A Phase 3, Randomized, Double-Blind, Placebo-Controlled (Older Adults, Aged >60 to 79 Years) and Open-Label (Adults, Aged 45 to 60 Years), Multicenter Trial to Investigate the Safety and Immunogenicity of a Dengue Tetravalent Vaccine (TDV) Administered Subcutaneously to Adults and Older Adults With or Without Comorbidities in Endemic Areas for Dengue
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 800
- 试验地点
- 7
- 主要终点
- Number of Participants with Solicited Local (Injection Site) Adverse Events (AEs) Within 7 Days Post Vaccination at Day 1
研究概览
简要总结
Dengue fever is caused by an infection with the dengue virus. Vaccination with Dengue Tetravalent Vaccine (TDV) can help prevent dengue fever. Researchers have seen that dengue fever now also happens more often in elderly persons. The main aim of this study is to learn more about the side effects of TDV in adult (45 - 60 years) and elderly (60 - 79 years) persons and about TDV's ability to create an immune response in adult and elderly persons. Another aim is to learn about the side effects of TDV in adult and elderly persons in endemic countries who have one or more additional medical conditions (called comorbidities) such as diabetes mellitus, hypertension or a chronic kidney condition.
In this study, participants will receive 2 vaccinations with TDV (the second 3 months after the first).
During the study, participants will visit their study clinic 5 times.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Cohort 1 is randomized and double-blinded. Cohort 2 is non-randomized and open label.
入排标准
- 年龄范围
- 45 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant is aged 45 to 79 years at the time of entry into the trial.
- •Participant is male or female.
- •Participant is in good health or has a medical diagnosis of one or more of diabetes mellitus, hypertension, or chronic kidney disease (that is, comorbidities) and are medically stable in the opinion of the investigator at the time of entry into the trial, as determined by medical history and targeted physical examination. Medically stable is defined as no change in diagnoses or chronic medications (dose or class) for medical reasons in the 3 months prior to participating in the trial.
- •Participant has signed and dated a written informed consent form and any required privacy authorization prior to the initiation of any trial procedure, and after the nature of the trial has been explained according to local regulatory requirements.
- •Participant can comply with trial procedures and is available for the duration of follow-up.
排除标准
- •Participant has contraindication(s), warning(s), and/or precaution(s) applicable to vaccination with TDV as specified in the Investigator's Brochure and/or approved product label (as applicable) in the participating country.
- •Participant has a known hypersensitivity or allergy to any of the TDV or placebo components (including excipients).
- •Participant has behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, could interfere with the participant's ability to take part in the trial.
- •Participant has a history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (example, Guillain-Barré syndrome).
- •Participant has an illness, or history of any illness that, in the opinion of the investigator, might interfere with the results of the trial or pose additional risk to the participant due to involvement in this trial.
- •Participant has a known or suspected altered immunocompetence, including:
- •Chronic administration of oral and/or parenteral steroids at doses considered sufficiently immunosuppressive (example, greater than or equal to [>=] 2 milligram per kilogram [mg/kg] body weight prednisone [or equivalent] for >=14 consecutive days, or >=20 milligram per day [mg/day] prednisone [or equivalent] administered for >=14 consecutive days) within 60 days prior to Day 1 (month [M0]) (note: use of corticosteroids by inhaled, intranasal, intra-articular, bursal, tendon injection, or topical routes is allowed).
- •Receipt of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (M0) or planned administration during the trial.
- •Receipt of immunostimulants within 60 days prior to Day 1 (M0).
- •Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (M0).
- •Human Immunodeficiency Virus (HIV) infection or HIV-related disease.
- •Hepatitis B virus infection.
- •Hepatitis C virus infection.
- •Genetic immunodeficiency.
- •Participant has known or suspected abnormalities of splenic or thymic function.
- •Participant has a known bleeding diathesis, or any condition/medication that may be associated with a prolonged bleeding time.
- •Participant has a serious chronic or progressive disease deemed to be preclusive to trial entry, that is, not medically stable according to the judgment of the investigator.
- •Participant has previously received a vaccination against dengue virus (investigational or licensed).
- •Participant had a clinically significant active infection (as assessed by the investigator) or body temperature >38.0 degree Celsius (>100.4 degree Fahrenheit) within 3 days of intended TDV or placebo administration.
- •Participant has used antipyretics and/or analgesic medications within 24 hours prior to vaccination. The reason for their use (prophylaxis vs treatment) must be documented. Trial entry must be delayed to allow for a full 24 hours to have passed since the last use of antipyretics and/or analgesic medications.
- •Participant has a history of substance or alcohol abuse within the past 2 years.
- •Female participants who are pregnant (that is, a positive or indeterminate pregnancy test).
- •Female participants who are breastfeeding.
- •Female participants 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 (M0).
- •Female participants of childbearing potential who are sexually active and who refuse to use an acceptable contraceptive method up to 6 weeks post final vaccination on Day 90 (M3). In addition, they must also be advised not to donate ova during this period.
- •Participant has received any of the following:
- •A licensed vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to TDV or placebo administration on Day 1 (M0). This includes co-administration with routine vaccines.
- •A coronavirus vaccine within 14 days prior to TDV or placebo administration.
- •A vaccine authorized for emergency use within 28 days prior to TDV or placebo administration.
- •Participant is scheduled to receive any other vaccine within 28 days after TDV or placebo administration.
- •Participant is participating in any clinical trial with another investigational product 30 days prior to Day 1 (M0) or intending to participate in another clinical trial at any time during the conduct of this trial.
- •Participant has taken part in any clinical trial of a dengue or other flavivirus (example, West Nile virus) candidate vaccine, except if it is known that the participant received placebo in those trials.
- •Participant or their first-degree relatives are involved in the trial conduct.
- •Participant identified as an employee of the investigator or trial center, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial center.
研究组 & 干预措施
Cohort 1: Tetravalent Dengue Vaccine (TDV) 0.5 mL
Participants with the age group greater than (>) 60 to 79 years will receive TDV, 0.5 mL subcutaneous (SC) injections, on Day 1 and Day 90.
干预措施: TDV (Biological)
Cohort 1: Placebo
Participants with the age group >60 to 79 years will receive placebo (normal saline), 0.5 mL SC injections, on Day 1 and Day 90.
干预措施: Placebo (Other)
Cohort 2: TDV 0.5 mL
Participants with the age group 45 to 60 years will receive TDV, 0.5 mL SC injection, on Day 1 and Day 90.
干预措施: TDV (Biological)
结局指标
主要结局
Number of Participants with Solicited Local (Injection Site) Adverse Events (AEs) Within 7 Days Post Vaccination at Day 1
时间窗: Within 7 days post-vaccination at Day 1
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medical product (IMP); it does not necessarily have to have a causal relationship with IMP administration. Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. All solicited AEs at the injection site will be considered related to the study vaccine administration.
Number of Participants with Solicited Local (Injection Site) Adverse Events (AEs) Within 7 Days Post Vaccination at Day 90
时间窗: Within 7 days post-vaccination at Day 90
Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. All solicited AEs at the injection site will be considered related to the study vaccine administration.
Number of Participants with Solicited Systemic AEs Within 14 Days Post Vaccination at Day 1
时间窗: Within 14 days post-vaccination at Day 1
Solicited systemic AEs include fever (body temperature greater than or equal to \[\>=\] 38 degree Celsius \[C\], asthenia, malaise, headache, and myalgia.
Number of Participants with Solicited Systemic AEs Within 14 Days Post Vaccination at Day 90
时间窗: Within 14 days post-vaccination at Day 90
Solicited systemic AEs include fever (body temperature \>= 38 degree (C), asthenia, malaise, headache, and myalgia.
Percentage of Participants with Solicited Local (Injection Site) AEs by Severity Within 7 Days Post Vaccination at Day 1
时间窗: Within 7 days post-vaccination at Day 1
Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. All solicited AEs at the injection site will be considered related to the study vaccine administration. The AEs will be graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe.
Percentage of Participants with Solicited Local (Injection Site) AEs by Severity Within 7 Days Post Vaccination at Day 90
时间窗: Within 7 days post-vaccination at Day 90
Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. All solicited AEs at the injection site will be considered related to the study vaccine administration. The AEs will be graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe.
Percentage of Participants with Solicited Systemic AEs by Severity Within 14 Days Post Vaccination at Day 1
时间窗: Within 14 days post-vaccination at Day 1
Solicited systemic AEs include fever (body temperature \>= 38 degree (C), asthenia, malaise, headache, and myalgia. The AEs will be graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe.
Percentage of Participants with Solicited Systemic AEs by Severity Within 14 Days Post Vaccination at Day 90
时间窗: Within 14 days post-vaccination at Day 90
Solicited systemic AEs include fever (body temperature \>= 38 degree (C), asthenia, malaise, headache, and myalgia. The AEs will be graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe.
Percentage of Participants with Any Unsolicited AEs Within 28 Days Post Vaccination at Day 1
时间窗: Within 28 days post-vaccination at Day 1
An unsolicited AE is any AE reported by the participant that is not specified as a solicited AE or is specified as a solicited AE but starts outside the period for reporting a solicited AE (that is, 7 days and 14 days in total including the day IMP administration).
Percentage of Participants with Any Unsolicited AEs Within 28 Days Post Vaccination at Day 90
时间窗: Within 28 days post-vaccination at Day 90
An unsolicited AE is any AE reported by the participant that is not specified as a solicited AE or is specified as a solicited AE but starts outside the period for reporting a solicited AE (that is, 7 days and 14 days in total including the day of IMP administration).
Percentage of Participants with a Serious Adverse Event (SAE)
时间窗: From first vaccination on Day 1 through the end of trial (up to Day 270)
An SAE is defined as any untoward medical occurrence that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/ incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, is an important medical event.
Geometric Mean Titers (GMTs) of Neutralizing Antibodies by Microneutralization Test (MNT) for Each of the 4 Dengue Virus Serotypes at Day 120
时间窗: At Day 120
GMTs of neutralizing antibodies will be measured by microneutralization test 50% \[MNT50\] for each of the 4 Dengue Serotypes in all participants. The 4 dengue virus serotypes are dengue virus (DENV)-1, DENV-2, DENV-3 and DENV-4.
次要结局
- Number of Participants with Solicited Local (Injection Site) AEs Within 7 Days Post Vaccination at Day 1 and Day 90 (With Comorbidities)(Within 7 days post-vaccination at Day 1 and Day 90)
- Number of Participants with Solicited Systemic AEs Within 14 Days Post Vaccination at Day 1 and Day 90 (With Comorbidities)(Within 14 days post-vaccination at Day 1 and Day 90)
- Percentage of Participants with Solicited Local (Injection Site) AEs by Severity Within 7 days Post Vaccination at Day 1 and Day 90 (With Comorbidities)(Within 7 days post-vaccination at Day 1 and Day 90)
- Percentage of Participants with Solicited Systemic AEs by Severity (With Comorbidities)(Within 14 days post-vaccination at Day 1 and Day 90)
- Percentage of Participants with Any Unsolicited AEs Within 28 Days Post Vaccination (With Comorbidities)(Within 28 days post-vaccination at Day 1 and Day 90)
- Percentage of Participants with a SAE (With Comorbidities)(From first vaccination on Day 1 through the end of trial (up to Day 270))
- Geometric Mean Titers by MNT for Each of the 4 Dengue Virus Serotypes(Day 1, Day 30, Day 90 and Day 270)
- Geometric Mean Titers by MNT for Each of the 4 Dengue Virus Serotypes (With Comorbidities)(Day 1, Day 30, Day 90, Day 120 and Day 270)
- Seropositivity Rate for Each of the 4 Dengue Virus Serotypes(Day 1, Day 30, Day 90, Day 120 and Day 270)
- Seropositivity Rate for Each of the 4 Dengue Virus Serotypes (With Comorbidities)(Day 1, Day 30, Day 90, Day 120 and Day 270)
- Seropositivity Rate for Multiple (2, 3, or 4) Dengue Virus Serotypes(Day 1, Day 30, Day 90, Day 120 and Day 270)
- Seropositivity Rate for Multiple (2, 3, or 4) Dengue Virus Serotypes (With Comorbidities)(Day 1, Day 30, Day 90, Day 120 and Day 270)