Safety and Immunogenicity of a Tetravalent Dengue Vaccine in HIV-Positive Adults Aged 18 to 50 Years in Brazil
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 133
- 试验地点
- 8
- 主要终点
- Percentage of Participants With Solicited Injection-Site Reactions
研究概览
简要总结
The aim of the study was to evaluate the safety and immunogenicity of the Dengue vaccine in a population of special interest, such as HIV-positive adults previously exposed to dengue.
Primary Objective:
- To describe the safety of each injection of CYD dengue vaccine in HIV-positive adults previously exposed to dengue.
Secondary Objectives:
- To describe the humoral immune response to each dengue serotype at baseline and after each injection of CYD dengue vaccine in HIV-positive adults previously exposed to dengue.
- To detect the CYD dengue vaccinal viremia post-Inj 1 in HIV-positive adults previously exposed to dengue.
- To describe changes in CD4 count and HIV RNA viral load after each injection of CYD dengue vaccine in HIV-positive adults previously exposed to dengue.
Observational Objective:
- To describe the FV (YF, Dengue, Zika) serological status in the study population at baseline.
详细描述
Eligible subjects were randomized in a 2:1 ratio into 1 of 2 groups to receive 3 injections of either CYD dengue vaccine or placebo at 0, 6, and 12 months. The enrollment of subjects was carried out in two steps, including an early safety data review before the second step. The duration of each subject's participation in the study was approximately 18 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
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 50 years on the day of first study vaccination (study product administration) ("18 to 50" means from the day of the 18th birthday to the day before the 51th birthday)
- •Inform concent form has been signed and dated
- •Able to attend all scheduled visits and to comply with all trial procedures
- •Documented seropositivity for HIV-1 infection based on the Brazilian HIV Guidelines' laboratory criteria (i.e., two positive results obtained from different and independent determination methods) or detectable HIV-1 viral load results in the past
- •Stable HIV condition according to Brazilian HIV Guidelines (i.e., with both CD4 count > 350 cells/mm3 and sustainable and undetectable HIV viral load [< 50 copies/mL]) for at least 1 year before consent
- •Stable antiretroviral (ART) regimen based on local HIV protocol for at least 1 year before consent.
- •Previous exposure to dengue confirmed by rapid diagnostic test (RDT) or dengue IgG ELISA
排除标准
- •Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche or post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination)
- •Participation at the time of study enrollment (or in the 4 weeks preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
- •Receipt of any vaccine in the 4 weeks preceding the first trial vaccination or planned receipt of any vaccine in the 4 weeks following any trial vaccination
- •Previous vaccination against dengue disease with either the trial vaccine or another vaccine
- •Receipt of immune globulins, blood or blood-derived products in the past 3 months
- •Self-reported or suspected congenital or acquired immunodeficiency, except HIV; 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)
- •Previous acquired immunodeficiency syndrome (AIDS), defined as the occurrence of opportunistic infection in the last 2 years before consent
- •Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances
- •Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
- •Current alcohol abuse or drug addiction
- •Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
- •Moderate or severe acute illness/infection (according to investigator judgment) or febrile illness (temperature ≥ 38.0°C) on the day of vaccination. A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided
- •Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study
- •Previous CD4 count < 200 cells/mm3 (nadir) since diagnosis of HIV
- •History of chronic and active hepatitis B infection or HBsAg-positive
- •History of chronic and active hepatitis C infection or HCV Ab-positive
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine > 3 times the upper limit of normal range (ULN)
- •Hemoglobin (Hb) < 10 g/dL
- •White blood cell count (WBC) < 1500 cells/mm3
- •Platelets < 100,000 cells/mm3.
结局指标
主要结局
Percentage of Participants With Solicited Injection-Site Reactions
时间窗: Up to 7 days after each injection
An AE was any untoward medical occurrence in a participant administered study vaccine and which did not necessarily have a causal relationship. A solicited reaction was an expected adverse reaction (AR) observed and reported under the conditions pre-listed in the protocol and CRF and included pain, erythema, and swelling. Injection site reaction was an AR at and around the injection site. Injection site reactions were commonly inflammatory reactions.
Percentage of Participants With Solicited Systemic Reactions
时间窗: Up to 14 days after each injection
A solicited reaction was an "expected" adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF. Solicited systemic reactions included headache, fever, localized or topical manifestations that were not associated with the vaccination or administration site.
Percentage of Participants With Unsolicited AE, Serious and Non-Serious AEs of Special Interest (AESIs)
时间窗: Up to 28 days after each injection
An unsolicited AE was an observed AE that did not fulfill the conditions pre-listed in the protocol and CRF in terms of diagnosis and/or onset window post-vaccination. An AESI was one of scientific and medical concern specific to the study vaccine, for which ongoing monitoring, and rapid communication by the Investigator to the Sponsor was appropriate. The following were considered as serious AESI: serious hypersensitivity/allergic reactions occurring in all participants within 7 days after vaccination; serious viscerotropic disease occurring in all participants within 30 days after vaccination; serious neurotropic disease occurring in all participants within 30 days after vaccination; serious dengue disease requiring hospitalization occurring in all participants at any time during the study. The following were considered as non-serious AESIs, hypersensitivity/allergic reactions occurring in all participants within 7 days after vaccination.
Percentage of Participants With Serious AEs (SAEs) and Hospitalized Virologically-Confirmed Dengue (VCD) Cases
时间窗: From the date of randomization until 6-month safety follow-up (approximately 38 months)
An AE was any untoward medical occurrence in a participant administered study vaccine and which does not necessarily have a causal relationship. SAEs were any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Hospitalized VCD cases were defined as an acute febrile illness with diagnosis of dengue requiring hospitalization. The confirmatory dengue diagnosis was performed through virological detection.
Percentage of Participants With Unsolicited Systemic Adverse Event (AE)
时间窗: Within 30 minutes after each injection
An AE was any untoward medical occurrence in a participant administered study vaccine and which did not necessarily have a causal relationship. An unsolicited AE was an observed AE that did not fulfill the conditions pre-listed in the protocol and case report form (CRF) in terms of diagnosis and/or onset window post-vaccination.
次要结局
- Geometric Mean Titers of Neutralizing Antibody Levels Against Each of the 4 Parental Dengue Virus Strains(Baseline (Day 0) and 28 days after each injection)
- Percentage of Participants With a Detected and Quantified CYD Dengue Vaccinal Viremia(At 7 and 14 days post-injection 1)
- Percentage of Participants With Confirmed Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Viral Load Increase(From Day 28 to Day 393 (28 days after each injection))
- Percentage of Participants With Clusters of Differentiation 4 (CD4) Count Decrease(From Day 28 to Day 393 (28 days after each injection))