Observer-blind, Single Center, Controlled Study of 2 Doses of Various Formulations of the WRAIR Live Attenuated Tetravalent Dengue Vaccine Compared to a Placebo Control, Administered on a 0-6-month Schedule, to Healthy Adults
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 1
- 主要终点
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms
研究概览
简要总结
This descriptive study will evaluate the safety and immunogenicity of 5 different formulations of the WRAIR dengue vaccine compared to a placebo.
详细描述
Subjects will be randomized into one of 6 groups. One group will receive a placebo vaccine and the others will receive one of 5 different dengue vaccine formations. Each subject will receive two doses six months apart. Study subjects who elect to participate in a mosquito transmissibility component of the study will undergo mosquito feedings during each of the two assigned follow-up visits after vaccine dose 1. All subjects will have 11 venipunctures during 11 visits (i.e., screening plus 10 study visits) over a period of nine months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
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 female adult 18-45 years at the time of vaccination
- •Free of obvious health problems as established by medical history and physical examination before entering into the study
- •Written informed consent obtained from the subject
- •Able to read the Subject Information Sheet and Consent Form
- •Subjects who the investigator believes can and will comply with the requirements of the protocol
- •Females must be of non-childbearing potential, or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions as defined in the protocol for 30 days prior to vaccination, have a negative pregnancy test within 48 hours prior to vaccination and must agree to continue such precautions for 60 days after completion of the vaccination series
排除标准
- •History of:
- •recurrent migraine headache
- •any neurological or behavioral disorder or seizures
- •drug abuse or alcohol consumption (more than 2 drinks per day)
- •allergic disease/reaction likely to be exacerbated by vaccine
- •urticaria related to mosquito bites requiring medical attention
- •Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal, hematologic or endocrine functional defect
- •Any confirmed or suspected immunosuppressive or immunodeficient condition;
- •Seropositive for HBsAg, anti-HCV or anti-HIV
- •Acute disease at the time of enrollment
- •Chronic hepatomegaly or splenomegaly
- •Use of any investigational or non-registered drug or vaccine within 30 days preceding study or planned use
- •Planned administration of a vaccine not foreseen by the study protocol 30 days ±each vaccine dose
- •Planned move during study
- •Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs or administration of immunoglobulins and/or blood products, within 90 days preceding the first dose or planned administration during the study period
- •Any chronic systemic drug therapy to be continued during the study period
研究组 & 干预措施
DENGUE FORMULATION 17A GROUP
Healthy male or female subjects, between and including 18-45 years of age, who received two doses of Dengue vaccine Formulation 17a, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6.
干预措施: Live attenuated tetravalent dengue vaccine (Biological)
DENGUE FORMULATION 17B GROUP
Healthy male or female subjects, between and including 18-45 years of age, who received two primary doses of Dengue vaccine Formulation 17b, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6, and one booster dose approximately 5-12 months after the second dose.
干预措施: Live attenuated tetravalent dengue vaccine (Biological)
DENGUE FORMULATION 19 GROUP
Healthy male or female subjects, between and including 18-45 years of age, who received two primary doses of Dengue vaccine Formulation 19, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6 and one booster dose approximately 5-12 months after the second dose.
干预措施: Live attenuated tetravalent dengue vaccine (Biological)
PLACEBO GROUP
Healthy male or female subjects, between and including 18-45 years of age, who received two doses of Placebo, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6.
干预措施: Placebo (Biological)
结局指标
主要结局
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
时间窗: During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
时间窗: During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine
Assessed solicited general symptoms were abdominal pain, arthralgia, fatigue, fever \[defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], headache, muscle aches, nausea, pain behind the eyes, photophobia, pruritus, rash and vomiting. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination.
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4
时间窗: At 30 days (Month 7) after Dose 2 of the study vaccine
Titers for DEN-1, DEN-2, DEN-3 and DEN-4 neutralizing antibodies, expressed as Geometric Mean Titers (GMTs), with cut-off values greater than or equal to (≥) 10 estimated dose giving 50% (ED50) signal reduction when compared to a control without serum.
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4 Based on Priming Status
时间窗: At Month 1 post-booster dose of the study vaccine
Titers for DEN 1, DEN 2, DEN 3 and DEN 4 neutralizing antibodies, expressed as Geometric Mean Titers (GMTs), with cut-off values greater than or equal to (≥) 10 estimated dose giving 50% (ED50) signal reduction when compared to a control without serum. Not primed = Not primed by MN50; Primed = Primed by MN50. Primed subject is a subject with neutralizing antibody titer ≥ 10 ED50 at pre-vaccination for at least one DEN type. Not primed subject is a subject with neutralizing antibody titer \<10 ED50 for any DEN type at pre-vaccination.
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4 Based on Priming Status
时间窗: At 5 to 12 months post-Dose 2 of the study vaccine
Titers for DEN-1, DEN-2, DEN-3 and DEN-4 neutralizing antibodies, expressed as Geometric Mean Titers (GMTs), with cut-off values greater than or equal to (≥) 10 estimated dose giving 50% (ED50) signal reduction when compared to a control without serum. Not primed = Not primed by MN50; Primed = Primed by MN50. Primed subject is a subject with neutralizing antibody titer ≥ 10 ED50 at pre-vaccination for at least one DEN type. Not primed subject is a subject with neutralizing antibody titer \<10 ED50 for any DEN type at pre-vaccination.
次要结局
- Number of Subjects With Serious Adverse Events (SAEs)(During the whole primary phase of the study (from Day 0 up to Month 9))
- Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4(At Month 0 and Month 1)
- Number of Subjects With Antibody Titers Above the Assay Cut-off Value (Tetravalent Response) for All Dengue Serotypes(At Months 1 and 7)
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms(During the 21-day (Days 0-20) follow-up after the study vaccine booster dose)
- Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms(During the 21-day (Days 0-20) follow-up after the study vaccine booster dose)
- Number of Subjects With Unsolicited Adverse Events (AEs)(During the 31-day (Days 0-30) follow-up after any study vaccine dose)
- Number of Subjects With Alert Values for Safety Laboratory Determinations(During the 31-day (Days 0-30) follow-up after the study vaccine booster dose)
- Number of Subjects With Abnormal Findings at Dengue Physical Examination(At Month 1 post-booster vaccination)
- Number of Subjects With Suspected and Confirmed Dengue(During the 31-day (Days 0-30) follow-up after the study vaccine booster dose)
- Number of Subjects With Measurable Dengue Viremia(At study Visit 12 (Days 2, 5, 8 or 12) (FU1), study Visit 13 post-booster vaccination (Days 5, 8, 12 or 14) (FU2) and at study Visit 14 (Month 1 post-booster vaccination))
- Number of Subjects With Safety Laboratory Determinations Outside the Normal Ranges(During the 31-day (Days 0-30) follow-up after each vaccine dose (Month 1 and Month 7))
- Number of Subjects With Antibody Titers Above the Assay Cut-off Value for Each DEN Serotype(Before (PRE) and one month after the booster vaccination (Month 1))
- Number of Subjects With Sero-response to Each DEN Type(At Months 1 and 7)
- Number of Subjects With Any, Grade 3 and Related Unsolicited AEs(During the 31-day (Days 0-30) follow-up after the study vaccine booster dose)
- Number of Subjects With SAEs(During the whole booster phase of the study (from pre-vaccination up to Month 6 post-vaccination with the booster dose))
- Number of Subjects With Hematological and Biochemical Determinations Within and Outside the Normal Ranges(At each booster phase visit [pre-booster vaccination (PRE), study Visit 12 post-booster vaccination (Days 2, 5, 8 or 12) (FU1), study Visit 13 post-booster vaccination (Days 5, 8, 12 or 14) (FU2) and at Months 1 and 6 post-booster vaccination])
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms(During the 21-day (Days 0-20) follow-up after Dose 2 of the study vaccine)
- Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms(During the 21-day (Days 0-20) follow-up after Dose 2 of the study vaccine)
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms(During the 21-day (Days 0-20) follow-up after each dose of the study vaccine)
- Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms(During the 21-day (Days 0-20) follow-up after each dose of the study vaccine)
- Number of Subjects With Alert Values for Safety Laboratory Determinations(During the 31-day (Days 0-30) follow-up after each vaccine dose (Month 1 and Month 7))
- Number of Subjects With Abnormal Findings at Dengue Physical Examination(During the 31-day (Days 0-30) follow-up after each vaccine dose and across doses)
- Number of Subjects With Suspected and Confirmed Dengue(During the 31-day (Days 0-30) follow-up after each vaccine dose and across doses)
- Number of Subjects With Measurable Dengue Viremia(During the 31-day (Days 0-30) follow-up after each vaccine dose)
- Number of Subjects With Antibody Titers Above the Assay Cut-off Value for Each DEN Serotype(At Months 0, 1 and 7)