for a non-inferiority trial require several assumptions: an expected difference between the 2 active therapies, a tolerable difference and the variation found in the treatment groups along with Type I and Type II errors. If we assume that the 2 drugs are truly equivalent, then our expected difference is zero.(Incidence of annualized relapse rates)