A Phase 1a, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of PMN310 Infusions in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Incidence of Treatment Emergent Adverse Events
研究概览
简要总结
This first in human Phase 1a clinical trial will evaluate the safety, tolerability, and pharmacokinetics of a single IV infusion of PMN310 in healthy volunteers.
详细描述
This randomized, double-blind, placebo-controlled study will evaluate the safety, tolerability and pharmacokinetics of single ascending doses of intravenous PMN310 in healthy adult volunteers.
Subjects will be randomly assigned to receive either a single infusion of PMN310 or placebo. After randomization on Day 1, study drug will be administered followed by the collection of safety, tolerability, and PK data.
All dose cohorts will have lumbar punctures (LPs) for PK analysis performed on Day 3 and Day 29. Primary PK and CSF data will be obtained from Day 1 to Day 29. Safety and tolerability will be collected at all visits. The study is an 85-day study with one optional follow up assessment at Day 120.
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
- Double (Participant, Investigator)
盲法说明
Double blind
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Female subjects of childbearing potential must not be breastfeeding and must have no plans to become pregnant during the course of the study through 120 days after infusion of study drug.
- •Female subjects of non-childbearing potential must have evidence from their medical history indicating that they are not of childbearing potential.
- •Any non-vasectomized male subjects must agree to use barrier contraceptives (male or female partner condom, diaphragm, cervical cap, sponges) plus spermicide.
- •Medically healthy with no clinically significant or relevant abnormalities in medical history, physical exam, vital signs, ECG, or laboratory evaluations.
- •Has provided written informed consent.
- •Body mass index is between 18 and 32 kg/m2 (inclusive).
- •Screening MRI normal.
排除标准
- •Clinically significant 12-lead ECG abnormality at Screening.
- •Systolic blood pressure > 150 bpm or diastolic blood pressure > 90 bpm at Screening.
- •Experienced a significant systemic illness within 30 days of the first dose of study drug.
- •Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
- •Currently using any medication except for acetaminophen as needed for miscellaneous aches and pains.
- •History of alcohol abuse and/or illicit drug use within 12 months prior dosing or a smoking history (use of tobacco products).
- •Unwilling to refrain from ingesting alcohol within the limits required by the Study.
- •Positive urine drug screen.
- •History of prior malignancy.
- •Documented history of human immunodeficiency virus (HIV) antibody or tested positive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody at Screening.
- •Donated blood or blood products (e.g., plasma, platelets) within 28 days prior to first dose.
- •Received an investigational agent within the last 30 days or 5 half-lives (if known) prior to Screening, whichever is longer.
- •Contraindication to brain venipuncture, MRI or LP.
- •Indication of potential suicidality risk as identified by the following Columbia-Suicide Severity Rating Scale (C SSRS).
研究组 & 干预措施
Cohort 3 PMN310 700mg or placebo
PMN310 700mg or placebo administered as a 60-minute infusion.
干预措施: PMN310 (Drug)
Cohort 1 PMN310 175mg or placebo
PMN310 175mg or placebo administered as a 60-minute infusion.
干预措施: PMN310 (Drug)
Cohort 1 PMN310 175mg or placebo
PMN310 175mg or placebo administered as a 60-minute infusion.
干预措施: Placebo (Drug)
Cohort 2 PMN310 350mg or placebo
PMN310 350mg or placebo administered as a 60-minute infusion.
干预措施: PMN310 (Drug)
Cohort 2 PMN310 350mg or placebo
PMN310 350mg or placebo administered as a 60-minute infusion.
干预措施: Placebo (Drug)
Cohort 3 PMN310 700mg or placebo
PMN310 700mg or placebo administered as a 60-minute infusion.
干预措施: Placebo (Drug)
Cohort 4 PMN310 1400mg or placebo
PMN310 1400mg or placebo administered as a 60-minute infusion.
干预措施: PMN310 (Drug)
Cohort 4 PMN310 1400mg or placebo
PMN310 1400mg or placebo administered as a 60-minute infusion.
干预措施: Placebo (Drug)
Cohort 5 PMN310 2800mg or placebo
PMN310 2800mg or placebo administered as a 60-minute infusion.
干预措施: PMN310 (Drug)
Cohort 5 PMN310 2800mg or placebo
PMN310 2800mg or placebo administered as a 60-minute infusion.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Treatment Emergent Adverse Events
时间窗: 85 days
Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects.
Incidence of Clinically Significant Abnormal Findings in Laboratory Assessments (Hematology, Serum Clinical Chemistry, and Urinalysis)
时间窗: 85 days
Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects.
Incidence of Clinically Significant Abnormal Findings in Physical Examinations Including Neurological Examinations
时间窗: 85 days
Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects.
Incidence of Clinically Significant Abnormal Findings in Vital Signs (Supine Blood Pressure (BP), Pulse, Respiratory Rate and Oral Body Temperature)
时间窗: 85 days
Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects.
Incidence of Clinically Significant Abnormal Findings in 12 Lead Electrocardiogram (ECG)
时间窗: 85 days
Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects.
次要结局
- Summary of Serum Pharmacokinetic Parameters of PMN310 - AUCinf(0 to 2040 hours post-dose)
- Summary of CSF Concentrations of PMN310(Days 3 and 29)
- Summary of Serum Pharmacokinetic Parameters of PMN310 - AUClast(0 to 2040 hours post-dose)
- Summary of Serum Pharmacokinetic Parameters of PMN310 - CL(0 to 2040 hours post-dose)
- Summary of Serum Pharmacokinetic Parameters of PMN310 - Cmax(0 to 2040 hours post-dose)
- Summary of Serum Pharmacokinetic Parameters of PMN310 - T1/2(0 to 2040 hours post-dose)
- Summary of Serum Pharmacokinetic Parameters of PMN310 - Tmax(0 to 2040 hours post-dose)
- Summary of Serum Pharmacokinetic Parameters of PMN310 - Vd(0 to 2040 hours post-dose)