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

NCT04980391 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: 2147252021-000994-96
• Study Type: interventional
• Target: 384
• Locations: 9 countries
• Sites: 35

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.

Conditions

Respiratory Syncytial Virus Infections

Keywords

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

Outcome Measures

Primary Outcomes (26)

• Percentage of Maternal Participants Reporting Any Solicited Administration Site Events

  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.

  From Day 1 to Day 7 included

• Percentage of Maternal Participants Reporting Any Solicited Systemic Events

  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.

  From Day 1 to Day 7 included

• Percentage of Maternal Participants Reporting Any Unsolicited Adverse Events (AEs)

  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.

  From Day 1 to Day 30 included

• Percentage of Maternal Participants Reporting Any Serious Adverse Events (SAEs) From Day 1 up to 42 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.

  From Day 1 up to 42 days post-delivery, an average of 2 months

• Number of Maternal Participants Reporting (S)AEs Leading to Study Withdrawal From Day 1 up to 42 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.

  From Day 1 up to 42 days post-delivery, an average of 2 months

• Percentage of Maternal Participants Reporting Medically Attended Adverse Events (MAEs) From Day 1 up to 42 Days Post-delivery

  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.

  From Day 1 up to 42 days post-delivery, an average of 2 months

• 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

  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.

  From Day 1 up to 42 days post-delivery, an average of 2 months

• Percentage of Maternal Participants Reporting Pregnancy-related Adverse Events of Special Interest (AESIs) From Day 1 up to 42 Days Post-delivery

  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.

  From Day 1 up to 42 days post-delivery, an average of 2 months

• Percentage of Maternal Participants Reporting Worsening of Pre-existing Medical Conditions and/or Obstetric Complications From Day 1 up to 42 Days Post-delivery

  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.

  From Day 1 up to 42 days post-delivery, an average of 2 months

• Percentage of Infant Participants Reporting Neonatal/Infant AESIs From Birth up to 42 Days Post-birth

  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).

  From birth up to 42 days post-birth, an average of 2 months

• Percentage of Infant Participants Reporting Any SAEs From Birth up to 42 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.

  From birth up to 42 days post-birth, an average of 2 months

• Number of Infant Participants Reporting (S)AEs Leading to Study Withdrawal From Birth up to 42 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.

  From birth up to 42 days post-birth, an average of 2 months

• Percentage of Infant Participants Reporting MAEs From Birth up to 42 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.

  From birth up to 42 days post-birth, an average of 2 months

• Percentage of Infant Participants Reporting Any SAEs 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.

  From birth up to 180 days post-birth

• Number of Infant Participants Reporting (S)AEs Leading to Study Withdrawal 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.

  From birth up to 180 days post-birth

• Percentage of Infant Participants Reporting MAEs 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.

  From birth up to 180 days post-birth

• Percentage of Infant Participants Reporting Any SAEs 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.

  From birth up to 365 days post-birth

• Number of Infant Participants Reporting (S)AEs Leading to Study Withdrawal 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.

  From birth up to 365 days post-birth

• Percentage of Infant Participants Reporting MAEs 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.

  From birth up to 365 days post-birth

• RSV MAT Immunoglobulin G (IgG)-Specific Antibody Concentrations for Maternal Participants 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).

  At pre-dosing (Day 1)

• RSV MAT IgG-specific Antibody Concentrations for Maternal Participants at Delivery

  RSV MAT IgG-specific antibody concentrations were determined by ELISA and expressed as GMCs in ELU/mL.

  At delivery

• RSV-A Neutralizing Titers for Maternal Participants at Pre-dosing (Day 1)

  RSV-A neutralizing titers were determined by neutralization assay and expressed as geometric mean titers (GMTs).

  At pre-dosing (Day 1)

• RSV-A Neutralizing Titers for Maternal Participants at Delivery

  RSV-A neutralizing titers were determined by neutralization assay and expressed as GMTs.

  At delivery

• Geometric Mean Ratio (GMR) Between Cord Blood and Maternal RSV MAT IgG-specific Antibody Concentrations

  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).

  At delivery (for maternal participants) or within 72 hours after birth (for infant participants)

• RSV MAT IgG-specific Antibody Concentrations for Infant Participants 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).

  At delivery or within 72 hours after birth

• RSV-A Neutralizing Titers for Infant Participants 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).

  At delivery or within 72 hours after birth

Secondary Outcomes (20)

• Percentage of Maternal Participants Reporting Any SAEs From Day 1 up to 180 Days Post-delivery

  From Day 1 up to 180 days post-delivery

• Number of Maternal Participants Reporting (S)AEs Leading to Study Withdrawal From Day 1 up to 180 Days Post-delivery

  From Day 1 up to 180 days post-delivery

• Percentage of Maternal Participants Reporting MAEs From Day 1 up to 180 Days Post-delivery

  From Day 1 up to 180 days post-delivery

• Percentage of Maternal Participants Reporting Worsening of Pre-existing Medical Conditions and/or Obstetric Complications From Day 1 up to 180 Days Post-delivery

  From Day 1 up to 180 days post-delivery

• Number of Maternal Participants Reporting RSV-associated Medically Attended Respiratory Tract Illnesses (MA-RTIs) From Day 1 up to 180 Days Post-delivery

  From Day 1 up to 180 days post-delivery

Study Arms (4)

RSV_MAT Group

EXPERIMENTAL

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

Control Group

PLACEBO COMPARATOR

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

RSV_MAT Group-Infant

NO INTERVENTION

This group consisted of infants born to mothers (from RSV\_MAT Group-Mother) who received a single dose of RSV MAT vaccine during pregnancy.

Control Group-Infant

NO INTERVENTION

This group consisted of infants born to mothers (from Control Group-Mother) who received a single dose of placebo during pregnancy.

Interventions

RSV MAT BIOLOGICAL

Single dose of the RSV MAT vaccine reconstituted with NaCl solution, administered intramuscularly in the non-dominant arm, at Day 1.

RSV_MAT Group

Placebo DRUG

Single dose of placebo, administered intramuscularly in the non-dominant arm, at Day 1.

Control Group

Eligibility Criteria

• Age: 15 Years - 49 Years
• Gender Eligibility Details: Only pregnant women, 15 to 49 YOA were included in the study.
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (35)

GSK Investigational Site

Birmingham, Alabama, 35205, United States

Location

GSK Investigational Site

Dothan, Alabama, 36305, United States

Location

GSK Investigational Site

Mobile, Alabama, 36608, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85015, United States

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GSK Investigational Site

Covington, Louisiana, 70433, United States

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GSK Investigational Site

Lafayette, Louisiana, 70508, United States

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GSK Investigational Site

Slidell, Louisiana, 70458, United States

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GSK Investigational Site

Missoula, Montana, 59804, United States

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GSK Investigational Site

Arlington, Texas, 76012, United States

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GSK Investigational Site

Austin, Texas, 78705, United States

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GSK Investigational Site

Fort Worth, Texas, 76104, United States

Location

GSK Investigational Site

Grapevine, Texas, 76051, United States

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GSK Investigational Site

Houston, Texas, 77008, United States

Location

GSK Investigational Site

League City, Texas, 77573, United States

Location

GSK Investigational Site

Plano, Texas, 75093, United States

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GSK Investigational Site

Weatherford, Texas, 76086, United States

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GSK Investigational Site

Caxias do Sul, 95070-560, Brazil

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GSK Investigational Site

RibeirAo PretoSP, 14048-900, Brazil

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GSK Investigational Site

Santa Maria, 97105-900, Brazil

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GSK Investigational Site

Halifax, Nova Scotia, B3K 6R8, Canada

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GSK Investigational Site

Montreal, Quebec, H3T 1C5, Canada

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GSK Investigational Site

Helsinki, 00290, Finland

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GSK Investigational Site

Bhubaneswar, 751019, India

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GSK Investigational Site

Mysuru, 570015, India

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GSK Investigational Site

Messina, 98124, Italy

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GSK Investigational Site

Perugia, 06129, Italy

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GSK Investigational Site

Prato, 59100, Italy

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GSK Investigational Site

Panama City, 0801, Panama

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GSK Investigational Site

Soweto Gauteng, 2013, South Africa

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GSK Investigational Site

Boadilla Del Monte Madrid, 28660, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

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GSK Investigational Site

Madrid, 28222, Spain

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GSK Investigational Site

Málaga, 29004, Spain

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GSK Investigational Site

TorrejOn Ardoz Madrid, 28850, Spain

Location

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The study was unblinded to ensure the participant's safety.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2021
• First Posted: July 28, 2021
• Study Start: August 3, 2021
• Primary Completion: May 30, 2023
• Study Completion: May 30, 2023
• Last Updated: April 20, 2025
• Results First Posted: February 6, 2024

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

PA (1); FI (1); IN (2); US (16); BR (3); ES (6); ZA (1); IT (3); CA (2)