A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of KM-819 Treatment to Slow the Progression of Multiple System Atrophy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Percentage change from baseline in putaminal [18F]FP-CIT (18F-FP-CIT Positron Emission Tomography for Correlating Motor and Cognitive Symptoms of Parkinson's Disease) binding
研究概览
简要总结
This trial will the efficacy of KM-819 compared to placebo in subjects with MSA for slowing the progression of MSA.
详细描述
This is a randomized, double-blind, placebo-controlled phase II trial. This trial will be performed in two part: Main study and Ancillary study.
Main Study: Following a 4-week screening period, subjects will be stratified by MSA subtype (MSA-P, -C [MSA-Parkinsonian type, MSA-cerebellar ataxia]) and randomly assigned in a 1:1 ratio either to KM-819 or Placebo groups.
During a treatment period of 36 weeks, subjects will receive pills of either KM-819 or Placebo for oral administration every day from baseline visit. Following this, there will be a safety follow-up period at Week 40.
Ancillary Study: This ancillary study will provide additional information on the continuing efficacy and safety of KM-819. Subjects in either treatment group in the main study who complete the study are eligible to participate in a follow-up, all-subjects-on-treatment (KM-819), open-label ancillary study.
All subjects in the ancillary study will receive KM-819 for additional 36 weeks regardless of their treatment allocation during the main study. During a treatment period of 36 weeks, subjects will receive pills of KM-819 for oral administration every day from visit at Weeks 40.
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
- Double (Participant, 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
- •Must be diagnosed as probable or possible MSA, according to the second consensus criteria for diagnosis of MSA
- •Patients who are able to visit the clinic during the study period to be in the study.
- •≥ 30 years and ≤ 80 years of age at the time of signing the Informed Consent
- •Antiparkinsonian medications should be stable for, at least, one month before enrollment.
- •Body Mass Index (BMI) range of 18.5 to 30 kg/m^2 inclusive at Screening
- •Patient agrees to use acceptable contraceptive methods during the study
- •For women, menopause, sterilization confirmed.
- •For childbearing women, older than 40, and agreed with more than 2 methods of contraception below and agreed with no desire to be pregnant during and after the study, and, agreed with maintaining medically acceptable methods of contraception during for 90 days after the study.
- •Cognitive ability for possible to make self-decision, understand and follow the instruction, to make written signature on consent form.
- •If no ability to walk, patients must be accompanied by caregiver by wheelchair on schedule.
排除标准
- •A diagnosis of drug induced parkinsonism by typical neuroleptic treatment or haloperidol medication.
- •Women who are pregnant or lactating
- •History of suicide attempt. Any recent suicidal ideation (a level of 4 or 5) within the last 3 months prior to Day 1, or has a positive response ('Yes') to either question 4 or 5 of the Columbia Suicide Severity Rating Scale (C-SSRS) at check-in (Day 1), or who is at significant risk to commit suicide, as judged by the Investigator using the C-SSRS at Screening.
- •Febrile illness or symptomatic viral, bacterial (including upper respiratory infection) or fungal (non-cutaneous) infection.
- •Any clinically significant abnormality following the Investigator's review of the physical examination and protocol-defined clinical laboratory tests at Screening or site check-in.
- •Patient has a mean pulse rate < 40
- •Patient has a mean corrected QT interval using Fridericia's formula (QTcF) of > 430 msec (for males) and > 450 msec (for females).
- •History of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsade de pointes, structural heart disease or a family history of Long QT Syndrome.
- •Positive serology test for hepatitis B surface antigen (HBsAg), anti-hepatitis A virus (HAV), immunoglobulin M (IgM), anti-hepatitis C virus (HCV) or anti-human immunodeficiency virus (HIV).
- •Known or suspected hypersensitivity to KM-819, or any components of the formulation(s) used.
- •Patient has a serious medical or surgical condition.
- •Patients unable to understand the consent form, and determined by investigator with too serious problems for participating in the study.
- •Patients unable to visit the clinical site on schedule due to the no ability mobilize.
- •Patients who had brain surgery history.
研究组 & 干预措施
Main Study: KM-819
Subjects will receive 400 mg of KM-819 orally from Week 0 to Week 36.
干预措施: KM-819 (Drug)
Main Study: Placebo
Subjects will receive visually identical placebo pills of KM-819 orally.
干预措施: Placebo (Drug)
Ancillary Study: KM-819
Subjects will receive 400 mg of KM-819 orally from Week 40 to Week 76.
干预措施: KM-819 (Drug)
结局指标
主要结局
Percentage change from baseline in putaminal [18F]FP-CIT (18F-FP-CIT Positron Emission Tomography for Correlating Motor and Cognitive Symptoms of Parkinson's Disease) binding
时间窗: From Baseline to Week 36
To evaluate the efficacy of KM-819 compared to placebo in subjects with MSA for slowing the progression of MSA. The putaminal \[18F\]FP-CIT binding will allow quantification of MSA progression during 36 weeks.
次要结局
- Percentage change from baseline in cerebellar glucose metabolism(From Baseline to Week 36)
- Change from baseline in the Unified Parkinson Disease Rating Scale (UPDRS) III score(From Baseline to Week 36)
- Change from baseline in the Scale for the Assessment and Rating of Ataxia (SARA) score(From Baseline to Week 36)
- Change from baseline in the Montreal Cognitive Assessment (MoCA) score(From Baseline to Week 36)
- Change from baseline in the Beck's Depression Inventory (BDI-II) score(From Baseline to Week 36)
- Number of subjects with adverse events (AEs) and serious AEs (SAEs)(From Screening (Day -4) to Week 40)
- Maximum observed concentration (Cmax)(From Baseline to Week 36)
- Area under the concentration-time curve (AUC)(From Baseline to Week 36)
- Time of maximum observed concentration (Tmax)(From Baseline to Week 36)
- Change from baseline in the Unified Multiple System Atrophy Rating Scale (UMSARS) scores (UMSARS I + II)(From Baseline to Week 36)
- Change from baseline in the UMSARS II scores(From Baseline to Week 36)
- Change from baseline in the UMSARS I scores(From Baseline to Week 36)
- Percentage change from baseline in putaminal glucose metabolism(From Baseline to Week 36)