A PHASE 3, RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F SUBUNIT VACCINE IN PREGNANT PARTICIPANTS LIVING WITH HIV AND THEIR INFANTS
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 681
- 试验地点
- 28
- 主要终点
- Infant Participants Primary Safety - The proportion of participants reporting Specific Birth Outcomes
研究概览
简要总结
The purpose of the study is to learn about the safety and immune activity of the RSVpreF vaccine. It will be studied in infants born to mothers living with HIV. These infants may have higher chances of getting sick or dying due to RSV infection. Respiratory Syncytial Virus (RSV) is a common type of virus (germ) that can cause severe illness (airway diseases), where medical help is needed. Vaccines help your body make antibodies which help fight against diseases. The antibodies are substances your body uses to fight off an infection. The antibodies can be passed to the infant through the placenta of the mother.
The study will look at the safety, tolerability, and immune activity in mothers and their infants.
This study is seeking pregnant women who are:
- Less than or equal to 49 years old and have HIV (Human immunodeficiency virus -
- Receiving standard medical care during the pregnancy
- Do not have syphilis (bacterial sexually transmitted disease), Hepatitis B Virus ((HBV) liver infection), Tuberculosis ((TB) bacterial lung infection).
- Have been on stable (anti-retroviral) HIV treatment for more than or equal to 90 days.
- agree to be present for all study visits, procedures, and blood draws.
Participants will either receive:
- RSVpreF vaccine
- A placebo. A placebo does not have any medicine it but looks just like the study vaccine.
Pregnant participants will be involved in the study from:
- consent during their current pregnancy, and
- for 6 months after delivery of their baby (around 10 months in total). Pregnant participants will have at least 5 planned visits in this study. Infant participants: All eligible babies born to enrolled mothers will be followed up from birth for up to 6 months. Infant participants will have at least 3 study visits, with some site visits allowed to happen via home visits or over the telephone.
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
This is a double-blinded, placebo-controlled study
入排标准
- 年龄范围
- 0 Years 至 49 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Maternal Participants
- •Women ≤49 years of age who are between 24 0/7 and 36 0/7 weeks of gestation on the day of planned vaccination, with an uncomplicated singleton pregnancy who are at no known increased risk for complications.
- •Confirmed stable HIV disease.
- •Current and stable use of antiretroviral therapy(ART) for at least 90 days prior to enrolment.
- •Had a fetal anomaly ultrasound examination performed at ≥18 weeks of pregnancy with no significant fetal abnormalities observed.
- •Intention to deliver at a hospital or birthing facility where study procedures can be obtained.
- •Participant is willing to give informed consent for the participant's infant to participate in the study.
- •Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.
- •Key Inclusion Criteria - Infant Participants
- •Evidence of a signed and dated ICD, signed by the parent(s)/legal guardian(s).
- •Parent(s)/legal guardian(s) willing and able to comply with scheduled visits, investigational plan, laboratory tests, and other study procedures
排除标准
- •Maternal Participants
- •Prepregnancy body mass index (BMI) of >40 kg/m2 . If prepregnancy BMI is not available, the BMI at the time of the first obstetric visit during the current pregnancy may be used.
- •Participant with opportunistic infections or malignancy.
- •History of active chronic viral hepatitis with biochemical evidence of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values >5 times the upper limit of normal within 6 months before enrollment.
- •History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention or any related vaccine.
- •Current pregnancy resulting from in vitro fertilization. Participants known to have used clomiphene citrate and/or letrozole with or without intrauterine insemination (IUI) are permitted.
- •Current pregnancy complications or abnormalities at the time of consent that will increase the risk associated with the participation in and completion of the study, including but not l limited to the following:
- •Preeclampsia, eclampsia, or uncontrolled gestational hypertension.
- •Placental abnormality.
- •Polyhydramnios or oligohydramnios.
- •Significant bleeding or blood clotting disorder.
- •Endocrine disorders, including untreated hyperthyroidism or untreated hypothyroidism. This also includes disorders of glucose intolerance (eg, diabetes mellitus type 1 or 2) antedating pregnancy or occurring during pregnancy if uncontrolled at the time of consent.
- •Any signs of premature labor with the current pregnancy or having ongoing intervention (medical/surgical) in the current pregnancy to prevent preterm birth.
- •Prior pregnancy complications or abnormalities at the time of consent, based on the investigator's judgment, that will increase the risk associated with the participation in and completion of the study, including but not limited to the following:
- •Prior preterm delivery at ≤34 weeks' gestation
- •Prior stillbirth or neonatal death
- •Previous infant with a known genetic disorder or significant congenital anomaly
- •Non-HIV-associated congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other illness requiring chronic treatment with known immunosuppressant medications.
- •Antituberculosis treatment use currently or at any time during this current pregnancy.
- •Key Exclusion Criteria - Infant Participants
- •Infant who is a direct descendant (eg, child or grandchild) of the investigator site staff or sponsor and sponsor delegate employees directly involved in the conduct of the study.
研究组 & 干预措施
Placebo
Placebo
干预措施: Placebp (Biological)
RSVpreF vaccine
RSV vaccine (RSVpreF)
干预措施: RSVpreF vaccine (Biological)
结局指标
主要结局
Infant Participants Primary Safety - The proportion of participants reporting Specific Birth Outcomes
时间窗: Birth
Describe specific birth outcomes for infant participants
Maternal Participants Primary Safety - The proportion of participants reporting Adverse Event of Special Interests (AESIs)
时间窗: Throughout the study duration (approximately 10 months)
AESIs include preterm delivery, diagnosis of GB syndrome, Diagnosis of Acute polyneuropathy without underlying etiology, hypertensive disorders of pregnancy, atrial fibrillation.
Infant Participants Primary Safety - The proportion of participants reporting Adverse Events (AEs)
时间窗: Through 1 month following birth
An AE is any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs include both serious and non-serious adverse events.
Maternal Participants Primary Safety - The proportion of participants reporting systemic reactions
时间窗: Within 7 days following study administration intervention
Systemic Reactions: fever, fatigue, headache, nausea, muscle pain, joint pain, vomiting, diarrhea and any systemic event recorded based on e-diary and participant reported reactogenicity events.
Maternal Participants Primary Safety - The proportion of participants reporting local reactions
时间窗: Within 7 days following study administration intervention
Local reactions included pain at injection site, redness and swelling recorded based on e-diary and participant reported reactogenicity events.
Maternal Participants Primary Safety - The proportion of participants reporting Adverse Events (AEs)
时间窗: Through 1 month following study administration intervention
An adverse event was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. Adverse events included both serious and non-serious adverse events.
Maternal Participants Primary Safety - The proportion of participants reporting Serious Adverse Events (SAEs)
时间窗: Throughout the study duration (approximately 10 months)
SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Infant Participants Primary Safety - The proportion of participants reporting SAEs and Newly Diagnosed Chronic Medical Conditions (NDCMCs)
时间窗: Throughout the study duration (approximately 6 months)
SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. NDCMC is defined as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects.
Percentage of Maternal Participants With Prespecified Local Reactions Within 7 Days After Vaccination
时间窗: From Day 1 to Day 7 after vaccination
Local reactions included redness, swelling, and pain at injection site and were recorded in electronic diary (e-diary). Redness and swelling were measured by the maternal participant and recorded in measuring device units (mdu) in the e-diary (range: 1 to 21). 1 mdu = 0.5 centimetre (cm). Redness and swelling were graded as mild (\>2.0 to 5.0 cm), moderate (\>5.0 to 10.0 cm), severe (\>10.0 cm) and grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and grade 4 (emergency room visit or hospitalization for severe pain at the injection site). Grade 4 reactions were classified by the investigator or medically qualified designee.
Percentage of Maternal Participants With Prespecified Systemic Events Within 7 Days After Vaccination
时间窗: From Day 1 to Day 7 after vaccination
Systemic events included fever, fatigue, headache, nausea, muscle pain, joint pain, vomiting and diarrhea and were recorded by participants in the e-diary. Fever was defined as an oral temperature greater than or equal to (\>=) 38.0 degree Celsius (C) and classified as mild (38.0 to 38.4 degree C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C) and grade 4 (\>40.0 degree C). Headache, nausea, fatigue, muscle pain and joint pain were graded as mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily activity). Vomiting: mild (1-2 times in 24 hours \[H\]), moderate (\>2 times in 24 H), severe (required intravenous \[IV\] hydration). Diarrhea: mild (2-3 loose stools in 24 H), moderate (4-5 loose stools in 24 H), severe (\>=6 loose stools in 24 H). For all systemic events except fever, Grade 4= emergency room visit or hospitalization. Grade 4 events were classified by investigator or medically qualified designee.
Percentage of Maternal Participants With Adverse Events (AEs) From the Time of Vaccination Through 1 Month After Vaccination
时间窗: From vaccination on Day 1 up to 1 month after vaccination
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were included in this outcome measure.
Percentage of Maternal Participants With Adverse Event of Special Interest (AESIs)
时间窗: From vaccination on Day 1 up to 6 months after delivery (up to maximum of 10 months)
AESIs are a subset of targeted medical events based on review of known pharmacology, toxicology findings, possible class effects, published literature, and signals arising from safety data assessments, and on population under study. AESIs were based on targeted medical events associated with pregnant maternal participants prior to/during delivery and post delivery. For maternal participants, the following were considered as protocol defined AESIs: diagnosis of Guillain-Barré syndrome; diagnosis of acute polyneuropathy without an underlying etiology; hypertensive disorders of pregnancy; preterm delivery (delivery at \<37 0/7 weeks' gestation) and atrial fibrillation. AESIs was to be recorded as an AE or serious adverse event (SAE) on the case report form (CRF).
Percentage of Maternal Participants With SAEs From Vaccination Throughout the Study
时间窗: From vaccination on Day 1 up to 6 months after delivery (up to maximum of 10 months)
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was 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, resulted in congenital anomaly/birth defect or that was considered an important medical event.
Percentage of Infant Participants With AESIs From Birth Through 6 Months of Age
时间窗: From birth up to 6 months of age
AESIs are a subset of targeted medical events based on review of known pharmacology, toxicology findings, possible class effects, published literature, and signals arising from safety data assessments, and on population under study. AESIs were based on targeted medical events associated with infants at birth. For infant participants the following were considered as protocol defined AESIs: preterm birth (born at \<37 0/7 week's gestation); birth weight 1001-2500 grams (g); developmental delay. Extremely preterm birth (born at \<28 0/7 week's gestation) and extremely low birth weight (less than or equal to \[\<=\] 1000 g) were reported as serious AESIs.
Number of Infant Participants With Reported Neonatal Deaths From Birth Through 1 Months of Age
时间窗: Within 1 Month after birth
Neonatal death was defined as the death of a live-born infant that occurred within a month after birth.
Number of Infant Participants With Congenital Malformations/Anomalies at Birth
时间窗: At birth
Congenital malformations/anomalies were defined as structural or functional anomalies that occurred during intrauterine life and could be identified prenatally, at birth or later in life.
Number of Infant Participants With Other Neonatal Problems at Birth
时间窗: At birth
Other neonatal problem included dysmaturity, neonatal illness, hospitalization, and drug therapies.
Number of Infant Participants According to Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) Score at 1 Minute After Birth
时间窗: 1 minute after birth
APGAR was a fast evaluation technique used to evaluate a newborn baby's overall health. APGAR stands for (A) Appearance (skin coloration), (P) Pulse (heart rate), (G) Grimace (reflex response), (A) Activity (muscle tone) and (R) Respiration (breathing). Each component was given a score of 0, 1, or 2; after summing up scores for each component a total possible score was of 0 (worst condition) to 10 (best condition), where higher scores indicate better health. A score of 7 to 10 was good, 4 to \<7 was moderate, and \<4 was poor.
Number of Infant Participants According to APGAR Score at 5 Minutes After Birth
时间窗: 5 minutes after birth
APGAR was a fast evaluation technique used to evaluate a newborn baby's overall health. APGAR stands for (A) Appearance (skin coloration), (P) Pulse (heart rate), (G) Grimace (reflex response), (A) Activity (muscle tone) and (R) Respiration (breathing). Each component was given a score of 0, 1, or 2; after summing up scores for each component a total possible score was of 0 (worst condition) to 10 (best condition), where higher scores indicate better health. A score of 7 to 10 was good, 4 to \<7 was moderate, and \<4 was poor.
Number of Infant Participants According to APGAR Score at 10 Minutes After Birth
时间窗: 10 minutes after birth
APGAR was a fast evaluation technique used to evaluate a newborn baby's overall health. APGAR stands for (A) Appearance (skin coloration), (P) Pulse (heart rate), (G) Grimace (reflex response), (A) Activity (muscle tone) and (R) Respiration (breathing). Each component was given a score of 0, 1, or 2; after summing up scores for each component a total possible score was of 0 (worst condition) to 10 (best condition), where higher scores indicate better health. A score of 7 to 10 was good, 4 to \<7 was moderate, and \<4 was poor.
Number of Infant Participants According to Gestational Age (GA) at Birth
时间窗: At birth
GA at birth was collected as:\>=24 to \<28 weeks, \>=28 to \<34 weeks, \>=34 to \<37 weeks, \>=37 to \<42 weeks, and \>=42 weeks.
Number of Infant Participants Requiring Hospitalization at Birth
时间窗: From birth until discharge from hospitalization (up to a maximum of 72 hours)
Length of hospitalization at birth refers to the amount of time the infant remains admitted to the healthcare facility immediately following delivery and if that length of time is greater than or less than 72 hours. Postnatal standard of care procedures in South Africa were as follows: healthy newborns and their mothers were typically discharged within 24 hours after an uncomplicated vaginal delivery, or within 72 hours following an uncomplicated Caesarean section. These practices were supported by the Guidelines for Maternity Care in South Africa.
Percentage of Infant Participants With AEs From Birth to 1 Month of Age
时间窗: From birth to 1 month of age
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Percentage of Infant Participants With SAEs From Birth Through 6 Months of Age
时间窗: From birth to 6 months of age
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was 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, resulted in congenital anomaly/birth defect or that was considered an important medical event.
Percentage of Infant Participants With Newly Diagnosed Chronic Medical Conditions (NDCMCs) From Birth Through 6 Months of Age
时间窗: From birth to 6 months of age
An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or otherwise long-lasting in its effects. NDCMCs were reported as both AEs and SAEs.
次要结局
- Maternal Participants: Secondary Immunogenicity - GMT of NTs for RSV A and RSV B(Before vaccination and at the delivery visit)
- Maternal Participants: Secondary Immunogenicity - GMFR of NTs for RSV A and RSV B(From before vaccination and to the delivery visit)
- Geometric Mean Titer (GMT) of Neutralizing Titer (NTs) for Respiratory Syncytial Virus Subgroup A (RSV A) and Respiratory Syncytial Virus Subgroup B (RSV B) Before Vaccination and at Delivery: Maternal Participants(Before vaccination on Day 1 and at delivery)
- Geometric Mean Fold Rise (GMFR) of NTs for RSV A and RSV B From Before Vaccination to Delivery: Maternal Participants(Before vaccination on Day 1 to delivery)