A Phase III, Randomized, Double-blind, Placebo-controlled Multi-country Study to Demonstrate Efficacy of a Single Dose of Unadjuvanted RSV Maternal Vaccine, Administered IM to Pregnant Women 18 to 49 Years of Age, for Prevention of RSV Associated LRTIs in Their Infants up to 6 Months of Age
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 10,578
- 试验地点
- 1
- 主要终点
- Number of Infant Participants With Medically Assessed, RSV-associated Lower Respiratory Tract Illnesses (LRTIs) of Any Severity and RSV-associated Severe LRTIs From Birth to Day 181 Post-birth
研究概览
简要总结
The purpose of this study is to evaluate the ability of a single dose of the investigational RSV Maternal vaccine, administered intramuscularly (IM) to pregnant women aged 18-49 years, in good general maternal health, in preventing medically assessed RSV associated Lower Respiratory Tract Illnesses (LRTIs) in infants born to vaccinated mothers. The study will also evaluate the safety of the investigational RSV Maternal vaccine both in vaccinated mothers and in their corresponding infant.
Following a recommendation from the Independent Data Monitoring Committee of NCT04605159 (RSV MAT 009), GSK made the decision to stop enrolment and vaccination in the study. Ongoing study participants will continue to be monitored as part of the study.
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)
盲法说明
Following the decision to stop enrollment and vaccination, the study/site staff and maternal participants no longer stay blinded.
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Maternal participants
- •Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
- •Participants who give written or witnessed/thumb printed informed consent after the study has been explained, and before any study specific procedures are performed, as per local regulations regulatory requirements.
- •Age 18 to 49 years, inclusive, at the time of study intervention.
- •Pre-pregnancy BMI 17.0 to 39.9 kg/m2, inclusive.
- •In good general maternal health as established by medical history and clinical examination before entering into the study.
- •Singleton pregnancy (including instances where the singleton pregnancy derives from a vanishing twin syndrome).
- •At 24^0/7 to 34^0/7 weeks of gestation at the time of study vaccination (Visit 1), as established by:
- •last menstrual period (LMP) date corroborated by first or second trimester ultrasound examination (U/S) i.e. at or before 28 weeks of gestation.
- •1st or 2nd trimester U/S only, if LMP is unknown/uncertain
- •Certain LMP, corroborated by an U/S performed after 28 weeks of gestation is also acceptable.
- •No fetal genetic abnormalities (based on genetic testing, if performed).
- •No significant congenital malformations, as assessed by fetal anomaly ultrasound scan conducted at or beyond 18 weeks of gestation.
- •Willing to provide cord blood.
- •Who do not plan to give their child for adoption.
- •Who plan to reside in the study area for at least one year after delivery.
- •Willing to have the infant followed-up after delivery for a period of 12 months.
- •Infant participants
- •Live-born from the study pregnancy.
- •If required per local regulations/guidelines, re-signed (confirmed) written or witnessed/thumb printed informed consent for study participation of the infant obtained from the infant's mother and/or father and/or LAR, before performing any study specific procedure. OR, if permitted by local regulation, documented verbal consent for infant's participation obtained from the parent(s)/LAR(s) at birth, followed by written consent obtained by (or before) Visit 2-newborn.
排除标准
- •Maternal participants Medical conditions
- •History of allergic disease or reactions likely to be exacerbated by any component of the RSV vaccine
- •Hypersensitivity to latex
- •Significant complications in the current pregnancy:
- •Gestational hypertension unless blood pressure it is controlled and maintained in the normal range (<140mmHg and <90mmHg) through diet and/or antihypertensive medications
- •Gestational diabetes not controlled by medication, diet and/or exercise
- •Pre-eclampsia
- •Eclampsia
- •Intrauterine Growth Restriction/Fetal Growth Restriction
- •Placenta previa
- •Placental abruption, placenta accreta/percreta/increta, chorioamnionitis or any abnormalities that can impair the maternal-fetal circulation
- •Polyhydramnios
- •Oligohydramnios
- •Preterm labour or history of preterm labour in the current pregnancy
- •Any intervention to prevent preterm delivery or medical treatment for suspected preterm delivery, including administration of systemic corticosteroids for fetal lung maturation
- •Cholestasis
- •Other pregnancy-related complications (per investigator's judgement)
- •Significant structural abnormalities of the uterus or cervix
- •History of 2 or more prior stillbirths or neonatal deaths/history of 2 or more preterm births at ≤34 weeks gestation/3 or more consecutive spontaneous abortions
- •Known HIV infection (as per serological tests performed during the current pregnancy)
- •Known or suspected HBV or HCV infection
- •Known or suspected infection during the current pregnancy with Toxoplasma, Parvovirus B19, Syphilis, Zika, Rubella, Varicella, CMV or primary genital Herpes Simplex
- •Active infection with tuberculosis
- •Known or suspected impairment of the immune system
- •Current autoimmune disorder for which the participant has received immune-modifying therapy within 6 months before study vaccination, or plans administration through delivery
- •Lymphoproliferative disorder or malignancy within 5 years before study vaccination
- •Acute or chronic clinically significant abnormality or poorly controlled pre-existent co-morbidities or any other clinical conditions that might pose additional risk to the participant due to participation in the study
- •Any conditions that may interfere with participant's ability to comply with study procedures or receipt of prenatal care
- •Any condition which would increase the risks of study participation to the unborn infant
- •Prior/Concomitant therapy
- •Prior receipt of an RSV vaccine in the current pregnancy
- •Use of any investigational/non-registered product other than the study vaccine/product as described below, or planned use during the period :
- •For a drug, vaccine or medical device: from 29 days before the dose of study vaccine
- •For immunoglobulins: 3 months before the dose of study vaccine/product.
- •The exception to this is investigational products administered in the setting of a pandemic which may be allowed following delivery
- •Planned administration/administration of any vaccine from 29 days before the dose of study vaccine or planned administration through delivery, except:
- •Seasonal influenza vaccines, tetanus vaccines, dTpa/Tdap - alone vaccines, dTpa/Tdap vaccines that also contain other antigens, Hepatitis B vaccines, and COVID-19 vaccines all of which may be administered according to standard of care ≥15 days before or after study vaccination
- •Administration of immunoglobulins (except anti-Rh0D IG, which may be administered at any time), blood products or plasma derivatives within 3 months before study vaccination or planned administration through delivery
- •Administration of immune-modifying therapy within 6 months before the study vaccination, or planned administration through delivery. This includes but is not limited to:
- •Azathioprine, mycophenolate mofetil, 6-mercaptopurine, cyclosporine, tacrolimus, monoclonal or polyclonal antibodies
- •Prednisone ≥5 mg/day or equivalent for ≥14 days; Inhaled, intra-articular/intra-bursal and topical steroids are allowed
- •Corticosteroids administered for fetal lung maturation
- •Prior/Concurrent clinical study experience
- •Concurrently participating in another clinical study, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product
- •Other exclusions
- •Alcoholism or substance use disorder within the past 24 months based on DSM-5 criteria
- •A local condition that precludes injection of the study vaccine/product or precludes assessment of local reactogenicity
- •Consanguinity of maternal participant and her partner (second degree cousins or closer)
- •Any study personnel or their immediate dependants, family or household members
- •Infant participants
- 另有 3 项未显示
研究组 & 干预措施
RSV MAT Group - Mother
Maternal participants received a single dose of the RSV MAT vaccine administered at Day 1 in this study.
干预措施: RSV MAT (Biological)
Placebo Group - Mother
Maternal participants received a single dose of placebo administered at Day 1 in this study.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Infant Participants With Medically Assessed, RSV-associated Lower Respiratory Tract Illnesses (LRTIs) of Any Severity and RSV-associated Severe LRTIs From Birth to Day 181 Post-birth
时间窗: From birth to Day 181 post-birth
An RSV-associated LRTI of any severity was characterized by a history of cough OR difficulty in breathing, AND a blood oxygen saturation by pulse oximetry (SpO2) lower than (\<) 95%, OR respiratory rate increase AND a confirmed RSV infection. An RSV-associated severe LRTI met the case definition of RSV-LRTI AND was additionally characterized by a SpO2 \<93%, OR lower chest wall in-drawing, OR inability to feed, OR failure to respond/unconscious. Medically assessed = the infant was evaluated by a healthcare professional for the LRTI.
Number of Infant Participants With at Least One Serious Adverse Event (SAE) From Birth to Day 181 Post-birth
时间窗: From birth to Day 181 post-birth
An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect or resulted in other situations that were considered serious per medical or scientific judgment. At least one SAE = occurrence of at least one SAE regardless of intensity grade or relation to vaccination.
Number of Infant Participants With at Least One Adverse Event (AE) Leading to Study Withdrawal From Birth to Day 181 Post-birth
时间窗: From birth to Day 181 post-birth
A participant was considered a 'withdrawal' from the study when no study procedure has occurred, no follow-up has been performed and no further information has been collected for this participant from the date of withdrawal/last contact. Participants who were withdrawn from the study because of AEs were clearly distinguished from participants who were withdrawn for other reasons. Investigators followed participants who were withdrawn from the study as a result of an AE until the event was resolved. At least one AE leading to study withdrawal = occurrence of at least one AE leading to study withdrawal regardless of intensity grade or relation to vaccination.
Number of Infant Participants With at Least One Medically Attended AE (MAE) From Birth to Day 181 Post-birth
时间窗: From birth to Day 181 post-birth
An MAE is defined as an unsolicited AE, such as a symptom or illness, which required hospitalization, or emergency room visit, or visit to/by a health care provider. At least one MAE = occurrence of at least one MAE regardless of intensity grade or relation to vaccination.
Number of Infant Participants With at Least One SAE From Birth to Day 366 Post-birth
时间窗: From birth to Day 366 post-birth
An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect or resulted in other situations that were considered serious per medical or scientific judgment. At least one SAE = occurrence of at least one SAE regardless of intensity grade or relation to vaccination.
Number of Infant Participants With at Least One AE Leading to Study Withdrawal From Birth to Day 366 Post-birth
时间窗: From birth to Day 366 post-birth
A participant was considered a 'withdrawal' from the study when no study procedure has occurred, no follow-up has been performed and no further information has been collected for this participant from the date of withdrawal/last contact. Participants who were withdrawn from the study because of AEs were clearly distinguished from participants who were withdrawn for other reasons. Investigators followed participants who were withdrawn from the study as a result of an AE until the event was resolved. At least one AE leading to study withdrawal = occurrence of at least one AE leading to study withdrawal regardless of intensity grade or relation to vaccination.
Number of Infant Participants With at Least One MAE From Birth to Day 366 Post-birth
时间窗: From birth to Day 366 post-birth
An MAE is defined as an unsolicited AE, such as a symptom or illness, which required hospitalization, or emergency room visit, or visit to/by a health care provider. At least one MAE = occurrence of at least one MAE regardless of intensity grade or relation to vaccination.
次要结局
- Number of Infant Participants With RSV-associated Hospitalizations From Birth to Day 181 Post-birth(From birth to Day 181 post-birth)
- Number of Infant Participants With All-cause LRTIs From Birth to Day 181 Post-birth(From birth to Day 181 post-birth)
- Number of Infant Participants With All-cause LRTIs With Hospitalization From Birth to Day 181 Post-birth(From birth to Day 181 post-birth)
- Number of Infant Participants With Medically Assessed, RSV-associated Severe LRTIs From Birth to Day 366 Post-birth(From birth to Day 366 post-birth)
- Number of Infant Participants With Medically Assessed, RSV-associated LRTIs of Any Severity From Birth to Day 366 Post-birth(From birth to Day 366 post-birth)
- Number of Infant Participants With Medically Assessed, RSV-associated Severe LRTIs for RSV Subtype A and RSV Subtype B Separately From Birth to Day 181 Post-birth(From birth to Day 181 post-birth)
- Number of Infant Participants With Medically Assessed, RSV-associated LRTIs of Any Severity for RSV Subtype A and RSV Subtype B Separately From Birth to Day 181 Post-birth(From birth to Day 181 post-birth)
- Number of Infant Participants With Medically Assessed, RSV-associated Severe LRTIs From Birth to Day 121 Post-birth(From birth to Day 121 post-birth)
- Number of Infant Participants With Medically Assessed, RSV-associated LRTIs of Any Severity From Birth to Day 121 Post-birth(From birth to Day 121 post-birth)
- Number of Infant Participants With All-cause Pneumonia From Birth to Day 181 Post-birth(From birth to Day 181 post-birth)
- Number of Infant Participants With RSV-associated Hospitalizations From Birth to Day 366 Post-birth(From birth to Day 366 post-birth)
- Number of Maternal Participants With RSV-associated Medically Attended RTIs (RSV-MA-RTIs) From Study Intervention Administration (Day 1) to Day 181 Post-delivery(From study intervention administration (Day 1) to Day 181 post-delivery)
- RSV-A Neutralizing Antibody Titers for Maternal Participants at Day 1, at Day 31 and at Delivery(At Day 1 (before study intervention administration), at Day 31 and at delivery)
- RSV-A Neutralizing Antibody Titers for Infant Participants at Delivery or Within 72 Hours After Birth(At delivery or within 72 hours after birth)
- RSV-A Neutralizing Antibody Titers for Infant Participants at Day 43 Post-birth(At Day 43 post-birth)
- RSV-A Neutralizing Antibody Titers for Infant Participants at Day 121 Post-birth(At Day 121 post-birth)
- RSV-A Neutralizing Antibody Titers for Infant Participants at Day 181 Post-birth(At Day 181 post-birth)
- RSV MAT Immunoglobulin G (IgG)-Specific Antibody Concentrations for Maternal Participants at Delivery(At delivery)
- RSV MAT IgG-specific Antibody Concentrations for Infant Participants at Delivery or Within 72 Hours After Birth(At delivery or within 72 hours after birth (only if no cord blood sample could be obtained at delivery))
- Geometric Mean Ratio (GMR) Between Cord Blood and Maternal RSV MAT Immunoglobulin G (IgG)-Specific Antibody Concentrations(At delivery (for maternal participants) or within 72 hours after birth (for infant participants, only if no cord blood could be obtained))
- Number of Maternal Participants With Any Solicited Administration Site Events From Day 1 to Day 7 Included(From Day 1 to Day 7 included)
- Number of Maternal Participants With Any Solicited Systemic Events From Day 1 to Day 7 Included(From Day 1 to Day 7 included)
- Number of Maternal Participants With Any Unsolicited AEs From Day 1 to Day 30 Included(From Day 1 to Day 30 included)
- Number of Maternal Participants With at Least One SAE From Day 1 to Day 181 Post-delivery(From Day 1 to Day 181 post-delivery)
- Number of Maternal Participants With at Least One AE Leading to Study Withdrawal From Day 1 to Day 181 Post-delivery(From Day 1 to Day 181 post-delivery)
- Number of Maternal Participants With at Least One All-cause MA-RTI From Day 1 to Day 181 Post-delivery(From Day 1 to Day 181 post-delivery)
- Number of Maternal Participants With at Least One MAE From Day 1 to Day 42 Post-delivery(From Day 1 to Day 42 post-delivery, an average of 2 months)
- Number of Maternal Participants With Pregnancy Outcomes From Day 1 to Day 42 Post-delivery(From Day 1 to Day 42 post-delivery, an average of 2 months)
- Number of Maternal Participants With Pregnancy-related Adverse Events of Special Interest (AESIs) From Day 1 to Day 42 Post-delivery(From Day 1 to Day 42 post-delivery, an average of 2 months)
- Number of Infant Participants With Neonatal AESIs From Birth to Day 42 Post-birth(From birth to Day 42 post-birth, an average of 2 months)