A Phase 2, Double-blind, Placebo-controlled, Parallel-group Study Followed by an Open-label, Parallel Group Extension Part to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Potential Efficacy of Multiple Doses of ONO-2808 in Patients With Multiple System Atrophy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 92
- 试验地点
- 53
- 主要终点
- Vital signs (blood pressure)
研究概览
简要总结
This is a Phase 2, double-blind, parallel-group, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of multiple doses of ONO-2808 in patients with MSA. This is the first study of ONO-2808 in patients with MSA.
详细描述
This study will consist of a core part, an extension part, and an additional extension part. The purpose of the core part is to evaluate 3 doses of ONO-2808 compared to placebo in MSA patients, including: 1) safety and tolerability, 2) pharmacokinetics, and 3) changes in clinical outcome assessments (COA) and biomarkers considered to be related to the pharmacodynamics and potential efficacy of ONO-2808. The purpose of the extension part and the additional extension part is to evaluate 3 doses of ONO-2808 in MSA patients, including: 1) safety and tolerability and 2) changes in COAs and biomarkers considered to be related to the pharmacodynamics and potential efficacy of ONO-2808.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female or male patients with a diagnosis of clinically-established or clinically-probable MSA according to the novel Movement Disorder Society (MDS) criteria for MSA diagnosis (2022), including patients with MSA of either subtype (MSA-P or MSA-C).
- •Patients at the early stages of the disease, defined as a maximum of 5 years since the onset of one of the following symptoms associated with MSA:
- •Parkinsonism
- •Orthostatic hypotension and/or urinary dysfunction
- •Patients with an anticipated survival of at least 3 years in the opinion of the Investigator.
- •Patients who are able to ambulate without the assistance of another person, defined as the ability to take at least 10 steps and then to turn around and walk at least another 10 steps. Use of assistive devices (e.g., walker or cane) is allowed.
- •Ability to swallow oral medication and be willing to adhere to the study intervention regimen.
排除标准
- •Pregnant or lactating females.
- •Patients with a clinically-significant or unstable medical or surgical condition other than MSA that, in the opinion of the Investigator, might preclude safe completion of the study or might affect the results of the study (e.g., pulmonary, cardiovascular [including bradyarrhythmia], macular edema, and significant renal or hepatic dysfunction).
- •Neurological diseases/disorders other than MSA, such as Parkinson's disease, dementia with Lewy bodies, essential tremor, progressive supranuclear palsy, spinocerebellar ataxia, spastic paraparesis, corticobasal degeneration, or vascular, normal pressure hydrocephalus, pharmacological, or post-encephalitic parkinsonism.
- •Patients with documented liver diseases or cirrhosis.
- •Positive results at Screening for active viral infections that include positive human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) and hepatitis B core antibody, and hepatitis C virus (HCV).
- •Patients with suicide ideation according to the Investigator's clinical judgment per the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening or who have made a suicide attempt in the 6 months before Screening.
研究组 & 干预措施
Placebo Arm
干预措施: Placebo (Drug)
ONO-2808 Arm
干预措施: ONO-2808 (Drug)
结局指标
主要结局
Vital signs (blood pressure)
时间窗: From screening up to follow-up (Week 28)
Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.
Vital signs (pulse rate)
时间窗: From screening up to follow-up (Week 28)
Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.
Vital signs (temperature)
时间窗: From screening up to follow-up (Week 28)
Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.
Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)
时间窗: From screening up to follow-up (Week 28)
Incidence of TEAEs, drug-related TEAEs, TEAEs resulting in study treatment discontinuation, TESAEs, and drug-related TESAEs will be tabulated by system organ class (SOC), preferred term (PT), and severity.
Vital signs (respiratory rate)
时间窗: From screening up to follow-up (Week 28)
Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.
12-lead electrocardiograms (ECGs); parameters such as, but not limited to, heart rate, RR, PR, QRS, QT, and corrected QT intervals (QTcF)
时间窗: From screening up to follow-up (Week 28)
The number of patients with normal, abnormal not clinically significant and abnormal clinically significant of ECG results will be tabulated at each time point.
Clinically-significant abnormal physical examination findings
时间窗: From screening up to follow-up (Week 28)
The number of patients with normal, abnormal not clinically significant and abnormal clinically significant of physical examination results will be tabulated at each time point.
Clinical laboratory abnormalities (hematology, clinical chemistry, and urinalysis)
时间窗: From screening up to follow-up (Week 28)
The number of patients with abnormal laboratory results at any time during the study will be tabulated.
Clinically-abnormal findings in the Columbia Suicide Severity Rating Scale (C-SSRS)
时间窗: From screening up to follow-up (Week 28)
Responses to the suicidality assessment scale (C-SSRS) will be listed.
Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)
时间窗: From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164)
Incidence of TEAEs, drug-related TEAEs, TEAEs resulting in study treatment discontinuation, TESAEs, and drug-related TESAEs will be tabulated by system organ class (SOC), preferred term (PT), and severity.
Vital signs (blood pressure)
时间窗: From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164)
Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.
Vital signs (pulse rate)
时间窗: From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164)
Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.
Vital signs (temperature)
时间窗: From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164)
Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.
Vital signs (respiratory rate)
时间窗: From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164)
Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.
12-lead electrocardiograms (ECGs); parameters such as, but not limited to, heart rate, RR, PR, QRS, QT, and corrected QT intervals (QTcF)
时间窗: From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164)
The number of patients with normal, abnormal not clinically significant and abnormal clinically significant of ECG results will be tabulated at each time point.
Clinically-significant abnormal physical examination findings
时间窗: From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164)
The number of patients with normal, abnormal not clinically significant and abnormal clinically significant of physical examination results will be tabulated at each time point.
Clinical laboratory abnormalities (hematology, clinical chemistry, and urinalysis)
时间窗: From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164)
The number of patients with abnormal laboratory results at any time during the study will be tabulated.
Clinically-abnormal findings in the Columbia Suicide Severity Rating Scale (C-SSRS)
时间窗: From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164)
Responses to the suicidality assessment scale (C-SSRS) will be listed.
次要结局
- Plasma concentration of ONO-2808(Week 2, Week 8, Week 12, and Week 24)
- ONO-2808 concentration in cerebrospinal fluid (CSF)(Week 24)