Phase One, Open Label Assessment of a Dengue-3-Virus-Live Virus Human Challenge - (DENV-3-LVHC) Virus Strain
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Number of Serious Adverse Events
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. This study will examine the safety and effectiveness of the Dengue 3 Live Virus Human Challenge (DENV-3-LVHC) product and assess the ability of this virus strain to elicit an uncomplicated dengue-like illness.
详细描述
Healthy subjects between 18 and 45 years old will be inoculated with Dengue 3 Live Virus Human Challenge (DENV-3-LVHC) in a dose ranging study. Subjects will be closely monitored for the first 28 days with continued follow up through 6 months. Clinical and laboratory parameters, viremia and antibody levels will be assessed. The goal is to determine the dose that produces uncomplicated dengue-like illness.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Age 18-45 at the time of consent
- •Ability and willingness to sign informed consent
- •Passing score on comprehension test of at least 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, adenomyosis, and uterine scarring (e.g., after D&C)
- •Blood tests confirming infection with human immunodeficiency virus- 1 (HIV-1), hepatitis C, hepatitis B (assessed by HbsAg) virus, or positive antibodies to the flaviviruses (FV) dengue, West Nile, Yellow Fever, Japanese encephalitis, or Zika.
- •Active Diabetes or active peptic ulcer disease (PUD)
- •Chronic obstructive pulmonary disease (COPD) or coronary artery disease (CAD)
- •Known or suspected congenital or acquired immunodeficiency; or receipt of immunomodulation therapy such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
- •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
- •Diagnosis with Bipolar Disorder or 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 prior to inoculation for the tests specified in Table 18 and Table 19 of the protocol, that are considered by the investigator to be clinically significant except those listed in exclusion criteria 16
- •Subjects with the following grade 2 or greater lab abnormalities: Creatinine; Liver Function Tests - ALT, AST; Hemoglobin (females and males); White Blood Cell (WBC) decrease; Platelets decreased; Prothrombin Time (PT); Partial Thromboplastin Time (PTT); Fibrinogen decrease
- •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 180 days)
- •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
- •Recent blood donation within prior 56 days of inoculation
- •Receipt of blood products or antibodies within 56 days of inoculation or during the study period
- •Participation (active or follow-up phase) 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
- •Recent or scheduled receipt of any vaccine 4 weeks prior to or after virus inoculation
- •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 migraines, in the absence of medication over use
- •Chronic medical condition that, in the opinion of the investigator, impacts subject safety.
结局指标
主要结局
Number of Serious Adverse Events
时间窗: 6 months post virus inoculation
Total number
Number of Abnormal Laboratory Measurements
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Total number of all abnormal labs
Intensity of Unsolicited Injection Site Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Graded according to FDA toxicity scale
Intensity of Unsolicited Systemic Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Graded according to FDA toxicity scale
Duration of Abnormal Laboratory Measurements
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of days of abnormal lab
Duration of Solicited Systemic Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of days per symptom
Occurence of Unsolicited Systemic Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of unsolicited systemic symptoms
Intensity of Abnormal Laboratory Measurements
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Graded according clinical laboratory normals and FDA toxicity scale
Intensity of Solicited Injection Site Symptoms
时间窗: 7 days post virus inoculation
Graded according to FDA toxicity scale
Duration of Unsolicited Injection Site Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of days per symptom
Occurrence of Solicited Injection Site Symptoms
时间窗: 7 days post virus inoculation
Number of solicited symptoms
Duration of Solicited Injection Site Symptoms
时间窗: 7 days post virus inoculation
Number of days per symptom
Occurrence of Unsolicited Injection Site Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of unsolicited site symptoms
Occurrence of Solicited Systemic Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of solicited systemic symptoms
Intensity of Solicited Systemic Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Graded according to FDA toxicity scale
Duration of Unsolicited Systemic Symptoms
时间窗: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of days per symptom
次要结局
- Grade of Rash(Up to 28 days post virus inoculation)
- Grade of Myalgia(Up to 28 days post virus inoculation)
- Occurrence of Rash(Up to 28 days post virus inoculation)
- Incubation period before onset of fever(Up to 28 days post virus inoculation)
- Occurence of fever(Up to 28 days post virus inoculation)
- Occurrence of Headache(Up to 28 days post virus inoculation)
- Grade of Abnormal Liver Function Test [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 Thrombocytopenia(Up to 28 days post virus inoculation)
- Occurrence of Myalgia(Up to 28 days post virus inoculation)
- Grade of Headache(Up to 28 days post virus inoculation)
- Viremia by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)(Up to 28 days post virus inoculation)
- Occurrence of Thrombocytopenia(Up to 28 days post virus inoculation)
- Occurrence of Leukopenia(Up to 28 days post virus inoculation)
- Occurrence of Abnormal Liver Function Test [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)](Up to 28 days post virus inoculation)