A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study, With an Active-Treatment Dose-Blinded Period, to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Subjects With Parkinson's Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Biogen
- 入组人数
- 357
- 试验地点
- 52
- 主要终点
- Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52
研究概览
简要总结
The primary objective of the study is to evaluate the clinical efficacy of BIIB054 via dose response using the change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score.
The secondary objectives of the study are to evaluate the dose-related safety of BIIB054, to evaluate the clinical efficacy of BIIB054 via MDS-UPDRS total score, to assess the pharmacokinetic (PK) profile of BIIB054, to evaluate the clinical efficacy of BIIB054 based on MDS-UPDRS subparts, to evaluate the pharmacodynamic effects of BIIB054 on the integrity of nigrostriatal dopaminergic nerve terminals and to evaluate the immunogenicity of BIIB054.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Presence of freezing of gait.
- •Montreal cognitive assessment (MOCA) score <23 or other significant cognitive impairment or clinical dementia that, in the opinion of the Investigator, would interfere with study evaluation.
- •History of or screening brain magnetic resonance imaging (MRI) scan indicative of clinically significant abnormality, as read by central reader.
- •History of severe allergic or anaphylactic reactions, or history of hypersensitivity to BIIB054 or any of the inactive ingredients in the drug product or to radioligands or iodine used in the study.
- •Participation in any active immunotherapy study targeting alpha-synuclein.
- •Use of allowed medications not previously specified at doses that have not been stable for at least 8 weeks before Day 1, and/or that are not expected to remain stable for the duration of the study.
- •Clinically significant abnormal laboratory test values at Screening, as determined by the Investigator.
- •Blood donation (1 unit or more) within 8 weeks before Day 1 (must also refrain from donating blood for the duration of the study).
- •NOTE : Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Placebo
Year 1: Participants will receive matching placebo to BIIB054 on Day 1 and then every 4 weeks.
Year 2: Participants who received placebo in year 1 will be randomized into one of the active treatment arms in year 2 and will receive BIIB054 intravenous (IV) infusion on Week 52 and then every 4 weeks.
干预措施: Placebo (Drug)
BIIB054 250 mg
Participants will receive BIIB054 250 milligrams (mg) intravenous (IV) infusion on Day 1 and then every 4 weeks.
干预措施: BIIB054 (Drug)
BIIB054 1250 mg
Participants will receive BIIB054 1250 mg IV infusion on Day 1 and then every 4 weeks.
干预措施: BIIB054 (Drug)
BIIB054 3500 mg
Participants will receive BIIB054 3500 mg IV infusion on Day 1 and then every 4 weeks.
干预措施: BIIB054 (Drug)
结局指标
主要结局
Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52
时间窗: Baseline, Week 52
MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. Part III assessed the motor signs of PD and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 72
时间窗: Baseline, Week 72
MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. Part III assessed the motor signs of PD and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.
次要结局
- Change From Baseline in Striatal Binding Ratio (SBR) in the Putamen as Measured by Single-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter (DaT) at Week 52(Baseline, Week 52)
- Serum Concentration of BIIB054(Pre-dose and 1 hour post-dose of Baseline, Weeks 4, 8, 12, 16, 24, 32, 36, 44, 52, 60, 68, 84, 96, 120 and 144)
- Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 3 years)
- Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at Week 96(Baseline, Week 96)
- Change From Baseline in MDS-UPDRS Subpart II Score at Weeks 72 and 96(Baseline, Weeks 72 and 96)
- Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at Week 52(Baseline, Week 52)
- Percentage of Participants With Anti-BIIB054 Antibodies in the Serum(Up to Week 144)
- Change From Baseline in MDS-UPDRS Subpart I Score at Week 52(Baseline, Week 52)
- Change From Baseline in MDS-UPDRS Subpart I Score at Weeks 72 and 96(Baseline, Weeks 72 and 96)
- Change From Baseline in MDS-UPDRS Subpart II Score at Week 52(Baseline, Week 52)
- Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at Week 52(Baseline, Week 52)
- Change From Baseline in MDS-UPDRS Subpart III Score at Week 52(Baseline, Week 52)
- Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 96(Baseline, Weeks 72 and 96)