A Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy.
- Conditions
- Respiratory Tract Infection
- Interventions
- Biological: Placebo
- Registration Number
- NCT04424316
- Lead Sponsor
- Pfizer
- Brief Summary
This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate the efficacy and safety of maternal immunization with RSVpreF against medically attended lower respiratory tract illness (MA-LRTI) in infants.
- Detailed Description
This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to assess the efficacy, safety, and immunogenicity of RSVpreF or placebo (1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well as the safety and immunogenicity in the pregnant women. This will be a global study which will span multiple RSV seasons.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 14727
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RSVpreF vaccine RSVpreF RSVpreF Placebo dose Placebo Placebo
- Primary Outcome Measures
Name Time Method Percentage of Infant Participants With Neonatal Deaths (Safety) Within 1 Month after birth Neonatal death was defined as the death of a live-born infant that occurred within a month after birth.
Percentage of Infant Participants With Medically Attended Lower Respiratory Tract Illness (MA-LRTI) Cases Due to RSV Occurring Within 90 Days After Birth (Efficacy) Within 90 days after birth Results are presented as confirmed by endpoint adjudication committee. MA-LRTI case: infant with an MA-RTI visit with age related fast breathing (respiratory rate \[RR\] more than or equal to \[\>=\] 60 breaths per minute \[bpm\] for less than \[\<\] 2 months of age \[\<60 days of age\], \>=50 bpm for \>=2 months to \<12 months of age, or \>=40 bpm for \>=12 months to 24 months of age) or oxygen saturation (SpO2) \<95 percent (%) or chest wall indrawing and RSV positive test results by reverse transcription-polymerase chain reaction (RT-PCR) testing of midturbinate nasal swab samples.
Percentage of Infant Participants With MA-LRTI Cases Due to RSV Occurring Within 120 Days After Birth (Efficacy) Within 120 days after birth Results are presented as confirmed by endpoint adjudication committee. MA-LRTI case: Infant with an MA-RTI visit with age related fast breathing (RR \>=60 bpm for \<2 months of age \[\<60 days of age\], \>=50 bpm for \>=2 months to \<12 months of age, or \>=40 bpm for \>=12 months to 24 months of age) or SpO2 \<95% or chest wall indrawing and RSV positive test results by RT-PCR testing of midturbinate nasal swab samples.
Percentage of Infant Participants With MA-LRTI Cases Due to RSV Occurring Within 150 Days After Birth (Efficacy) Within 150 days after birth Results are presented as confirmed by endpoint adjudication committee. MA-LRTI case: Infant with an MA-RTI visit with age related fast breathing (RR \>=60 bpm for \<2 months of age \[\<60 days of age\], \>=50 bpm for \>=2 months to \<12 months of age, or \>=40 bpm for \>=12 months to 24 months of age) or SpO2 \<95% or chest wall indrawing and RSV positive test results by RT-PCR testing of midturbinate nasal swab samples.
Percentage of Infant Participants With MA-LRTI Cases Due to RSV Occurring Within 180 Days After Birth (Efficacy) Within 180 days after birth Results are presented as confirmed by endpoint adjudication committee. MA-LRTI case: Infant with an MA-RTI visit with age related fast breathing (RR \>=60 bpm for \<2 months of age \[\<60 days of age\], \>=50 bpm for \>=2 months to \<12 months of age, or \>=40 bpm for \>=12 months to 24 months of age) or SpO2 \<95% or chest wall indrawing and RSV positive test results by RT-PCR testing of midturbinate nasal swab samples.
Percentage of Infant Participants With Severe MA-LRTI Cases Due to RSV Occurring Within 90 Days After Birth (Efficacy) Within 90 days after birth Results are presented as confirmed by endpoint adjudication committee. Severe MA-LRTI cases were a subset of MA-LRTI cases, and all severe MA-LRTI cases included MA-LRTI cases. Severe MA-LRTI case was an RSV positively adjudicated event which met the following defined criteria: an infant with an MA-RTI visit and aged associated fast breathing (RR \>=70 bpm for \<2 months of age \[\<60 days of age\], \>=60 bpm for \>=2 months to \<12 months of age, or \>=50 bpm for \>=12 months to 24 months of age) or SpO2 \<93% or high-flow nasal cannula or mechanical ventilation (i.e., invasive or non-invasive) or intensive care unit (ICU) admission for more than (\>) 4 hours or failure to respond/unconscious.
Percentage of Infant Participants With Severe MA-LRTI Cases Due to RSV Occurring Within 120 Days After Birth (Efficacy) Within 120 days after birth Results are presented as confirmed by endpoint adjudication committee. Severe MA-LRTI cases were a subset of MA-LRTI cases, and all severe MA-LRTI cases were included MA-LRTI cases. Severe MA-LRTI case was an RSV positively adjudicated event which met the following defined criteria: an infant with an MA-RTI visit and aged associated fast breathing (RR \>=70 bpm for \<2 months of age \[\<60 days of age\], \>=60 bpm for \>=2 months to \<12 months of age, or \>=50 bpm for \>=12 months to 24 months of age) or SpO2 \<93% or high-flow nasal cannula or mechanical ventilation (i.e., invasive or non-invasive) or ICU admission for \>4 hours or failure to respond/unconscious.
Percentage of Infant Participants With Severe MA-LRTI Cases Due to RSV Occurring Within 150 Days After Birth (Efficacy) Within 150 days after birth Results are presented as confirmed by endpoint adjudication committee. Severe MA-LRTI cases were a subset of MA-LRTI cases, and all severe MA-LRTI cases were included MA-LRTI cases. Severe MA-LRTI case was an RSV positively adjudicated event which met the following defined criteria: an infant with an MA-RTI visit and aged associated fast breathing (RR \>=70 bpm for \<2 months of age \[\<60 days of age\], \>=60 bpm for \>=2 months to \<12 months of age, or \>=50 bpm for \>=12 months to 24 months of age) or SpO2 \<93% or high-flow nasal cannula or mechanical ventilation (i.e., invasive or non-invasive) or ICU admission for \>4 hours or failure to respond/unconscious.
Percentage of Infant Participants With Congenital Malformations/Anomalies (Safety) 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.
Percentage of Infant Participants With Severe MA-LRTI Cases Due to RSV Occurring Within 180 Days After Birth (Efficacy) Within 180 days after birth Results are presented as confirmed by endpoint adjudication committee. Severe MA-LRTI cases were a subset of MA-LRTI cases, and all severe MA-LRTI cases were included MA-LRTI cases. Severe MA-LRTI case was an RSV positively adjudicated event which met the following defined criteria: an infant with an MA-RTI visit and aged associated fast breathing (RR \>=70 bpm for \<2 months of age \[\<60 days of age\], \>=60 bpm for \>=2 months to \<12 months of age, or \>=50 bpm for \>=12 months to 24 months of age) or SpO2 \<93% or high-flow nasal cannula or mechanical ventilation (i.e., invasive or non-invasive) or ICU admission for \>4 hours or failure to respond/unconscious.
Percentage of Infant Participants With Other Neonatal Events (Safety) Within 1 Month after birth Other Neonatal problem included dysmaturity, neonatal illness, hospitalization, drug therapies, and neonatal death.
Number of Infant Participants According to APGAR Score at 5 Minutes After Birth (Safety) 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 Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) Score at 1 Minute After Birth (Safety) 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 10 Minutes After Birth (Safety) 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.
Percentage of Infant Participants With Adverse Events (AEs) From Birth to 1 Month of Age (Safety) 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 Serious Adverse Events (SAEs) and Newly Diagnosed Chronic Medical Conditions (NDCMCs) From Birth Through 6 Months of Age (Safety) 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. 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.
Percentage of Infant Participants With SAEs and NDCMCs From Birth Through 12 Months of Age (Safety) From birth to 12 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. 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.
Percentage of Infant Participants With SAEs and NDCMCs From Birth Through 24 Months of Age (Safety) From birth to 24 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. 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.
Percentage of Maternal Participants With Prespecified Local Reactions Within 7 Days After Vaccination (Safety) 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 and recorded in measuring device units. 1 measuring device unit= 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 the severe pain at the injection site). Grade 4 reactions were classified by the investigator or medically qualified person.
Percentage of Maternal Participants With Prespecified Systemic Events Within 7 Days After Vaccination (Safety) 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 an e-diary. Fever was defined as an oral temperature \>=38.0 degree Celsius \[C\]) and classified as mild (38.0 to 38.4), moderate (38.5 to 38.9), severe (39.0 to 40.0) 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 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 person.
Percentage of Maternal Participants With AEs From the Time of Vaccination Through 1 Month After Vaccination (Safety) 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 SAEs Throughout the Study Period (Safety) From vaccination on Day 1 up to 6 months after delivery (maximum up to 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 Adverse Events of Special Interest (AESI) (Safety) From birth to 24 months of age AESI 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 and their infants prior to/during delivery and at birth. For infant participants the following were considered as protocol defined AESIs: Preterm birth (born at \<37 weeks gestation); birth weight 1001-2500 grams; developmental delay; positive viral (polymerase chain reaction \[PCR\] or antigen-based) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when not reported during MA-RTI visit, were reported as SARS-CoV-2 test positive. Extremely preterm birth (\<28 weeks) and extremely low birth weight (=\<1000 grams \[g\]) were reported as serious AESIs.
- Secondary Outcome Measures
Name Time Method Percentage of Infant Participants With Cases of Hospitalization Due to RSV Within 90, 120, 150, 180 and 360 Days After Birth (Efficacy) Within 90, 120, 150, 180 and 360 days after birth Results are reported as confirmed by endpoint adjudication committee.
Percentage of Infant Participants With MA-LRTI Cases Due to Any Cause With Protocol Defined Criteria Occurring Within 90, 120, 150, 180 and 360 Days After Birth (Efficacy) Within 90, 120, 150, 180 and 360 days after birth MA-LRTI cases due to any cause was defined as an infant with a MA-RTI visit with age related fast breathing (RR \>=60 bpm for \<2 months of age \[\<60 days of age\], \>=50 bpm for \>=2 months to \<12 months of age, or \>=40 bpm for \>=12 months to 24 months of age) or SpO2 \<95% or chest wall indrawing.
Percentage of Infant Participants With MA-LRTI Cases Due to RSV Occurring Within 210, 240, 270 and 360 Days After Birth (Efficacy) Within 210, 240, 270 and 360 days after birth Results are presented as confirmed by endpoint adjudication committee. MA-LRTI case: Infant with an MA-RTI visit with age related fast breathing (RR \>=60 bpm for \<2 months of age \[\<60 days of age\], \>=50 bpm for \>=2 months to \<12 months of age, or \>=40 bpm for \>=12 months to 24 months of age) or SpO2 \<95% or chest wall indrawing and RSV positive test results by RT-PCR testing of midturbinate nasal swab samples.
Related Research Topics
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Trial Locations
- Locations (436)
Central Research Associates, Inc.
🇺🇸Birmingham, Alabama, United States
Endocrinology and Internal Medicine Associates, PC
🇺🇸Birmingham, Alabama, United States
OB/GYN Associates of Alabama, PC
🇺🇸Birmingham, Alabama, United States
Sharp and Stone OB/GYN PC
🇺🇸Birmingham, Alabama, United States
St Vincent's Hospital
🇺🇸Birmingham, Alabama, United States
Children's of Alabama
🇺🇸Birmingham, Alabama, United States
UAB Women & Infants Center - UAB Medicine
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham/Center for Women's Reproductive Health
🇺🇸Birmingham, Alabama, United States
Cullman Clinical Research, Inc
🇺🇸Cullman, Alabama, United States
Cullman Primary Care, PC
🇺🇸Cullman, Alabama, United States
Scroll for more (426 remaining)Central Research Associates, Inc.🇺🇸Birmingham, Alabama, United States