Safety and Pharmacokinetic Evaluation of Zika Virus Immune Globulin in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Number of Subjects With Adverse Events.
研究概览
简要总结
Currently, there are no licensed therapeutics against Zika virus infection. Due to this unmet medical need, Zika Virus Immune Globulin (ZIKV-IG) is being developed as a therapeutic intervention against Zika virus infection. In this first-in-human study, evaluation of ZIKV-IG safety and pharmacokinetics (absorption, metabolism and excretion) will be conducted in healthy adult volunteers.
详细描述
This study will be evaluating safety and pharmacokinetics (PK) of one dose level of ZIKV-IG (50 mL) in healthy adult volunteers. The study is a single-center, double-blind, randomized and placebo-controlled design. The primary objective is to assess safety of intravenously (IV) administered ZIKV-IG, while the secondary objective is to determine the PK profile of ZIKV-IG in healthy adult volunteers.
There will be a total of 30 subjects enrolled into the study; dosing of the first six subjects will be staggered over three separate days, wherein two subjects per day will be randomized 1:1 to either receive 50 mL of placebo IV or 50 mL of ZIKV-IG IV (the total amount of gamma immune globulin [IgG] protein from a single 50mL dose is 4.65g). After the first six subjects are dosed, the remaining 24 subjects will be randomized 2:1 to receive either ZIKV-IG or placebo. A safety monitoring committee will review safety data (collected up to 3 days post-dosing) of the first 12 dosed subjects prior to dosing of the remaining 18 subjects. Overall, there will be 19 subjects randomized to receive ZIKV-IG and 11 subjects randomized to receive placebo on Day 1. On Day 1 (post-dose at 1 hour, 3 hours, 8 hours) and Day 2, safety and PK assessments will be conducted while the subjects are in the Phase 1 clinic. After the discharge on Day 2, the subjects will come back to the clinic for safety and PK assessments on Days 3, 4, 6, 8, 10, 12, 15, 22, 29, 43, 57 and 85. Total study duration for each subject will be up to 4 months (from screening to Day 85).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Informed consent voluntarily signed by subject.
- •Age: 18-55 years of age.
- •Blood type O+ or O-.
- •Body mass index (BMI) of 18-
- •Note: minimum body weight of 50 kg.
- •For female subjects (with male partners) that are not surgically sterilized (e.g., did not undergo hysterectomy, bilateral oophorectomy or tubal ligation), use of an effective method of contraception throughout the trial including:
- •Using hormonal contraception (oral, injectable or implant) continuously for 3 months prior to screening and willing to continue to use hormonal contraception throughout the entire trial.
- •Intrauterine device (IUD) inserted at least 1 month prior to screening.
- •Double barrier type of birth control measure (e.g., condoms, diaphragms, cervical sponge with spermicide).
- •True abstinence.
- •For female subjects who are post-menopausal, documented follicle- stimulating hormone (FSH) ≥40 milli-international units per milliliter (mIU/mL) must be obtained. If the FSH is <40 mIU/mL, the subject must agree to use an acceptable form of contraception (see above).
- •Females of childbearing potential without male sexual partners must be willing to maintain their sexual status as it is throughout the study.
- •For male subjects that have not had a vasectomy, use of a condom with spermicide or true abstinence for the duration of the study. Note: female partners (that are of childbearing potential) of male study subjects (that have not had a vasectomy) should use one of the effective contraception methods (eg, hormonal contraception, IUD or barrier type). Also, male subjects must not donate sperm for the duration of the study.
- •Males without female sexual partners must be willing to maintain their sexual status as it is throughout the study.
- •Healthy as determined by principal investigator or a qualified designate based on medical history, physical exam, vital signs, urinalysis, blood chemistry and hematology test results at screening.
排除标准
- •Use of any investigational product within the past 30 days.
- •Use of any investigational product during the study.
- •Individuals with blood type A, B or AB.
- •Recipient of any blood product within the past 12 months.
- •Plasma donation within 7 days or significant blood loss or blood donation within 56 days of baseline.
- •Blood donation at any time during the study.
- •Females with a hemoglobin level ≤120 g/L.
- •Males with a hemoglobin level <130 g/L.
- •History of hypersensitivity to blood or plasma products.
- •History of allergy to latex or rubber.
- •History of immunoglobulin A (IgA) deficiency.
- •History of hypercoagulable conditions (e.g., deep vein thrombosis or pulmonary embolism).
- •History of myocardial infarction.
- •History of stroke.
- •History of renal impairment/failure.
- •Currently pregnant or lactating or planning to become pregnant during the study.
- •History of flavivirus infection [ZIKV, dengue virus (DENV), West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever virus (YFV)] or vaccination with licensed or investigational flavivirus vaccine.
- •Plans to travel to an area with active flavivirus (e.g., ZIKV and/or DENV) transmission during the study (and up to 10 months after the study drug administration) or has returned from an endemic area with these diseases within 30 days of screening.
- •Positive nucleic acid test (NAT) or serology for ZIKV or positive serology for WNV or DENV.
- •Positive serology test (at screening) for human immunodeficiency virus 1 and 2 (HIV), hepatitis C virus (HCV); positive test for hepatitis B virus (HBV) as determined by HBsAg.
- •History of chronic or acute severe neurologic condition (e.g., diagnosis of Guillain-Barre syndrome, epilepsy, Bell's palsy, meningitis or disease with any focal neurologic deficits).
- •Heavy smokers (≥15cigarettes a day) or electronic cigarette use.
- •History of, or suspected substance abuse problem (including alcohol).
- •Failure of drug (urine) test at screening or baseline.
- •Failure of alcohol (breath) test at screening or baseline.
- •Receipt of a live vaccine within 28 days prior to screening or anticipated receipt of a live vaccine during the study period.
- •Individuals with planned surgical procedures that will occur during the study.
- •An opinion of the investigator that it would be unwise to allow participation of the subject in the study.
研究组 & 干预措施
Zika Virus Immune Globulin (ZIKV-IG)
Single dose of 50 mL Zika Virus Immune Globulin (ZIKV-IG) will be administered intravenously over 33 minutes.
干预措施: Zika Virus Immune Globulin (ZIKV-IG) (Biological)
Placebo (Saline Solution)
Single dose of 50 mL placebo will be administered intravenously over 33 minutes.
干预措施: Placebo (Other)
结局指标
主要结局
Number of Subjects With Adverse Events.
时间窗: Up to Day 85
Number of subjects with of adverse events by severity.
次要结局
- Assessment of Zika Virus Immune Globulin (ZIKV-IG) Clearance (CL)(0-2 hours predose up to Day 85 postdose)
- Assessment of Zika Virus Immune Globulin (ZIKV-IG) Volume of Distribution (Vz)(0-2 hours predose up to Day 85 postdose)
- Assessment of Zika Virus Immune Globulin (ZIKV-IG) Area Under the Curve Up to Last Quantifiable Concentration (AUC0-t)(0-2 hours predose to Day 85 postdose)
- Assessment of Zika Virus Immune Globulin (ZIKV-IG) Half-Life (t1/2)(0-2 hours predose up to Day 85 postdose)
- Assessment of Zika Virus Immune Globulin (ZIKV-IG) Maximum Concentration (Cmax)(0-2 hours predose to Day 85 postdose)
- Assessment of Zika Virus Immune Globulin (ZIKV-IG) Time to Maximum Concentration (Tmax)(0-2 hours predose up to Day 85 postdose)
- Assessment of Zika Virus Immune Globulin (ZIKV-IG) Area Under the Curve Extrapolated to Infinity (AUC0-inf)(0-2 hours predose up to Day 85 postdose)