An Open-Label, Randomized, Multicenter, Active-Controlled, Parallel-Group Study to Evaluate the Safety, Tolerability, and Efficacy of BIIB017 in Pediatric Subjects Aged 10 to Less Than 18 Years for the Treatment of Relapsing-Remitting Multiple Sclerosis, With Optional Open-Label Extension
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Biogen
- 入组人数
- 152
- 试验地点
- 65
- 主要终点
- Part 1: Annualized Relapse Rate (ARR) at Week 48
研究概览
简要总结
This study will evaluate the safety, tolerability, and descriptive efficacy of BIIB017 in pediatric participants with relapsing-remitting multiple sclerosis (RRMS) and to assess the pharmacokinetics (PK) of BIIB017 in pediatric participants with RRMS in Part 1. In Part 2, the study will evaluate the long-term safety of BIIB017 and further describe safety and the long-term multiple sclerosis (MS) outcomes after BIIB017 treatment in participants who completed the study treatment at Week 96 in Part 1 of the study.
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 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have a diagnosis of RRMS as defined by the revised consensus definition for pediatric MS.
- •Must have an EDSS score between 0.0 and 5.
- •Must have experienced >= 1 relapse in the 12 months prior to randomization (Day 1) or >= 2 relapses in the 24 months prior to randomization (Day 1) or have evidence of asymptomatic disease activity (Gd-enhancing lesions) on brain MRI in the 6 months prior to randomization (Day 1).
- •Participants who completed the study treatment in Part 1 (Week 96 Visit), as per protocol.
排除标准
- •Primary progressive, secondary progressive, or progressive relapsing MS. 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 participants by the lack of clinically stable periods or clinical improvement.
- •History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
- •Known allergy to any component of Avonex or BIIB017 formulation.
- •Occurrence of an MS relapse that has occurred within 30 days prior to randomization (Day 1) and/or the participant has not stabilized from a previous relapse prior to randomization (Day 1).
- •Any previous treatment with PEGylated human IFN β-1a.
- •Any significant changes in medical history occurring after enrollment in Part 1, including laboratory test abnormalities or current clinically significant conditions that, in the opinion of the Investigator, would have excluded the participant's participation in Part
- •The Investigator must re-assess the participant's medical fitness for participation and consider any factors that would preclude treatment.
- •The participant could not tolerate BIIB017 in Part
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
BIIB017 (peginterferon beta-1a)
Participants will receive subcutaneous (SC) injection of BIIB017 (peginterferon beta-1a) 63 microgram (μg) on Day 1, followed by 94 μg at Week 2, followed by 125 μg at Week 4, and then 125 μg SC injection every 2 weeks up to Week 96 in Part 1 of the study. Eligible participants who enter optional Part 2 of the study will receive 125 μg SC injections of BIIB017 every 2 weeks for 96 Weeks.
干预措施: BIIB017 (peginterferon beta-1a) (Drug)
Avonex
Participants will receive Avonex (interferon beta type 1a) starting at a dose of 7.5 μg on Day 1, followed by an increase of 7.5 μg each week for 3 weeks, followed by 30 μg intramuscular (IM) injections every week up to Week 96 in Part 1 of the study. Eligible participants who enter optional Part 2 of the study will receive 125 μg SC injections of BIIB017 every 2 weeks for 96 Weeks.
干预措施: Interferon beta type 1a (Drug)
结局指标
主要结局
Part 1: Annualized Relapse Rate (ARR) at Week 48
时间窗: Week 48
A multiple sclerosis (MS) relapse is defined as the onset of new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings. ARR is calculated as the total number of relapses in each treatment group adjusted for the duration of study treatment in person-years.
Part 2: Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Treatment Discontinuation
时间窗: From Week 96 to Week 196
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, or is a medically important event.
次要结局
- Part 1: Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans at Weeks 24, 48, and 96(Weeks 24, 48, and 96)
- Part 1: Time to First Relapse(Up to Week 96)
- Part 1: ARR at Week 96(Week 96)
- Part 1: Percentage of Participants Free of New MRI Activity in the Brain (Free of Gadolinium [Gd]-Enhancing Lesions and New or Newly Enlarging T2 Hyperintense Lesions) at Weeks 24, 48, and 96(Weeks 24, 48, and 96)
- Part 1: Percentage of Participants Free of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans at Weeks 24, 48, and 96(Weeks 24, 48, and 96)
- Part 1: Change from Baseline in Height at Weeks 24, 48, 72, 96, and 100(Baseline, Weeks 24, 48, 72, 96, and 100)
- Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady State for BIIB017(Within 8 hours postdose on Day 1 of Week 1; Within 8 hours, 48 and 120 hours postdose on Day 1 of Week 4; Within 8 hours postdose on Day 1 of Week 24)
- Part 1: Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Treatment Discontinuation(Up to Week 100)
- Part 1: Change from Baseline in Pulse Rate at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100(Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100)
- Part 1: Number of Gd-Enhancing Lesions on Brain MRI Scans at Weeks 24, 48, and 96(Weeks 24, 48, and 96)
- Part 1: Percentage of Participants Free of Relapse at Weeks 48 and 96(Weeks 48 and 96)
- Part 1: Change from Baseline in the Quality of Life as Measured by the Pediatric Quality of Life Inventory (PedsQL) at Weeks 24, 48, 72 and 96(Baseline, Weeks 24, 48, 72 and 96)
- Part 1: Maximum Observed Plasma Concentration (Cmax) at Steady State for BIIB017(Within 8 hours postdose on Day 1 of Week 1; Within 8 hours, 48 and 120 hours postdose on Day 1 of Week 4; Within 8 hours postdose on Day 1 of Week 24)
- Part 1: Number of Participants With Binding and Neutralizing Antibodies to Interferon Beta Type 1a (IFN β-1a) [All Participants](Up to Week 96)
- Part 1: Change from Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Weeks 48, 96, and 100(Baseline (Before dosing), Weeks 48, 96, and 100)
- Part 1: Percentage of Participants with Changes Over Time in Clinical Laboratory Values(Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100)
- Part 2: Change from Baseline in Height at Weeks 120, 144, 168, 192, and 196(Baseline (Week 96), Weeks 120, 144, 168, 192, and 196)
- Part 2: Change from Baseline in Weight at Weeks 120, 144, 168, 192, and 196(Baseline (Week 96), Weeks 120, 144, 168, 192, and 196)
- Part 2: Change from Baseline in Tanner Score at Weeks 120, 144, 168, 192, and 196(Baseline (Week 96), Weeks 120, 144, 168, 192, and 196)
- Part 2: Number of Participants With Binding Antibodies to PEG (BIIB017-Treated Participants)(Up to Week 192)
- Part 2: Change from Baseline in Body Temperature at Weeks 120, 144, 168, 192, and 196(Baseline (Week 96), Weeks 120, 144, 168, 192, and 196)
- Part 2: Percentage of Participants with Changes Over Time in Clinical Laboratory Values(Baseline (Week 96), Weeks 108, 120, 132, 144, 156, 168, 180, 192, and 196)
- Part 1: Change from Baseline in Cognition at Weeks 24, 48, 72, and 96 as Measured by the Symbol Digit Modality Test (SDMT)(Baseline, Weeks 24, 48, 72, and 96)
- Part 1: Change from Baseline in Weight at Weeks 24, 48, 72, 96, and 100(Baseline, Weeks 24, 48, 72, 96, and 100)
- Part 1: Change from Baseline in Tanner Score at Weeks 24, 48, 72, 96, and 100(Baseline, Weeks 24, 48, 72, 96, and 100)
- Part 1: Number of Participants With Binding Antibodies to Peginterferon (PEG) [BIIB017-Treated Participants](Up to Week 96)
- Part 1: Change from Baseline in Blood Pressure at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100(Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100)
- Part 1: Change from Baseline in Body Temperature at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100(Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100)
- Part 2: Change from Baseline in EDSS Score at Weeks 120, 144, 168, 192, and 196(Baseline (Week 96), Weeks 120, 144, 168, 192, and 196)
- Part 2: Change from Baseline in Pulse Rate at Weeks 120, 144, 168, 192, and 196(Baseline (Week 96), Weeks 120, 144, 168, 192, and 196)
- Part 1: Change from Baseline in the Expanded Disability Status Scale (EDSS) Score at Weeks 48 and 96(Baseline, Weeks 48, and 96)
- Part 1: Area Under the Plasma Concentration-Time Curve from Time Zero to End of Dosing Interval (AUCtau) for BIIB017(Within 8 hours postdose on Day 1 of Week 1; Within 8 hours, 48 and 120 hours postdose on Day 1 of Week 4; Within 8 hours postdose on Day 1 of Week 24)
- Part 1: Change from Baseline in Depression as Assessed by Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) at Weeks 12, 24, 36, 48, 60, 72, 84, 96, and 100(Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, and 100)
- Part 2: ARR at Weeks 144 and 192(Weeks 144 and 192)
- Part 1: Change from Baseline in Respiratory Rate at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100(Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100)
- Part 2: Change from Baseline in Blood Pressure at Weeks 120,144,168, 192, and 196(Baseline (Week 96), Weeks 120, 144, 168, 192, and 196)
- Part 2: Change from Baseline in Respiratory Rate at Weeks 120, 144, 168, 192, and 196(Baseline (Week 96), Weeks 120, 144, 168, 192, and 196)
- Part 2: Change from Baseline in 12-Lead ECG Parameters at Weeks 144, 192, and 196(Baseline (Week 96), Weeks 144, 192, and 196)
- Part 2: Number of Participants With Binding and Neutralizing Antibodies to IFN β-1a (All Participants)(Up to Week 192)
- Part 2: Change from Baseline in Depression as Assessed by Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) at Weeks 108, 120, 132, 144,156, 168, 180, 192, and 196(Baseline (Week 96), Weeks 108, 120, 132, 144,156, 168, 180, 192, and 196)