Phase One, Open Label, Assessment of a Dengue-1-Virus-Live Virus Human Challenge - (DENV-1-LVHC) Virus Strain
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Intensity of Abnormal Laboratory Measurements
研究概览
简要总结
To evaluate the effectiveness of candidate dengue vaccine formulations, it is prudent to develop an appropriate challenge model. To this end, this first-in-human study will examine the safety and effectiveness of the Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) product and assess the ability of this virus strain to elicit an uncomplicated dengue-like illness.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy, male or non-pregnant, non-lactating female
- •Ability and willingness to sign informed consent
- •Passing score on comprehension test would be 75%, with up to 3 attempts
- •Available for the study period
- •Willing to use contraception for the duration of the study.
- •Provide consent for release of medical history records from primary care physician, college or university, urgent care or emergency room visit
排除标准
- •Female: pregnant or lactating
- •Heavy menstrual bleeding within the last 6 months-menstrual periods lasting longer than 6 days, or requiring 5 or more pads or tampons per day.
- •Female subjects using an intrauterine device (IUD) or Mirena®
- •Female subjects with fibroids or uterine polyps, endometriosis, dysmenorrhea, adenomyosis, and uterine scarring (e.g. after D&C)
- •Blood tests confirming infection with human immunodeficiency virus- 1 (HIV-1), hepatitis C, hepatitis B surface antigen, or flavi viruses (FV) to include dengue fever, West Nile, Yellow Fever, and Japanese encephalitis.
- •Diabetes, chronic obstructive pulmonary disease (COPD), peptic ulcer disease (PUD), or coronary artery disease (CAD)
- •Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
- •Immediate family member (e.g. parent, sibling, child) with current, or a history of immunodeficiency or autoimmune disease
- •Current or a history of auto-immune disease
- •History of Guillain Barré syndrome (GBS)
- •Any history of FV infection or FV vaccination; or planned FV vaccination, outside the study protocol, during the study period
- •History of Bipolar Disorder, Schizophrenia, hospitalization in the past year for a mental health disorder, or any other psychiatric condition, which in the opinion of the investigator prevents the subject from participating in the study.
- •Planned travel during the study period (180 days) which would interfere with the ability to complete all study visits
- •Recent (in the past 4 weeks) travel to any dengue endemic area. These potential subjects may be eligible for enrollment a minimum of 4 weeks later
- •Any laboratory abnormalities in the tests specified in Table 19 and Table 20 of the protocol. Note: these laboratory tests can be repeated if the screening physician believes 1) it is thought to be a normal variant of a healthy state or 2) it is a suspected laboratory error
- •Significant screening physical examination abnormalities at the discretion of the investigator
- •Women who intend to become pregnant or men who intend to father a child during the study period (approximately 6 months)
- •Hives, shortness of breath, swelling of the lips or throat, or hospitalization related to a previous vaccination or an allergy to specific medications/animals for which antigens may be in the virus preparations to include: shellfish allergy, fetal bovine serum, L-glutamine, neomycin and streptomycin
- •Planning to donate blood in the 1 year following inoculation with dengue
- •Participation or planned participation in another vaccine, drug, medical device, or medical procedure clinical trial in the 4 weeks prior to this trial, during the trial, or 6 months following inoculation in this clinical trial
- •Beliefs that bar the administration of blood products or transfusions
- •Positive urine screen for cocaine, amphetamines, or opiates
- •Currently taking Methadone or Suboxone
- •Currently taking anti-coagulant medication, aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)
- •Chronic migraine headaches, defined as more than 15 headache days per month over a 3 month period of which more than 8 are migrainous, in the absence of medication over use
- •Chronic medical condition that, in the opinion of the investigator impacts subject safety.
研究组 & 干预措施
Low dose DENV-1-LVHC
Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC) single low dose (0.5 mL of 6.5 x 10^3 plaque forming units/milliliter (PFU/mL) inoculated subcutaneously
干预措施: Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC) (Biological)
Medium dose DENV-1-LVHC
Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC) single medium dose (0.5 mL of 6.5 x 10^4 PFU/mL) inoculated subcutaneously
干预措施: Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC) (Biological)
High dose DENV-1-LVHC
Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC) single high dose (0.5 mL of 6.5 x 10^5 PFU/mL) inoculated subcutaneously
干预措施: Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC) (Biological)
结局指标
主要结局
Intensity of Abnormal Laboratory Measurements
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Duration of Abnormal Laboratory Measurements
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Occurrence of Solicited Injection Site Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Duration of Solicited Injection Site Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of Abnormal Laboratory Measurements
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Occurrence of Solicited Systemic Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Intensity of Unsolicited Systemic Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Intensity of Solicited Injection Site Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Occurrence of unsolicited Injection Site Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Duration of Unsolicited Injection Site Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Intensity of Solicited Systemic Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Duration of Solicited Systemic Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Occurrence of Unsolicited Systemic Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of Serious Adverse Events
时间窗: 6 months post virus inoculation
Intensity of Unsolicited Injection Site Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Duration of Unsolicited Systemic Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
次要结局
- Grade of Headache(Up to 28 days post virus inoculation)
- Occurrence of Thrombocytopenia(Up to 28 days post virus inoculation)
- Viremia by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)(Up to 28 days post virus inoculation)
- Grade of Myalgia(Up to 28 days post virus inoculation)
- Grade of Thrombocytopenia(Up to 28 days post virus inoculation)
- Grade of Liver Function Tests Abnormalities [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)](Up to 28 days post virus inoculation)
- Grade of Leukopenia(Up to 28 days post virus inoculation)
- Grade of Rash(Up to 28 days post virus inoculation)
- Occurrence of Liver Function Tests Abnormalities [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)](Up to 28 days post virus inoculation)
- Occurrence of Leukopenia(Up to 28 days post virus inoculation)
- Incubation period before onset of fever(Up to 28 days post virus inoculation)
- Occurrence of fever without other identifiable cause, such as strep throat or influenza(Up to 28 days post virus inoculation)
- Occurrence of Headache(Up to 28 days post virus inoculation)
- Occurrence of Myalgia(Up to 28 days post virus inoculation)
- Occurrence of Rash(Up to 28 days post virus inoculation)