A Phase II, Double-Blind, Randomized, Controlled Trial to Assess the Safety and Immunogenicity of a Tetravalent Dengue Vaccine With Two Different Serotype 2 Potencies in an Adult Population in Singapore
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 351
- 试验地点
- 6
- 主要终点
- Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 180
研究概览
简要总结
The purpose of this study is to assess the post-vaccination neutralizing antibody response against each dengue serotype by vaccine group.
详细描述
The vaccine being tested in this study was Takeda's Tetravalent Dengue Vaccine Candidate (TDV). TDV is being tested to protect people against dengue fever. This study looked at safety and the titers of antibodies to dengue fever induced in people who were administered a high-dose of TDV (HD-TDV) compared to TDV.
The study enrolled 351 patients. Before being assigned to a treatment group participants were screened for previous exposure to the dengue virus using a Dengue immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA). Participants were randomly assigned in 1:1 ratio (by chance) to one of the two treatment groups-which remained undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):
- HD-TDV 0.5 mL subcutaneous injection
- TDV 0.5 mL subcutaneous injection
All participants received a single injection on Day 1. Participants were asked to record any symptoms that may or may not be related to the vaccine or the injection site in a diary card for 28 days after vaccination.
This multi-center trial was conducted in Singapore. The overall time of participation in this study was 12 months. Participants made multiple visits to the clinic, including a final visit 1 year after receiving their dose of TDV.
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
- 21 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant signs and dates a written informed consent form where applicable, and any required privacy authorization prior to the initiation of any trial procedures, after the nature of the trial has been explained according to local regulatory requirements.
- •Is aged 21 to 45 years of age, inclusive.
- •Is in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and clinical judgment of the Investigator.
- •Can comply with trial procedures and are available for the duration of follow-up.
- •Has self-declared as never having been vaccinated against Yellow Fever or Japanese Encephalitis Virus.
排除标准
- •Has febrile illness (temperature ≥38°C or ≥100.4°F) or moderate or severe acute illness or infection at the time of enrollment.
- •Has history or any illness that, in the opinion of the Investigator, might interfere with the results of the trial or pose an additional risk to the participant due to participation in the trial, including but not limited to:
- •Known hypersensitivity or allergy to any of the vaccine components.
- •Female participants who are pregnant or breastfeeding.
- •Individuals with any serious chronic or progressive disease according to judgment of the Investigator (e.g. neoplasm, insulin-dependent diabetes, cardiac, renal or hepatic disease, neurologic or seizure disorder or Guillain-Barré syndrome).
- •Known or suspected impairment/alteration of immune function, including:
- •i. Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (Month 0) (use of inhaled, intranasal, or topical corticosteroids is allowed).
- •ii. Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥ 2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (Month 0).
- •iii. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (Month 0) or planned administration during the trial.
- •iv. Receipt of immunostimulants within 60 days prior to Day 1(Month 0).
- •v. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (Month 0).
- •vi. Human immunodeficiency virus (HIV) infection and HIV-related diseases.
- •vii. Hepatitis C virus (HCV) infection.
- •viii. Genetic immunodeficiency.
- •Has received any other vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to Day 1 (Month 0) or planning to receive any vaccine within 28 days after Day 1 (Month 0).
- •Has participated in any clinical trial with another investigational product 30 days prior to Day 1 (Month 0) or intent to participate in another clinical trial at any time during the conduct of this trial.
- •Has previously participated in any clinical trial of a dengue candidate vaccine, or previous receipt of a dengue vaccine.
- •Is first-degree relative of individuals involved in trial conduct.
- •For females of childbearing potential who are sexually active, and who have not used any of the acceptable contraceptive methods for at least 2 months prior to Day 1 (Month 0).
- •Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: bilateral tubal ligation (at least 1 year previously), bilateral oophorectomy (at least 1 year previously) or hysterectomy.
- •Acceptable birth control methods are defined as one or more of the following:
- •i. Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring).
- •ii. Barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse.
- •iii. Intrauterine device (IUD).
- •iv. Monogamous relationship with vasectomized partner (partner must have been vasectomized for at least six months prior to Day 1 [Month 0]).
- •Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method from signing the informed consent up to 6 weeks post-vaccination.
结局指标
主要结局
Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 180
时间窗: Day 180
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 180
时间窗: Day 180
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 15
时间窗: Day 15
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by microneutralization test \[MNT\].
Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 90
时间窗: Day 90
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.
Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 365
时间窗: Day 365
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 30
时间窗: Day 30
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 90
时间窗: Day 90
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 30
时间窗: Day 30
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 15
时间窗: Day 15
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 365
时间窗: Day 365
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
次要结局
- Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) Following Vaccination by Severity(Within 7 days after Vaccination)
- Number of Participants With Serious Adverse Events (SAEs)(From first vaccination through end of study (Day 365))
- Duration of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination(Days 5, 7, 9, 11, 15, 17, 21 and 30)
- Level of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination(Days 5, 7, 9, 11, 15, 17, 21 and 30)
- Number of Participants With at Least One Unsolicited Adverse Events (AEs) Following Vaccination(Within 28 days after Vaccination)
- Percentage of Participants Positive for Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination(Days 5, 7, 9, 11, 15, 17, 21 and 30)
- Number of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) Following Vaccination by Severity(Within 14 days after Vaccination)
- Geometric Mean Neutralizing Antibody Titers (GMT) for Each of the Four Dengue Serotypes Assessed by Dengue Baseline Seropositivity (MNT) Status(Days 15, 30, 90, 180 and 365)
- Seropositivity Rate for Each of the Four Dengue Serotypes Assessed by Dengue Baseline Seropositivity (MNT) Status(Days 15, 30, 90, 180, and 365)