A PHASE 3 STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A RESPIRATORY SYNCYTIAL VIRUS VACCINE IN CHILDREN AT HIGH RISK OF RSV DISEASE
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- Pfizer
- 入组人数
- 920
- 试验地点
- 2
- 主要终点
- Cohort 1: Proportion of participants reporting pre-specified local reactions within 7 days following investigational product administration
研究概览
简要总结
The purpose of the study is to evaluate the safety, tolerability, and immunogenicity of RSVpreF in children 5 to <18 years of age at high risk for RSV disease, including those who are immunocompromised.
详细描述
The study will first enroll immunocompetent, RSV-experienced participants before enrolling immunocompromised participants to allow for safety data review. Both Cohorts 1 (chronic conditions) and 2 (immunocompromising conditions) will be stratified into 2 age strata. Cohort 1a will enroll participants 12 to <18 years of age with chronic medical conditions and Cohort 1b will enroll participants 5 to <12 years of age with chronic medical conditions. Cohort 2a will enroll immunocompromised participants 12 to <18 years of age and Cohort 2b will enroll immunocompromised participants 5 to <12 years of age.
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
- Double (Participant, Investigator)
盲法说明
Double-blinded, placebo-controlled
入排标准
- 年龄范围
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants' age requirements for each study cohort at enrollment, respectively Cohort 1a (chronic medical conditions) 12 to <18 years of age Cohort 1b (chronic medical conditions) 5 to <12 years of age Cohort 2a (immunocompromising conditions) 12 to <18 years of age Cohort 2b (immunocompromising conditions) 5 to <12 years of age
- •Participants depending on the study cohort requirements, will be considered by the investigator to be at high risk of LRTI-RSV based on the following disease characteristics and definitions:
- •Chronic medical conditions:
- •Cystic fibrosis
- •Medically treated asthma
- •Other chronic respiratory diseases and malformations of the lung
- •Trisomy 21 (Down syndrome)
- •Neuromuscular disease
- •Cerebral palsy
- •Hemodynamically significant or symptomatic congenital heart disease
- •Sickle cell disease
- •Confirmed stable HIV disease defined as documented viral load <50 copies/mL and CD4 count >200 cells/mm3 within 6 months before enrollment, and on stable antiretroviral therapy for at least 6 months
- •Immunocompromising conditions:
- •Immunomodulatory therapy: Is on an active immunosuppressive (including cytotoxic) or immunomodulatory therapy at a stable dose. Patients taking steroids as monotherapy must be on a dose of at least 2 mg/kg/day or 20 mg/day or greater OR
- •Primary immune deficiency: Has a diagnosed primary immunodeficiency disease OR
- •Cellular therapy: Has received a bone marrow or stem cell transplant at least 6 months (180 days) prior to enrollment with adequate immune reconstitution for immunization in the investigator's opinion or has received chimeric antigen receptor T cell (CAR-T) therapy more than 90 days prior to enrollment OR
- •Solid organ transplant: Has received a solid organ transplant at least 3 months prior and with no acute rejection episodes within 90 days prior to enrollment and is on ongoing immunosuppressive therapy OR
- •End-stage renal disease: Has end-stage renal disease (ESRD) on hemodialysis (HD)
- •Participants' weight must be:
- •Cohort 1a: ≥30.0 kg at enrollment Cohort 1b: ≥14.5 kg at enrollment Cohort 2a : ≥30 kg at enrollment Cohort 2b: ≥14.5 kg at enrollment
- •The participant's parent(s)/legal guardian is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in the protocol. Depending on the age of the participant and according to local requirements, participants will also be asked to provide assent as appropriate (verbal or written)
排除标准
- •Applicable to Cohort 1 (a and b) participants only: Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination
- •Applicable to Cohort 1 (a and b) participants only: Individuals with a history of autoimmune disease, past or present, requiring therapeutic intervention including, but not limited to, systemic lupus erythematosus. Note: Stable type 1 diabetes and hypothyroidism are permitted
- •History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s)
- •Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection
- •Individuals with epilepsy or other seizure disorders that is uncontrolled/unstable, or a history of seizures and/or other neurological complications following vaccination
- •History of Guillain-Barré syndrome and/or acute polyneuropathy without an underlying etiology.
- •Individuals who are pregnant
- •Any medical or psychiatric condition, including any active suicidal ideation in the past year or suicidal behavior in the past 5 years or laboratory abnormality, that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study
研究组 & 干预措施
Cohort 1: Placebo
Cohort 1 (a and b): Participants will receive a single dose of placebo at the first study visit.
干预措施: Placebo (Biological)
Cohort 2: RSVpreF/Placebo
Cohort 2 (a and b): Participants will receive 1 dose of RSVpreF at the first study visit, and 1 dose of placebo at the 12-month visit.
干预措施: Placebo (Biological)
Cohort 2: RSVpreF/RSVpreF
Cohort 2 (a and b): Participants will receive 1 dose of RSVpreF at the first study visit, and 1 dose of RSVpreF at the 12-month visit.
干预措施: RSVpreF (Biological)
Cohort 1: RSVpreF
Cohort 1 (a and b): Participants will receive a single dose of RSVpreF at the first study visit.
干预措施: RSVpreF (Biological)
Cohort 2: RSVpreF/Placebo
Cohort 2 (a and b): Participants will receive 1 dose of RSVpreF at the first study visit, and 1 dose of placebo at the 12-month visit.
干预措施: RSVpreF (Biological)
结局指标
主要结局
Cohort 1: Proportion of participants reporting pre-specified local reactions within 7 days following investigational product administration
时间窗: Within 7 days
Describe pre-specified local reactions in children 5 to \<18 years of age with chronic medical conditions
Cohort 2: Proportion of participants reporting pre-specified local reactions within 7 days following each investigational product administration
时间窗: Within 7 days
Describe pre-specified local reactions in children 5 to \<18 years of age with immunocompromising conditions
Cohort 1: Proportion of participants reporting pre-specified systemic events within 7 days following investigational product administration
时间窗: Within 7 days
Describe pre-specified systemic events in children 5 to \<18 years of age with chronic medical conditions
Cohort 2: Proportion of participants reporting pre-specified systemic events within 7 days following each investigational product administration
时间窗: Within 7 days
Describe pre-specified systemic events in children 5 to \<18 years of age with immunocompromising conditions
Cohort 1: Proportion of participants reporting adverse events (AEs) through 1 month following investigational product administration
时间窗: From vaccination through 1 month after vaccination
Describe AEs in children 5 to \<18 years of age with chronic medical conditions
Cohort 2: Proportion of participants reporting adverse events (AEs) through 1 month following last investigational product administration
时间窗: From vaccination through 1 month after last vaccination
Describe AEs in children 5 to \<18 years of age with immunocompromising conditions
Cohort 1: Proportion of participants reporting serious adverse events (SAEs) throughout the study
时间窗: From vaccination through 24 months after vaccination
Describe SAEs in children 5 to \<18 years of age with chronic medical conditions
Cohort 2: Proportion of participants reporting serious adverse events (SAEs) throughout the study
时间窗: From vaccination through 12 months after last vaccination
Describe SAEs in children 5 to \<18 years of age with immunocompromising conditions
Cohort 1: Proportion of participants reporting newly diagnosed chronic medical conditions (NDCMCs) throughout the study
时间窗: From vaccination through 24 months after vaccination
Describe NDCMCs in children 5 to \<18 years of age with chronic medical conditions
Cohort 2: Proportion of participants reporting newly diagnosed chronic medical conditions (NDCMCs) throughout the study
时间窗: From vaccination through 12 months after last vaccination
Describe NDCMCs in children 5 to \<18 years of age with immunocompromising conditions
Cohort 1: Geometric mean ratio (GMR), estimated by the ratio of the geometric mean titers (GMTs) for RSV A and RSV B serum neutralizing titers (NTs) 1 month after vaccination in participants in Study C3671017 Cohort 1 compared to those in Study C3671013
时间窗: 1 month after vaccination
Demonstrate that the immune responses elicited by RSVpreF in children 5 to \<18 years of age with chronic medical conditions are noninferior to the immune responses in adults ≥60 years of age
Cohort 1: Seroresponse rate of RSV A and RSV B serum NTs at 1 month after vaccination
时间窗: 1 month after vaccination
Demonstrate that the immune responses elicited by RSVpreF in children 5 to \<18 years of age with chronic medical conditions are noninferior to the immune responses in adults ≥60 years of age. Seroresponse is defined as a postvaccination NT ≥4 times the lower limit of quantitation (LLOQ) if the prevaccination titer is below the LLOQ; or a ≥4-fold rise from prevaccination if the prevaccination titer is ≥ LLOQ
Cohort 2: Neutralizing Titers (NTs) for RSV A and RSV B expressed as Geometric Mean Titers (GMT)
时间窗: Before each vaccination, 1 month after each vaccination, 12 months after last vaccination
Describe the immune responses elicited by 1 or 2 doses of RSVpreF in children 5 to \<18 years of age with immunocompromising conditions
Cohort 2: NTs for RSV A and RSV B expressed as Geometric Mean Fold Rise (GMFR)
时间窗: 1 month after each vaccination, 12 months after last vaccination
Describe the immune responses elicited by 1 or 2 doses of RSVpreF in children 5 to \<18 years of age with immunocompromising conditions
Cohort 2: NTs for RSV A and RSV B expressed as seroresponse rate
时间窗: 1 month after each vaccination, 12 months after last vaccination
Describe the immune responses elicited by 1 or 2 doses of RSVpreF in children 5 to \<18 years of age with immunocompromising conditions
次要结局
- Cohort 1: NTs for RSV A and RSV B expressed as Geometric Mean Titers (GMT)(Before vaccination, 1 month after vaccination, 12 months after vaccination, 24 months after vaccination)
- Cohort 1: NTs for RSV A and RSV B expressed as GMFR(1 month after vaccination, 12 months after vaccination, 24 months after vaccination)
- Cohort 1: NTs for RSV A and RSV B expressed as seroresponse rate(1 month after vaccination, 12 months after vaccination, 24 months after vaccination)