A Phase 1 Single- and Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB094 Administered Intrathecally to Adults With Parkinson's Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 17
- 主要终点
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The primary objective of this study is to evaluate the safety and tolerability of single and multiple doses of BIIB094 administered via intrathecal (IT) injection to participants with Parkinson's Disease (PD). The secondary objective of this study is to evaluate the pharmacokinetic (PK) profile of BIIB094.The study is open for PD patients with verified presence or absence of variations in the leucine-rich repeated kinase 2 (LRRK2) gene, but also for patients without any verified PD-related genetic variant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 35 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
- •Diagnosed with PD within 7 years at the time of initial enrollment (i.e., at time of SAD enrollment for rollover participants), without major motor fluctuations or dyskinesia that may interfere with study treatment and assessments in the opinion of the investigator after consultation with the Sponsor.
- •Modified Hoehn and Yahr Stage ≤
排除标准
- •Montreal Cognitive Assessment (MoCA) score less than (<) 23, dementia, or other significant cognitive impairment that, in the opinion of the Investigator, would interfere with study evaluation.
- •History of any brain surgery for PD or a history of focused ultrasound treatment at any time; or history of neuromodulation procedures.
- •Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year before Screening.
- •History of unstable angina, myocardial infarction, chronic heart failure, or clinically significant conduction abnormalities within 1 year before Screening.
- •Poorly controlled diabetes mellitus, as defined by having dosage adjustment of diabetic medication within 3 months before dosing (Day 1) or glycosylated hemoglobin value greater than or equal to (≥) 8 percent (%) at Screening.
- •History or positive test result at Screening for human immunodeficiency virus.
- •History or positive test result at Screening for hepatitis C virus antibody.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part A (SAD): BIIB094 Dose 1
Participants will receive a single IT injection of BIIB094 during Part A [Single Ascending Dose (SAD)].
干预措施: BIIB094 (Drug)
Part A (SAD): BIIB094 Dose 2
Participants will receive a single IT injection of BIIB094 during Part A (SAD).
干预措施: BIIB094 (Drug)
Part A (SAD): BIIB094 Dose 3
Participants will receive a single IT injection of BIIB094 during Part A (SAD).
干预措施: BIIB094 (Drug)
Part A (SAD): BIIB094 Dose 4
Participants will receive a single IT injection of BIIB094 during Part A (SAD).
干预措施: BIIB094 (Drug)
Part A (SAD): BIIB094 Dose 5
Participants will receive a single IT injection of BIIB094 during Part A (SAD).
干预措施: BIIB094 (Drug)
Part A (SAD): BIIB094 Dose 6
Participants will receive a single IT injection of BIIB094 during Part A (SAD).
干预措施: BIIB094 (Drug)
Part B (MAD): BIIB094 Dose 1
Participants will receive a single IT injection of BIIB094 on multiple days during Part B [Multiple Ascending Dose (MAD)].
干预措施: BIIB094 (Drug)
Part B (MAD): BIIB094 (Non LRRK2) Dose 2
Participants [Non leucine-rich repeat kinase 2 (Non LRRK2)] will receive a single IT injection of BIIB094 on multiple days during Part B (MAD).
干预措施: BIIB094 (Drug)
Part B (MAD): BIIB094 (LRRK2) Dose 2
Participants (LRRK2) will receive a single IT injection of BIIB094 on multiple days during Part B (MAD).
干预措施: BIIB094 (Drug)
Part B (MAD): BIIB094 (Non LRRK2) Dose 3
Participants (Non LRRK2) will receive a single IT injection of BIIB094 on multiple days during Part B (MAD).
干预措施: BIIB094 (Drug)
Part B (MAD): BIIB094 (LRRK2) Dose 3
Participants (LRRK2) will receive a single IT injection of BIIB094 on multiple days during Part B (MAD).
干预措施: BIIB094 (Drug)
Part A (SAD): Matching Placebo
Participants will receive matching placebo during Part A [Single Ascending Dose (SAD)].
干预措施: Placebo (Drug)
Part B (MAD): Matching Placebo
Participants will receive matching placebo on multiple days during Part B (MAD).
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Part A: Screening (Day -42) up to Day 85, Part B: Screening (Day -77) up to Day 253
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 SAE is any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event.
次要结局
- Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of BIIB094(Part A: pre-dose through Day 57, Part B: pre-dose through Day 169)
- Terminal Elimination Half-Life (t1/2) of BIIB094(Part A: pre-dose through Day 57, Part B: pre-dose through Day 169)
- Serum Concentrations of BIIB094(Part A: pre-dose through Day 57, Part B: pre-dose through Day 169)
- Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of BIIB094(Part A: pre-dose through Day 57, Part B: pre-dose through Day 169)
- Maximum Concentration (Cmax) of BIIB094(Part A: pre-dose through Day 57, Part B: pre-dose through Day 169)
- Time to Reach Maximum Concentration (Tmax) of BIIB094(Part A: pre-dose through Day 57, Part B: pre-dose through Day 169)