A Study on the Safety and Immune Response to an Unadjuvanted RSV Maternal Vaccine, in High Risk Pregnant Women Aged 15 to 49 Years and Infants Born to the Vaccinated Mothers

• ClinicalTrials.gov Identifier: NCT04980391
• Recruitment Status: Terminated
• First Posted: July 28, 2021
• Results First Posted: February 6, 2024
• Last Update Posted: February 6, 2024
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

The purpose of this study was to evaluate the safety, reactogenicity and immune response of a single intramuscular dose of the respiratory syncytial virus (RSV) maternal vaccine compared to placebo, when administered in the second or third trimester of pregnancy in women, 15 to 49 years of age (YOA), with high risk pregnancies and in the infants born to the vaccinated mothers.

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 at that time continued to be monitored as part of the study.

Condition or disease	Intervention/treatment	Phase
Respiratory Syncytial Virus Infections	Biological: RSV MAT; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 384 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: The study was unblinded to ensure the participant's safety.
• Primary Purpose: Prevention
• Official Title: A Phase III, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety, Reactogenicity and Immune Response of a Single Intramuscular Dose of Unadjuvanted RSV Maternal Vaccine, in High Risk Pregnant Women Aged 15 to 49 Years and Infants Born to the Vaccinated Mothers
• Actual Study Start Date: August 3, 2021
• Actual Primary Completion Date: May 30, 2023
• Actual Study Completion Date: May 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: RSV_MAT Group; Maternal participants randomized to the RSV_MAT Group received a single dose of the RSV MAT vaccine administered, between 24 and 36 weeks of gestation, at Day 1 in this study.	Biological: RSV MAT; Single dose of the RSV MAT vaccine reconstituted with NaCl solution, administered intramuscularly in the non-dominant arm, at Day 1.
Placebo Comparator: Control Group; Maternal participants randomized to the Control Group received a single dose of Placebo administered, between 24 and 36 weeks of gestation, at Day 1 in this study.	Drug: Placebo; Single dose of placebo, administered intramuscularly in the non-dominant arm, at Day 1.
No Intervention: RSV_MAT Group-Infant; This group consisted of infants born to mothers (from RSV_MAT Group-Mother) who received a single dose of RSV MAT vaccine during pregnancy.
No Intervention: Control Group-Infant; This group consisted of infants born to mothers (from Control Group-Mother) who received a single dose of placebo during pregnancy.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Maternal Participants Reporting Any Solicited Administration Site Events [ Time Frame: From Day 1 to Day 7 included ]
   Assessed solicited administration site events included erythema, pain and swelling. Any pain = occurrence of the symptom regardless of intensity grade. Any erythema and swelling = symptom reported with a surface diameter greater than or equal to 20 millimeters.
2. Percentage of Maternal Participants Reporting Any Solicited Systemic Events [ Time Frame: From Day 1 to Day 7 included ]
   Assessed solicited systemic events included abdominal pain, diarrhea, fatigue, headache, nausea, fever [temperature equal to or above (>=) 38 degrees Celsius (°C)/100.4 degrees Fahrenheit (°F), regardless of the location of measurement] and vomiting. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination.
3. Percentage of Maternal Participants Reporting Any Unsolicited Adverse Events (AEs) [ Time Frame: From Day 1 to Day 30 included ]
   An unsolicited AE was defined as any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. Any = occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
4. Percentage of Maternal Participants Reporting Any Serious Adverse Events (SAEs) From Day 1 up to 42 Days Post-delivery [ Time Frame: From Day 1 up to 42 days post-delivery, an average of 2 months ]
   An SAE was 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 in the offspring of a study participant or resulted in abnormal pregnancy outcomes or in other situations that were considered serious per medical or scientific judgment. Any = occurrence of any SAE regardless of intensity grade or relation to vaccination.
5. Number of Maternal Participants Reporting (S)AEs Leading to Study Withdrawal From Day 1 up to 42 Days Post-delivery [ Time Frame: From Day 1 up to 42 days post-delivery, an average of 2 months ]
   A participant was considered to have withdrawn from the study if no new study procedure had been performed or no new information had been collected for her since the date of withdrawal/last contact. (S)AEs leading to study withdrawal were (S)AEs identified by the investigator to cause participant withdrawal until the resolution of the event. These participant withdrawals were considered different from participant withdrawals for other reasons.
6. Percentage of Maternal Participants Reporting Medically Attended Adverse Events (MAEs) From Day 1 up to 42 Days Post-delivery [ Time Frame: From Day 1 up to 42 days post-delivery, an average of 2 months ]
   An MAE was defined as an unsolicited AE for which the participant received medical attention such as hospitalization, or an emergency room visit, or visit to/by a health care provider.
7. Percentage of Live Births With no Congenital Anomalies, Live Births With Minor Congenital Anomaly(Ies) and Live Births With at Least 1 Major Congenital Anomaly [ Time Frame: From Day 1 up to 42 days post-delivery, an average of 2 months ]
   The percentage of live births with no congenital anomalies, live births with minor congenital anomaly(ies) only and live births with at least 1 major congenital anomaly is reported.
8. Percentage of Maternal Participants Reporting Pregnancy-related Adverse Events of Special Interest (AESIs) From Day 1 up to 42 Days Post-delivery [ Time Frame: From Day 1 up to 42 days post-delivery, an average of 2 months ]
   Pregnancy-related AESIs included preterm labor, provider-initiated preterm birth, premature preterm rupture of membranes, pre-eclampsia, pre-eclampsia with severe features including eclampsia, gestational hypertension and fetal growth restriction.
9. Percentage of Maternal Participants Reporting Worsening of Pre-existing Medical Conditions and/or Obstetric Complications From Day 1 up to 42 Days Post-delivery [ Time Frame: From Day 1 up to 42 days post-delivery, an average of 2 months ]

   Worsening of pre-existing medical condition and/or obstetric complication was considered by the investigator, using clinical judgment and the following criteria:

   • Change in medication and/or medication dose.
   • Medically attended event in relation to pre-existing condition and/or obstetric complication that are outside the routine management of the condition/complication.
   • SAE and/or hospitalization in relation to pre-existing condition and/or obstetric complication.
10. Percentage of Infant Participants Reporting Neonatal/Infant AESIs From Birth up to 42 Days Post-birth [ Time Frame: From birth up to 42 days post-birth, an average of 2 months ]
    Neonatal/infant AESIs included low birth weight (below [<] 2500 grams), very low birth weight (<1500 grams), extremely low birth weight (<1000 grams), preterm birth (<37 weeks of gestational age), small for gestational age (weight below 10th percentile for gestational age), congenital anomalies with internal structural defects and neonatal death in a preterm live birth (gestational age equal to or above [>=] 28 and <37 weeks).
11. Percentage of Infant Participants Reporting Any SAEs From Birth up to 42 Days Post-birth [ Time Frame: From birth up to 42 days post-birth, an average of 2 months ]
    An SAE was 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. Any = occurrence of any SAE regardless of intensity grade or relation to vaccination.
12. Number of Infant Participants Reporting (S)AEs Leading to Study Withdrawal From Birth up to 42 Days Post-birth [ Time Frame: From birth up to 42 days post-birth, an average of 2 months ]
    A participant was considered to have withdrawn from the study if no new study procedure had been performed or no new information had been collected for her since the date of withdrawal/last contact. (S)AEs leading to study withdrawal were (S)AEs identified by the investigator to cause participant withdrawal until the resolution of the event. These participant withdrawals were considered different from participant withdrawals for other reasons.
13. Percentage of Infant Participants Reporting MAEs From Birth up to 42 Days Post-birth [ Time Frame: From birth up to 42 days post-birth, an average of 2 months ]
    An MAE was defined as an unsolicited AE for which the participants received medical attention such as hospitalization, or an emergency room visit, or visit to/by a health care provider.
14. Percentage of Infant Participants Reporting Any SAEs From Birth up to 180 Days Post-birth [ Time Frame: From birth up to 180 days post-birth ]
    An SAE was 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. Any = occurrence of any SAE regardless of intensity grade or relation to vaccination.
15. Number of Infant Participants Reporting (S)AEs Leading to Study Withdrawal From Birth up to 180 Days Post-birth [ Time Frame: From birth up to 180 days post-birth ]
    A participant was considered to have withdrawn from the study if no new study procedure had been performed or no new information had been collected for her since the date of withdrawal/last contact. (S)AEs leading to study withdrawal were (S)AEs identified by the investigator to cause participant withdrawal until the resolution of the event. These participant withdrawals were considered different from participant withdrawals for other reasons.
16. Percentage of Infant Participants Reporting MAEs From Birth up to 180 Days Post-birth [ Time Frame: From birth up to 180 days post-birth ]
    An MAE was defined as an unsolicited AE for which the participants received medical attention such as hospitalization, or an emergency room visit, or visit to/by a health care provider.
17. Percentage of Infant Participants Reporting Any SAEs From Birth up to 365 Days Post-birth [ Time Frame: From birth up to 365 days post-birth ]
    An SAE was 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. Any = occurrence of any SAE regardless of intensity grade or relation to vaccination.
18. Number of Infant Participants Reporting (S)AEs Leading to Study Withdrawal From Birth up to 365 Days Post-birth [ Time Frame: From birth up to 365 days post-birth ]
    A participant was considered to have withdrawn from the study if no new study procedure had been performed or no new information had been collected for her since the date of withdrawal/last contact. (S)AEs leading to study withdrawal were (S)AEs identified by the investigator to cause participant withdrawal until the resolution of the event. These participant withdrawals were considered different from participant withdrawals for other reasons.
19. Percentage of Infant Participants Reporting MAEs From Birth up to 365 Days Post-birth [ Time Frame: From birth up to 365 days post-birth ]
    An MAE was defined as an unsolicited AE for which the participants received medical attention such as hospitalization, or an emergency room visit, or visit to/by a health care provider.
20. RSV MAT Immunoglobulin G (IgG)-Specific Antibody Concentrations for Maternal Participants at Pre-dosing (Day 1) [ Time Frame: At pre-dosing (Day 1) ]
    RSV MAT IgG-specific antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs) in ELISA units per milliliter (ELU/mL).
21. RSV MAT IgG-specific Antibody Concentrations for Maternal Participants at Delivery [ Time Frame: At delivery ]
    RSV MAT IgG-specific antibody concentrations were determined by ELISA and expressed as GMCs in ELU/mL.
22. RSV-A Neutralizing Titers for Maternal Participants at Pre-dosing (Day 1) [ Time Frame: At pre-dosing (Day 1) ]
    RSV-A neutralizing titers were determined by neutralization assay and expressed as geometric mean titers (GMTs).
23. RSV-A Neutralizing Titers for Maternal Participants at Delivery [ Time Frame: At delivery ]
    RSV-A neutralizing titers were determined by neutralization assay and expressed as GMTs.
24. Geometric Mean Ratio (GMR) Between Cord Blood and Maternal RSV MAT IgG-specific Antibody Concentrations [ Time Frame: At delivery (for maternal participants) or within 72 hours after birth (for infant participants) ]
    The placental transfer ratio of IgG-specific antibody concentration was determined from cord blood (or infant blood sample collected within 72 hours after birth [if no cord blood could be obtained]) over that of the blood sample from mother at delivery (if no blood sample was collected during delivery).
25. RSV MAT IgG-specific Antibody Concentrations for Infant Participants at Delivery or Within 72 Hours After Birth [ Time Frame: At delivery or within 72 hours after birth ]
    RSV MAT IgG-specific antibody concentrations were determined by ELISA and expressed as GMCs in ELU/mL. The antibody concentrations were measured on the cord blood sample collected at delivery, or on a blood sample collected from the infant within 72 hours after birth (if no cord blood sample could be obtained).
26. RSV-A Neutralizing Titers for Infant Participants at Delivery or Within 72 Hours After Birth [ Time Frame: At delivery or within 72 hours after birth ]
    RSV-A neutralizing titers were determined by neutralization assay and expressed as GMTs. The titers were measured on the cord blood sample collected at delivery, or on a blood sample collected from the infant within 72 hours after birth (if no cord blood sample could be obtained).

Secondary Outcome Measures :

1. Percentage of Maternal Participants Reporting Any SAEs From Day 1 up to 180 Days Post-delivery [ Time Frame: From Day 1 up to 180 days post-delivery ]
   An SAE was 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 in the offspring of a study participant or resulted in abnormal pregnancy outcomes or in other situations that were considered serious per medical or scientific judgment. Any = occurrence of any SAE regardless of intensity grade or relation to vaccination.
2. Number of Maternal Participants Reporting (S)AEs Leading to Study Withdrawal From Day 1 up to 180 Days Post-delivery [ Time Frame: From Day 1 up to 180 days post-delivery ]
   A participant was considered to have withdrawn from the study if no new study procedure had been performed or no new information had been collected for her since the date of withdrawal/last contact. (S)AEs leading to study withdrawal were (S)AEs identified by the investigator to cause participant withdrawal until the resolution of the event. These participant withdrawals were considered different from participant withdrawals for other reasons.
3. Percentage of Maternal Participants Reporting MAEs From Day 1 up to 180 Days Post-delivery [ Time Frame: From Day 1 up to 180 days post-delivery ]
   An MAE was defined as an unsolicited AE for which the participants received medical attention such as hospitalization, or an emergency room visit, or visit to/by a health care provider.
4. Percentage of Maternal Participants Reporting Worsening of Pre-existing Medical Conditions and/or Obstetric Complications From Day 1 up to 180 Days Post-delivery [ Time Frame: From Day 1 up to 180 days post-delivery ]

   Worsening of pre-existing medical condition and/or obstetric complication was considered by the investigator, using clinical judgement and the following criteria:

   • Change in medication and/or medication dose.
   • Medically attended event in relation to pre-existing condition and/or obstetric complication that are outside the routine management of the condition/complication.
   • SAE and/or hospitalization in relation to pre-existing condition and/or obstetric complication.
5. Number of Maternal Participants Reporting RSV-associated Medically Attended Respiratory Tract Illnesses (MA-RTIs) From Day 1 up to 180 Days Post-delivery [ Time Frame: From Day 1 up to 180 days post-delivery ]
   RSV-associated MA-RTI was defined as a medically attended visit for RTI symptoms and confirmed RSV infection.
6. Percentage of Infant Participants Reporting Medically Assessed, RSV-associated Lower Respiratory Tract Illness (LRTIs) of Any Severity and RSV-associated Severe LRTIs From Birth up to 365 Days Post-birth [ Time Frame: From birth up to 365 days post-birth ]
   An RSV-associated LRTI is 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 meets the case definition of RSV-LRTI AND is additionally characterized by a SpO2 <93%, OR lower chest wall in-drawing, OR inability to feed, OR failure to respond/unconscious.
7. Percentage of Infant Participants Reporting Medically Assessed, RSV-associated Hospitalizations From Birth up to 365 Days Post-birth [ Time Frame: From birth up to 365 days post-birth ]
   RSV-associated hospitalization was defined as a confirmed RSV infection and hospitalized for acute medical condition. Hospitalization was defined as admission for observation or treatment based on the judgment of a health care provider.
8. RSV MAT IgG-specific Antibody Concentrations for Maternal Participants at Day 31 Post-dosing [ Time Frame: At Day 31 post-dosing ]
   RSV MAT IgG-specific antibody concentrations were determined by ELISA and expressed as GMCs in ELU/mL.
9. RSV-A Neutralizing Titers for Maternal Participants at Day 31 Post-dosing [ Time Frame: At Day 31 post-dosing ]
   RSV-A neutralizing titers were determined by neutralization assay and expressed as GMTs.
10. RSV-B Neutralizing Titers for Maternal Participants at Pre-dosing (Day 1), Day 31 Post-dosing and Delivery [ Time Frame: At pre-dosing (Day 1), Day 31 post-dosing and delivery ]
    RSV-B neutralizing titers were determined by neutralization assay and expressed as GMTs.
11. RSV-B Neutralizing Titers for Infant Participants at Delivery or Within 72 Hours After Birth [ Time Frame: At delivery or within 72 hours after birth ]
    RSV-B neutralizing titers were determined by neutralization assay and expressed as GMTs. The titers were measured on the cord blood sample collected at delivery, or on a blood sample collected from the infant within 72 hours after birth (if no cord blood sample could be obtained).
12. RSV MAT IgG-specific Antibody Concentrations for Infant Participants at Day 43 Post-birth [ Time Frame: At Day 43 post-birth ]
    RSV MAT IgG-specific antibody concentrations were determined by ELISA and expressed as GMCs in ELU/mL.
13. RSV MAT IgG-specific Antibody Concentrations for Infant Participants at Day 121 Post-birth [ Time Frame: At Day 121 post-birth ]
    RSV MAT IgG-specific antibody concentrations were determined by ELISA and expressed as GMCs in ELU/mL.
14. RSV MAT IgG-specific Antibody Concentrations for Infant Participants at Day 181 Post-birth [ Time Frame: At Day 181 post-birth ]
    RSV MAT IgG-specific antibody concentrations were determined by ELISA and expressed as GMCs in ELU/mL.
15. RSV-A Neutralizing Titers for Infant Participants at Day 43 Post-birth [ Time Frame: At Day 43 post-birth ]
    RSV-A neutralizing titers were determined by neutralization assay and expressed as GMTs.
16. RSV-A Neutralizing Titers for Infant Participants at Day 121 Post-birth [ Time Frame: At Day 121 post-birth ]
    RSV-A neutralizing titers were determined by neutralization assay and expressed as GMTs.
17. RSV-A Neutralizing Titers for Infant Participants at Day 181 Post-birth [ Time Frame: At Day 181 post-birth ]
    RSV-A neutralizing titers were determined by neutralization assay and expressed as GMTs.
18. RSV-B Neutralizing Titers for Infant Participants at Day 43 Post-birth [ Time Frame: At Day 43 post-birth ]
    RSV-B neutralizing titers were determined by neutralization assay and expressed as GMTs.
19. RSV-B Neutralizing Titers for Infant Participants at Day 121 Post-birth [ Time Frame: At Day 121 post-birth ]
    RSV-B neutralizing titers were determined by neutralization assay and expressed as GMTs.
20. RSV-B Neutralizing Titers for Infant Participants at Day 181 Post-birth [ Time Frame: At Day 181 post-birth ]
    RSV-B neutralizing titers were determined by neutralization assay and expressed as GMTs.

Eligibility Criteria

• Ages Eligible for Study: 15 Years to 49 Years (Child, Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Only pregnant women, 15 to 49 YOA were included in the study.
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

Maternal participants

• Participants who can and will comply with the requirements of the protocol.

• Participants and LARs who give written or witnessed/thumb printed informed consent after the study has been explained according to local regulatory requirements, and before any study specific procedures are performed. The informed consent given at screening should either:

  • include consent for both the maternal participant's participation* and participation of the infant after the infant's birth, or
  • include consent for the maternal participant's participation* and expressed willingness to consider permitting the infant to take part after the infant's birth (if local regulations/guidelines require parent(s) to provide an additional informed consent after the infant's birth).
  • both mother and father should consent if local regulations / guidelines require it.
• Pre-pregnancy Body Mass Index (based on participant's report) 18.5 to 39.9 kg/m^2, inclusive.
• Healthy adolescent pregnant women, 15 to 17 YOA, inclusive, at the time of study intervention administration.

OR

• Pregnant women, 18 to 49 YOA, inclusive, at the time of study intervention administration with:

  • HIV infection AND/OR
  • Obstetric complications or risk factors during the current pregnancy, where the expectant management of the pregnancy is possible and without evidence of non-reassuring fetal status (only cases for which fetal heart rate can be ascertained) as follows:
  • Gestational diabetes, well-controlled on medications (with or without diet or exercise)
  • Gestational hypertension, well-controlled on diet or medications below 160/110 mmHg.
  • Pre-eclampsia without severe features (i.e. eclampsia, severe hypertension [>160/110 mmHg], organ dysfunction, unstable or complicated by [HELLP] syndrome).
  • Fetal Growth Restriction in singleton pregnancies, with normal umbilical artery Doppler and estimated fetal weight 3 to 10th percentile for gestational age.
  • History of threatened preterm labor in the current pregnancy, with no cervical dilation greater than 2 cm or effacement exceeding 50%, and/or no progressive change in cervical dilation or effacement detected by serial examinations, when maternal participant is asymptomatic
  • Uncomplicated twin gestation.

• Pregnant females at 24^0/7 to 36^0/7 weeks of gestation at the time of study intervention administration (Day 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).
  • First or second 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.

The level of diagnostic certainty of the gestational age should be established by using the Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) gestation age assessment tool

• Participants who are willing to provide cord blood.
• Willing to have their offspring followed-up after delivery for a period of 12 months.
• Participants who do not plan to give their offspring for adoption or place the child in care.

Note that women whose pregnancies resulted from Assisted Reproductive Technologies may be enrolled if they meet all inclusion criteria and none of the exclusion criteria.

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 infant study specific procedure. To comply with RTI surveillance and other protocol required procedures that begin immediately after birth: if written consent cannot be provided by the parent(s)/LAR(s) readily post-birth, verbal consent - if permitted per local regulation -- may be sought from the parent(s) / LAR(s) instead. Verbal consent should be documented in the source data by the investigator or delegate. The parent(s) / LAR(s) will provide additional, written informed consent by (or before) Visit 2-NB.

Exclusion Criteria:

Maternal participants Medical conditions

• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention.
• Hypersensitivity to latex.
• Any pre-existing medical conditions or obstetric complications in the current pregnancy that, are poorly controlled and/or with clinical evidence of a non-reassuring fetal status and/or are likely to result in delivery within 7 days after study intervention administration and/or when the timing of planned delivery is within 7 days after study intervention administration and/or acute conditions requiring immediate medical attention for maternal stabilization and/or treatment.
• A multiple pregnancy with 3 or more fetuses.
• Complicated twin gestation.
• Placenta Accreta Spectrum, including placenta increta, percreta, and accreta.
• Fetal structural defects or genetic abnormalities that affect (or are likely to affect) fetal health or survival during the first year of life.
• Known or suspected impairment of the immune system or immunodeficiency syndrome other than HIV.
• Lymphoproliferative disorder or malignancy within 5 years before study dose administration.
• Any illness of the mother or conditions of the fetus that, may substantially interfere with the maternal participant's ability to comply with study procedures, or could increase the risks to the mother or the fetus, or could preclude the evaluation of the participant's data.
• Any other clinical condition that, might pose additional risk to the participant due to participation in the study, as determined by medical history, physical examination or laboratory screening tests.
• Women with any diagnosis, condition, treatment, or other factor that, has the potential to affect or confound assessments of immunogenicity or safety
• Any conditions which, in the investigator's opinion, would increase the risks of study participation to the unborn infant.

Prior/Concomitant therapy

• Prior receipt of an RSV maternal vaccine.

• Use of any investigational or non-registered product other than the study intervention(s) during the period beginning:

  • For a drug, vaccine or medical device: 29 days before the dose of study intervention(s) (Day -28 to Day 1), or their planned use during the study period.
  • For immunoglobulins: 90 days before the dose of study intervention(s), or their planned use during the study period.

The exception to this is investigational products administered in the setting of a pandemic. Administration in this case should respect the same period outlined above prior to study intervention administration, but may be allowed following delivery.

• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 29 days before the study Day 1 and ending at delivery, with the exception of seasonal influenza vaccines, tetanus vaccines, dTpa/Tdap - alone vaccines, dTpa/Tdap vaccines that also contain other antigens and Hepatitis B vaccines, all of which may be administered according to standard of care ≥ 15 days before or after study intervention (Day 1).
• Receipt of blood or plasma products or immunoglobulin, from 90 days before study intervention administration, or planned receipt through delivery, with the exception of Rho(D) immunoglobulin, which can be given at any time. In that sense, COVID-19 vaccines may be allowed, when administered ≥ 15 days before or after study vaccination.
• Administration of immune-modifying therapy within 6 months before study intervention administration, or planned administration through delivery, except if it is part of management of HIV infection.

Prior/Concurrent clinical study experience

• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention.

Other exclusions

• Alcoholism or substance use disorder within the past 24 months based on the presence of 2 or more of the following abuse criteria: hazardous use, social/interpersonal problems related to use, neglect of major roles to use, withdrawal, tolerance, use of larger amounts or longer, repeated attempts to quit or control use, much time spent using, physical or psychological problems related to use, activities given up to use, craving.
• A local condition that precludes injection of the study vaccine/product or precludes assessment of local (administration site) reactogenicity.
• Consanguinity of maternal participant and her partner.
• Any study personnel or their immediate dependents, family, or household members.

Infant participants

• Concurrently participating in another clinical trial, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product.
• Any condition which, would increase the risks of study participation to the infant.
• Child in care.

Contacts and Locations

Locations

United States, Alabama

GSK Investigational Site

Birmingham, Alabama, United States, 35205

GSK Investigational Site

Dothan, Alabama, United States, 36305

GSK Investigational Site

Mobile, Alabama, United States, 36608

United States, Arizona

GSK Investigational Site

Phoenix, Arizona, United States, 85015

United States, Louisiana

GSK Investigational Site

Covington, Louisiana, United States, 70433

GSK Investigational Site

Lafayette, Louisiana, United States, 70508

GSK Investigational Site

Slidell, Louisiana, United States, 70458

United States, Montana

GSK Investigational Site

Missoula, Montana, United States, 59804

United States, Texas

GSK Investigational Site

Arlington, Texas, United States, 76012

GSK Investigational Site

Austin, Texas, United States, 78705

GSK Investigational Site

Fort Worth, Texas, United States, 76104

GSK Investigational Site

Houston, Texas, United States, 77008

GSK Investigational Site

League City, Texas, United States, 77573

GSK Investigational Site

Plano, Texas, United States, 75093

GSK Investigational Site

Weatherford, Texas, United States, 76086

Brazil

GSK Investigational Site

Caxias do Sul, Rio Grande Do Sul, Brazil, 95070-560

GSK Investigational Site

Santa Maria, Rio Grande Do Sul, Brazil, 97105-900

GSK Investigational Site

Ribeirao Preto, São Paulo, Brazil, 14048-900

Canada, Nova Scotia

GSK Investigational Site

Halifax, Nova Scotia, Canada, B3K 6R8

Canada, Ontario

GSK Investigational Site

Montreal, Ontario, Canada, H3T 1C5

Canada

GSK Investigational Site

Québec, Canada, G1V 4G2

Finland

GSK Investigational Site

Helsinki, Finland, 00290

India

GSK Investigational Site

Bhubaneshwar, Odisha, India, 751019

GSK Investigational Site

Mysuru, India, 570015

Italy

GSK Investigational Site

Messina, Sicilia, Italy, 98124

GSK Investigational Site

Prato, Toscana, Italy, 59100

GSK Investigational Site

Perugia, Umbria, Italy, 06129

Panama

GSK Investigational Site

Ciudad de Panama, Panama, 7099

GSK Investigational Site

Panama, Panama, 0801

South Africa

GSK Investigational Site

Soweto, Gauteng, South Africa, 2013

Spain

GSK Investigational Site

Malaga, Andalucia, Spain, 29004

GSK Investigational Site

Boadilla Del Monte (Madrid), Spain, 28660

GSK Investigational Site

Madrid, Spain, 28041

GSK Investigational Site

Madrid, Spain, 28046

GSK Investigational Site

Majadahonda (Madrid), Spain, 28222

GSK Investigational Site

Torrejón Ardoz, Spain, 28850

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:

Study Protocol  [PDF] March 16, 2022

Statistical Analysis Plan  [PDF] June 1, 2022

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT04980391
• Other Study ID Numbers: 214725; 2021-000994-96 ( EudraCT Number )
• First Posted: July 28, 2021
• Results First Posted: February 6, 2024
• Last Update Posted: February 6, 2024
• Last Verified: January 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by GlaxoSmithKline:

Respiratory Syncytial Virus Maternal vaccine; Safety; Reactogenicity; Immune response; High risk pregnant women; Teenage girls

Additional relevant MeSH terms:

Respiratory Syncytial Virus Infections; Virus Diseases; Infections; Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections