Open-Label, Randomized, Multicenter, Multiple-Dose, Active-Controlled, Parallel-Group, Efficacy and Safety Study of BG00012 in Children From 10 to Less Than 18 Years of Age With Relapsing-Remitting Multiple Sclerosis, With Optional Open-Label Extension
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 156
- 试验地点
- 62
- 主要终点
- Part 1: Proportion of Participants Free of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans
研究概览
简要总结
The main objectives of Part 1 are as follows: To evaluate the safety, tolerability, and efficacy of BG00012 in pediatric participants with RRMS, as compared with a disease-modifying treatment and to assess health outcomes and evolution of disability. The primary objective of Part 2 is to evaluate the long-term safety of BG00012 in participants who completed Week 96 in Part 1 of Study 109MS306. The secondary objective of Part 2 is to describe the long-term MS outcomes of BG00012 in participants who completed Week 96 in Part 1 of Study 109MS306.
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
- None
入排标准
- 年龄范围
- 10 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females aged from 10 to less than 18 years old at the time of informed consent or assent.
- •Must have a body weight of ≥30 kg.
- •Must have a diagnosis of RRMS (consensus definition for pediatric RRMS [Krupp 2013]).
- •Must be ambulatory with a baseline EDSS score between 0 and 5.5, inclusive.
- •Must have experienced at least 1 of the following 3 conditions: a) at least 1 relapse within the last 12 months prior to Day 1 with a prior brain MRI demonstrating lesions consistent with MS; b) at least 2 relapses within the last 24 months prior to Day 1, with a prior brain MRI demonstrating lesions consistent with MS; c) evidence of Gd-enhancing lesions of the brain on an MRI performed within the 6 weeks prior to Day
- •Must be neurologically stable, with no evidence of relapse within 50 days prior to Day 1 and no evidence of corticosteroid treatment within 30 days prior to Day
- •Participants of childbearing potential who are sexually active must be willing to practice effective contraception during the study and be willing and able to continue contraception for at least 30 days after their final dose of study treatment.
排除标准
- •Primary progressive, secondary progressive, or progressive relapsing MS (as defined by [Lublin and Reingold 1996]). These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Participants with these conditions may also have superimposed relapses but are distinguished from relapsing-remitting participants by the lack of clinically stable periods or clinical improvement.
- •Disorders mimicking MS, such as other demyelinating disorders (e.g., acute disseminated encephalomyelitis), systemic autoimmune disorders (e.g., Sjögren disease, lupus erythematosus), metabolic disorders (e.g., dystrophies), and infectious disorders.
- •History of premalignant or malignant disease. Participants with basal cell carcinoma that has been completely excised prior to screening will remain eligible.
- •History of severe allergic or anaphylactic reactions, or known drug hypersensitivity to DMF, fumaric acid esters, or interferon beta-1a (IFN Beta-1a).
- •History of abnormal laboratory results indicative of any significant endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, renal, and/or any other major disease that would preclude participation in a clinical study.
- •History of clinically significant cardiovascular, pulmonary, GI, dermatologic, growth, developmental, psychiatric (including depression), neurologic (other than MS), and/or other major disease that would preclude participation in a clinical study.
- •History of human immunodeficiency virus.
- •An MS relapse that has occurred within 50 days prior to Day 1 AND/OR the participant has not stabilized from a previous relapse prior to Day
- •Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the participant unsuitable for enrollment.
- •NOTE: Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
IFN β-1a (Avonex)
Participants will receive the recommended dose of 30 μg (weekly)
干预措施: Interferon β-1a (Drug)
BG00012
Participants will receive the recommended dose of 240 mg orally, twice a day
干预措施: dimethyl fumarate (Drug)
结局指标
主要结局
Part 1: Proportion of Participants Free of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans
时间窗: At Week 96
Participants who were free of new or newly enlarging T2 hyperintense lesions were assessed on Brain MRI scans.
Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
时间窗: From Week 96 up to last follow-up visit (up to Week 340)
An adverse event (AE) was any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE was any untoward medical occurrence that at any dose resulted in death, in the view of the Investigator, placed the participant at immediate risk of death, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. TEAEs were defined as AEs occurring or worsening after beginning study treatment (after the first dose).
Part 2: Number of Participants Who Discontinued Study Treatment Due to an AE
时间窗: From Week 96 up to last follow-up visit (up to Week 340)
An AE was any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
次要结局
- Part 2: Change From Baseline in Weight(Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340)
- Part 1: Number of New or Newly Enlarged T2 Hyperintense Lesions on Brain MRI Scans(At Weeks 24 and Week 96)
- Part 1: Proportion of Participants Free of New or Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans(At Weeks 24 and 48)
- Part 1: Proportion of Participants Free of New MRI Activity as Measured by Brain MRI Scans(At Weeks 24, 48, and 96)
- Part 1: Time to First Relapse(Up to Week 96)
- Part 1: Proportion of Relapse-Free Participants(Up to Week 96)
- Part 1: Annualized Relapse Rate (ARR)(At Weeks 48 and 96)
- Part 1: Number of Participants With TEAEs and TESAEs(From Day 1 up to Week 96)
- Part 1: Change From Baseline in Vital Signs (Temperature)(Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96)
- Part 1: Change From Baseline in Vital Signs (Pulse Rate)(Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96)
- Part 1: Change From Baseline in Vital Signs (Blood Pressure)(Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96)
- Part 1: Change From Baseline in Vital Signs (Respiratory Rate)(Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96)
- Part 1: Number of Participants With Shifts From Baseline in Electrocardiograms (ECG) Abnormalities(Up to Week 96)
- Part 1: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters)(Baseline up to Week 96)
- Part 1: Change From Baseline in Coagulation Parameters [Activated Partial Thromboplastin Time (aPTT)](Baseline, Weeks 24, 48 and 96)
- Part 1: Change From Baseline in Coagulation Parameters [Prothrombin Time (PT)](Baseline, Weeks 24, 48 and 96)
- Part 1: Change From Baseline in Coagulation Parameters [International Normalized Ratio (INR)](Baseline, Weeks 24, 48 and 96)
- Part 1: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters)(Baseline up to Week 96)
- Part 1: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Urinalysis Parameters)(Baseline up to Week 96)
- Part 1: Fatigue Score Measured by the Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale(Up to Week 96)
- Part 1: Quality of Life (QOL) as Measured by the PedsQL(Up to Week 96)
- Part 1: Change From Baseline in the Expanded Disability Status Scale (EDSS) Score(Baseline, Week 96)
- Part 2: Annualized Relapse Rate (ARR)(From Baseline (Week 96) up to Week 336)
- Part 2: Change From Baseline in the Expanded Disability Status Scale (EDSS) Score(Baseline (Week 96), Week 336)
- Part 2: Change From Baseline in Brief Visuospatial Memory Test - Revised (BVMT-R) Score(Baseline (Week 96), Weeks 144,192, 240, 288 and 336)
- Part 2: Change From Baseline in Vital Signs (Respiratory Rate)(Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340)
- Part 2: Change From Baseline in Symbol Digit Modalities Test (SDMT) Score(Baseline (Week 96), Weeks 144,192, 240, 288 and 336)
- Part 2: Number of Male Participants by Tanner Stage Assessment(At Weeks 96, 144, 192, 240, 288 and 336)
- Part 2: Number of Participants With or Without School Progression(At Weeks 144, 192, 240, 288 and 336)
- Part 2: Change From Baseline in Vital Signs (Temperature)(Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340)
- Part 2: Change From Baseline in Vital Signs (Pulse Rate)(Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340)
- Part 2: Change From Baseline in Vital Signs (Blood Pressure)(Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340)
- Part 2: Number of Participants With Shifts From Baseline in ECG Abnormalities(From Baseline (Week 96) to Week 336)
- Part 2: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters)(Baseline (Week 96) up to Week 340)
- Part 2: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters)(Baseline (Week 96) up to Week 340)
- Part 2: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Urinalysis Parameters)(Baseline up to Week 340)
- Part 2: Change From Baseline in Height(Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340)
- Part 2: Change From Baseline in Bone Age(Baseline (Week 96), Weeks 144, 192 and 240)
- Part 2: Number of Female Participants by Tanner Stage Assessment(At Weeks 96, 144, 192, 240, 288 and 336)