A Phase I/II Dose-finding Randomized, Single-center, Double-blind, Placebo-controlled Safety and Immunogenicity Trial of the Vesicular Stomatitis Virus-vectored Zaire Ebola Candidate Vaccine BPSC1001 (VSVΔG-ZEBOV) in Healthy Adults.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 115
- 试验地点
- 2
- 主要终点
- Titers of ZEBOV-specific IgG Antibodies
研究概览
简要总结
The hemorrhagic fever resulting from Ebola infection is frequently fatal; the current Ebola outbreak, still in its ascendant phase, has a mortality rate over 50%. There is no proven therapy or prevention available at this time.
The vaccine candidate VSV-ZEBOV (BPSC1001) has shown promising safety and efficacy in preventing Ebola Zaire infections in non-human primates (NHP). Before it can be assessed in large Phase IIb/3 trials in affected areas, safety data from phase 1 first-in-human trials are needed. To accelerate this process, the World Health Organization (WHO) has constituted a consortium of Clinical Research Centers in Switzerland, Germany, and Africa that will use similar protocols to collectively include roughly 250 volunteers, the sample size required to identify a 2-fold difference in anti-ZEBOV IgG antibody titers following immunization with 2 different doses of BPSC1001.
The joint primary objectives of this single-center, double-blind, randomized placebo-controlled phase 1 dose-finding study are to assess the safety and tolerability of the VSV-ZEBOV vaccine when administered to healthy volunteers at a lower or higher vaccine dose and to define whether seroresponses differ significantly following immunization with the lower or higher vaccine dose.
详细描述
This single-center, double-blind, randomized placebo-controlled phase 1 dose-finding study will have two randomization schemes. Volunteers who could later be exposed to Ebolavirus while working in epidemic areas ("deployable subjects") will be randomized to receive one of two vaccine doses. Non-deployable volunteers, with no identified risk of Ebola exposure in the near term, will be allocated to one of three groups and receive the lower or higher vaccine dose, or a placebo. A single immunization will be performed. All subjects will be observed in the clinical trials unit (CTU) for 1.5 hours after vaccine/placebo injection. Subjects will complete post-injection diaries for 7 days after injection, as well as post-injection follow-up visits (see below). On-site visits at the CTU will occur on days -90 to -1, 0, 1, 3, 7, 14, 28, 84, 168. Some subjects with a positive serologic response at 24 weeks may be requested to return for immune durability testing at 12 months.
One or more interim analyses will be undertaken to guide decisions on 1) the potential use of the vaccine in Ph2/3 trials in affected countries and 2) potential modification of the trial(s) through an amendment to evaluate a higher dose, if immunogenicity is poor, or a lower dose if the dosage levels selected are not safe and reasonably well tolerated.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Has provided written informed consent before screening
- •Adult male or non-pregnant, non-lactating female, ages 18 to 65 (inclusive) at the time of screening
- •Free of clinically significant health problems, as determined by pertinent medical history and clinical examination at study screening
- •Females of childbearing potential who are willing to use an effective method of contraception, from at least 7 days prior to vaccination through the end of the study period, and a double method from day 0 through day 28
- •Males who are willing to use effective contraception from day 0 through day 28:
- •Be willing to minimize blood and body fluid exposure of others for 7 days after vaccination
- •Use of effective barrier prophylaxis, such as latex condoms, during penetrative sexual intercourse (avoiding the sharing of needles, razors, or toothbrushes, avoiding open-mouth kissing, be willing to refrain from blood donation during the course of the study)
排除标准
- •Prior receipt of an Ebolavirus or Marburgvirus vaccine, a VSV-vectored vaccine, or any other investigational vaccine likely to impact on interpretation of the trial data
- •Serologic evidence of prior Ebola exposure
- •Has a household contact (HHC) who is immunodeficient, HIV-positive, pregnant, has an unstable medical condition in the opinion of the investigator (e.g., New York Heart Association Class ≥ II heart failure, severe debilitating asthma and/or chronic obstructive pulmonary disease)
- •Works with livestock
- •History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions
- •Known allergy to the components of the BPSC1001 vaccine product
- •Receipt of investigational product up to 30 days prior to enrollment or ongoing participation in another interventional clinical trial
- •Receipt of licensed vaccines within 14 days of planned study immunization (30 days for live vaccines) or ongoing participation in another clinical interventional trial
- •Acute or chronic, clinically significant psychiatric, hematologic, pulmonary, cardiovascular, or hepatic or renal functional abnormality as determined by the Investigator based on medical history, physical exam, and/or laboratory screening test
- •Any baseline laboratory screening tests which is outside of acceptable range as defined in the protocol: ALT, AST, creatinine, hemoglobin, platelet count, total white blood cell count, urine protein, urine occult blood, urine glucose
- •Serologic evidence of hepatitis C infection, evidence of active hepatitis B infection
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, asplenia, cytotoxic therapy in the previous 5 years, and/or diabetes
- •Any chronic or active neurologic disorder, including seizures, and epilepsy, excluding febrile seizures as a child
- •Has a known history of Guillain-Barré Syndrome
- •Has an active malignancy or recent (< 10 years) history of metastatic or hematologic malignancy
- •Suspected or known alcohol and/or illicit drug abuse within the past 5 years
- •Pregnant or lactating female, or female who intends to become pregnant during the study period
- •Administration of immunoglobulins and/or any blood products within the 120 days preceding study entry or planned administration during the study period
- •History of blood donation within 30 days of enrollment or plans to donate within the study period
- •Administration of chronic (> 14 days) immunosuppressants or other immune-modifying drugs within 6 months of study entry
- •Any other significant finding that, in the opinion of the investigator, would increase the risk of the individual's having an adverse outcome by participating in this study
结局指标
主要结局
Titers of ZEBOV-specific IgG Antibodies
时间窗: Day 0 - 28
Primary immunogenicity outcome (required for dose selection)
次要结局
- Number of Participants With a Serious Adverse Event (SAE)(Days 0 - 365)
- Number of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms(Days 0 - 14)
- Number of Participants With Unsolicited Adverse Events(Days 0 - 28)
- Magnitude (Copies/ml) of VSVΔG-ZEBOV Viremia(Days 1, 3 and 7)
- Duration of VSVΔG-ZEBOV Viremia(Days 1, 3 and 7)
- Persistence of Titers of ZEBOV-specific IgG Antibodies(Day 168)
- Titers of Neutralizing ZEBOV-specific IgG Antibodies(Days 0, 28 and 168)
- Number of Participants in Whom Shedding of VSVΔG-ZEBOV Was Detected in Urine and/or Saliva.(Days 1, 3 and 7)
研究者
Siegrist Claire-Anne
Director of Center for Vaccinology
University Hospital, Geneva