A Phase 1, First-In-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PVT401 Following Randomized, Double-blind, Placebo-controlled Single and Multiple Ascending Doses in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: adverse and serious adverse events
研究概览
简要总结
The goal of this clinical trial is to learn what happens to PVT401 when it enters the human body and how it affects the immune system. It will also provide information about the safety of PVT401 after a single dose and after multiple doses. The main questions it aims to answer are:
Will participants experience any side effects when taking PVT401? How long does it take PVT401 to leave the body after it is administered?
Healthy volunteers will participate in either the single ascending dose (SAD) or multiple ascending dose (MAD) phase.
In the SAD phase, participants will:
stay in the clinic for two nights, get one dose of PVT401 or a placebo intravenously (through a vein) on Day 1, have blood drawn periodically throughout their stay and be monitored for side effects, and return to the clinic for 3 follow up visits over the four weeks after dosing.
In the MAD phase, participants will:
stay in the clinic for one night prior to each dose of PVT401 or placebo, and get dosed twice a week for 5 weeks. They will have blood drawn periodically throughout the treatment period and be monitored for side effects, and return to the clinic for 4 follow up visits over the six months after dosing.
详细描述
SAD Phase: four cohorts are planned (n=6 per cohort; 2:1 randomization of PVT401 to placebo). This phase consists of five study visits: Screening, Treatment, and Follow-up (Day 8, Day 15, and Day 29). The Screening and Follow-up visits are outpatient; the Treatment visit includes a two-night inpatient stay from Day -1 to Day 2.
Participants will be admitted to the clinic on Day -1, the day prior to dosing. PK sampling will take place on Day 1, and the safety and tolerability of the study drug will be monitored for each participant in the clinic until Day 2 (24 hours post-dose) checkout.
The decision to advance to the subsequent SAD dose cohort will be made by a Safety Review Committee (SRC) following review of all available safety and tolerability data of participants through Day 8.
After completion of a minimum of four cohorts and with the approval of the SRC, the study will transition to the MAD phase.
MAD Phase: two cohorts are planned (n=6 per cohort; 2:1 randomization of PVT401 to placebo). This phase consists of 15 study visits: Screening: Visit 1, Treatment (Visits 2 - 11, dosing b.i.w. for 5 weeks), and Follow-up (Visits 12 - 15, up to 6 months post-dose).
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)
盲法说明
Sponsor
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
- •Healthy male or female, aged between 18 and 65 years, inclusive at Screening.
- •Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive.
- •Carry the HLA DRB4*0101 or DRB4*0103 allele.
- •Participant is medically healthy (in the opinion of the Investigator), as determined by pre-study medical history and without clinically significant (CS) abnormalities.
- •Female participants must be of non-child-bearing potential, or, if of child-bearing potential, must have negative pregnancy test, agree not to become pregnant or donate ova, and must agree to use adequate contraception.
- •Male participants must agree not to donate sperm and use adequate contraception.
排除标准
- •Any active infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
- •History of hypersensitivity reaction, anaphylaxis or other CS reactions or known allergy to the study drug or its ingredients including but not limited to dextran.
- •History of any CS disorder which, in the opinion of the Investigator would make implementation of the protocol or interpretation of study results difficult, or that would put the participant at risk by participating in the study.
- •History of surgery or hospitalisation within 4 weeks prior to Screening, or surgery planned during the study.
- •Participant has donated blood or blood products or experienced significant blood loss within 2 months prior to the first dose of study drug.
- •Use of any vaccinations within 4 weeks prior to the first dose of study drug.
- •Laboratory results at Screening that indicate inadequate renal function, with estimated creatinine clearance of < 60 mL/min/1.73m
- •Use of any prescription medication within 14 days prior to the first dose of study drug and/or over-the-counter medication/vitamins/supplements/herbal/ plant-derived medications within 7 days prior to the first dose of study drug.
- •Concurrent enrolment in another clinical study, or participation in another clinical study within 30 days or 5 half-lives, whichever is longer, prior to Screening.
- •Regular consumption of > 10 standard alcoholic drinks/week. Participant is unwilling to abstain from alcohol while confined to the study clinic.
- •Positive alcohol breath test at Screening, upon admission to the clinic on Day -
- •Positive urine drugs of abuse test at Screening, upon admission to the clinic on Day -
- •Participant is a heavy smoker, define as more than 2 cigarettes per day or 10 per week.
- •Participant is unwilling to abstain from smoking while confined to the study clinic.
- •Participant is breastfeeding/lactating or pregnant, or planning to breastfeed or become pregnant during the study.
- •Positive Hepatitis B surface antigen (HBsAg), Hepatitis C (HepC) virus antibody, or human immunodeficiency (HIV) antibody tests.
- •Positive for tuberculosis (TB) disease or latent TB infection.
- •Ingestion of poppy seed-containing foods or beverages within 48 hours prior to first dose of study drug.
研究组 & 干预措施
single dose PVT401
PVT401 will be administered as a single intravenous dose to healthy volunteers. There are a minimum of four cohorts planned, with the dose escalating in each subsequent cohort.
干预措施: PVT401 (Drug)
single dose, normal saline
Participants receiving placebo will be administered a single intravenous dose of normal saline at an equivalent volume to a single IV PVT401 dose (mg/kg).
干预措施: Normal Saline (0.9% NaCl) (Drug)
multiple doses, normal saline
Participants receiving placebo will be administered multiple intravenous doses of normal saline at an equivalent volume to the IV PVT401 dose (mg/kg).
干预措施: Normal Saline (0.9% NaCl) (Drug)
multiple doses, PVT401
Following completion of single-dose cohorts, PVT401 will be administered as a multiple intravenous dose treatment regimen to healthy volunteers. There are two cohorts planned, with the dose escalating in each subsequent cohort.
干预措施: PVT401 (Drug)
结局指标
主要结局
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: adverse and serious adverse events
时间窗: From enrollment through 4-weeks post last dose of study drug
Safety endpoints include incidence, severity, and relationship of adverse events (AEs) and serious adverse events (SAEs) (including withdrawals due to AEs)
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: vital signs (temperature)
时间窗: From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
Safety endpoints include change from baseline in vital signs (temperature measured in degrees Celsius)
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: vital signs (heart rate)
时间窗: From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
Safety endpoints include change from baseline in vital signs (heart rate measured in beats per minute)
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: vital signs (blood pressure)
时间窗: From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
Safety endpoints include change from baseline in vital signs (blood pressure measured in mmHg)
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: clinical laboratory parameters (hematology panel)
时间窗: From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
Safety endpoints include change from baseline in clinical laboratory parameters (hematology)
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants.: clinical laboratory parameters (serum chemistry panel)
时间窗: From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
Safety endpoints include change from baseline in clinical laboratory parameters (serum chemistry including liver function tests).
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: clinical laboratory parameters (coagulation panel)
时间窗: From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
Safety endpoints include change from baseline in clinical laboratory parameters (coagulation parameters).
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: clinical laboratory parameters (urinalysis)
时间窗: From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
Safety endpoints include change from baseline in clinical laboratory parameters (urinalysis).
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: clinical laboratory parameters (serum iron panel)
时间窗: From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
Safety endpoints include change from baseline in clinical laboratory parameters (serum iron panel)
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: ECG (PR interval)
时间窗: From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
Safety endpoints include change from baseline in electrocardiogram (ECG) parameters: PR Interval (milliseconds)
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: ECG (QRS duration)
时间窗: From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
Safety endpoints include change from baseline in electrocardiogram (ECG) parameters: QRS Duration (milliseconds)
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: ECG (QT interval)
时间窗: From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
Safety endpoints include change from baseline in electrocardiogram (ECG) parameters: QT Interval (milliseconds)
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: ECG (QTcF)
时间窗: From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
Safety endpoints include change from baseline in electrocardiogram (ECG) parameters: QTcF (milliseconds)
次要结局
- To measure the PK of PVT401 in plasma following single and multiple IV doses in healthy volunteers.(Single Dose Cohorts: multiple timepoints pre-dose to 24 hours post-dose Multiple Dose Cohorts: *First and Last Dose: multiple timepoints from pre-dose to 4 hours post-dose)