Study of Safety, Reactogenicity and Immunogenicity of GlaxoSmithKline's (GSK)Respiratory Syncytial Virus (RSV)Maternal Unadjuvanted Vaccine in Healthy Pregnant Women (Aged 18 to 40 Years) and Their Infants

NCT04126213 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2095442019-001991-12
• Study Type: interventional
• Target: 534
• Locations: 9 countries
• Sites: 32

Brief Summary

The purpose of this study was to evaluate the safety and immune response to a single intramuscular (IM) dose of GSK Biologicals' investigational RSV maternal vaccine (RSVPreF3) in healthy pregnant women 18-40 years of age and in infants born to vaccinated mothers.

Conditions

Respiratory Syncytial Virus Infections

Outcome Measures

Primary Outcomes (19)

• Percentage of Maternal Subjects With Any Solicited Administration Site Events

  Assessed solicited administration site events were pain, erythema and swelling. Any = occurrence of the symptom regardless of intensity grade. Any erythema and swelling symptom = symptom reported with a surface diameter greater than 0 millimeters.

  During the 7-day follow-up period after vaccination (i.e. day of vaccination and 6 subsequent days)

• Percentage of Maternal Subjects With Any Solicited Systemic Events

  Assessed solicited systemic events were fatigue, headache, nausea, vomiting, diarrhea, abdominal pain and fever \[temperature equal to or above (≥) 38 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade or relation to study intervention.

  During the 7-day follow-up period after vaccination (i.e. day of vaccination and 6 subsequent days)

• Number of Maternal Subjects With Any Haematological Laboratory Abnormalities at Day 8 by Baseline Ranges

  Hematological parameters assessed were Eosinophils (EOS), Erythrocytes (ERY), Hematocrit (HEM), Lymphocytes (LYMP), Mean Corpuscular Volume (MCV), Neutrophils (NEU), Platelets (PLA), and White Blood Cells (WBC) count. The increase and/or decrease of these parameters were evaluated at Day 8. Abnormal laboratory values refer to range indicator at Day 8 (D8) categorized as Missing, Below, Within and Above normal values and compared to the baseline (B) range indicator of the same parameter, at Screening (up to 15 days before vaccination) i.e. Missing, Below, Within and Above. E.g. 'WBC decrease Below (B) - Within (D8)' = WBC decrease in subjects with below normal values at baseline and within normal values at Day 8.

  At Day 8

• Number of Maternal Subjects With Any Biochemical Laboratory Abnormalities at Day 8 by Baseline Ranges

  Biochemical parameters assessed were Alanine Amino-Transferase (ALT), Aspartate Amino-Transferase (AST), Creatinine (CRE) and Urea nitrogen (URN). The increase was evaluated only for AST and ALT parameters at Day 8. Abnormal laboratory values refer to range indicator at Day 8 (D8) categorized as Missing, Below, Within and Above normal values and compared to the baseline (B) range indicator of the same parameter, at Screening (up to 15 days before vaccination) i.e. Missing, Below, Within and Above. E.g. 'AST increase Below (B) - Within (D8)' = AST increase in subjects with below normal values at baseline and within normal values at Day 8.

  At Day 8

• Percentage of Maternal Subjects With Any Unsolicited Adverse Events (AEs)

  An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Unsolicited AE is any AE reported in addition to those solicited during the clinical study and that was spontaneously communicated by a maternal subject. Also, any solicited symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited AE. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

  During 30-day follow-up period after vaccination (i.e. the day of vaccination and 29 subsequent days)

• Percentage of Maternal Subjects With Any Serious Adverse Events (SAEs)

  SAEs assessed included any untoward medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study subject or abnormal pregnancy outcomes (spontaneous abortion, foetal death, stillbirth, congenital anomalies, ectopic pregnancy), other situations (medical events that might jeopardize the participant or required medical/surgical intervention to prevent one of the other SAEs listed above: e.g. invasive/malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization). Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination.

  From Day 1 to Day 43 post-delivery

• Percentage of Maternal Subjects With AEs Leading to Study Withdrawal

  An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs leading to study withdrawal = AEs identified by investigators to cause subject(s) withdrawal until the resolution of the event. These subject withdrawals were considered different from subject withdrawals for other reasons.

  From Day 1 to Day 43 post-delivery

• Percentage of Maternal Subjects With Any Medically Attended AEs (MAE)

  MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Also, for instances where, due to the special circumstances, the subject could not seek medical advice for symptoms/an illness by visiting a medical facility or arranging for a home visit, the subject sought this advice instead via telephone, SMS, email, videotelephony or telemedicine, or other means. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination.

  From Day 1 to Day 43 post-delivery

• Percentage of Maternal Subjects With Pregnancy Outcomes

  Pregnancy outcomes were: live birth with no congenital anomalies, live birth with congenital anomalies, Fetal death/still birth with no Congenital Anomalies (CA) - Antepartum and Unknown (Subjects withdrew from the study before delivery and pregnancy outcome information was not available for them).

  From Day 1 to Day 43 post-delivery

• Percentage of Maternal Subjects With Pregnancy-related Adverse Events of Special Interest (AESIs)

  Pregnancy-related AESIs were: Non-Reassuring Fetal Status, Hypertensive Disorders of Pregnancy (HDP), Oligohydramnios, Pathways to Preterm Birth (PPB), Chorioamnionitis, Fetal Growth Restriction, Gestational Liver Disease (GLD), Postpartum Haemorrhage and Gestational Diabetes Mellitus.

  From Day 1 to Day 43 post-delivery

• Percentage of Infant Subjects With Neonatal AESIs

  Neonatal AESIs, reported up to 6 weeks after birth were: Respiratory Distress In The Neonate, Macrosomia, Low Birth Weight, Small For Gestational Age, Preterm Birth, Large For Gestational Age, Neonatal Invasive Blood Stream Infections (NIBSI) and Congenital Anomalies (CA).

  From birth to Day 43 post-birth

• Percentage of Infant Subjects With Any SAEs

  SAEs assessed included any untoward medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity or is a congenital anomaly/birth defect, other situations (medical events that might jeopardize the participant or required medical/surgical intervention to prevent one of the other SAEs listed above: e.g. invasive/malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization). Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination.

  From birth to Day 43 post-birth

• Percentage of Infant Subjects With AEs Leading to Study Withdrawal

  An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs leading to study withdrawal = AEs identified by investigators to cause subject(s) withdrawal until the resolution of the event. These subject withdrawals were considered different from subject withdrawals for other reasons.

  From birth to Day 43 post-birth

• Percentage of Infant Subjects With Any MAEs

  MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Also, for instances where, due to the special circumstances, the subject could not seek medical advice for symptoms/an illness by visiting a medical facility or arranging for a home visit, the subject sought this advice instead via telephone, SMS, email, videotelephony or telemedicine, or other means. Any = occurrence of the symptom regardless of intensity grade.

  From birth to Day 43 post-birth

• RSV MAT Immunoglobulin G (IgG)-Specific Antibody Concentrations in Terms of Geometric Mean Concentrations (GMCs) in Maternal Subjects

  Serological assays for the determination of IgG antibodies against RSV MAT were performed by Enzyme-linked immunosorbent assay (ELISA). The corresponding antibody concentrations were expressed in ELISA units per milliliter (EU/mL) and were measured on blood samples collected from vaccinated maternal subjects.

  At Day 1 (before vaccination), Day 31 and at delivery

• RSV-A Neutralizing Antibody Geometric Mean Titers (GMTs) in Maternal Subjects

  Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. The corresponding antibody titers were expressed in Estimated Dilution 60 (ED60) and were measured on blood samples collected from vaccinated maternal subjects.

  At Day 1 (before vaccination), Day 31 and at delivery

• RSV MAT IgG Antibody GMCs in Infants Born to Maternal Subjects

  Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. The corresponding antibody concentrations were expressed in EU/mL. The antibodies were measured on the cord blood sample collected at delivery, or on a blood sample collected from the infant within 3 days after birth (if no cord blood sample could be obtained).

  At delivery or within 3 days after birth

• RSV-A Neutralizing Antibody GMTs in Infants Born to Maternal Subjects

  Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. The corresponding antibody titers were presented as GMTs, expressed in ED60. The antibodies were measured on the cord blood sample collected at delivery, or on a blood sample collected from the infant within 3 days after birth (if no cord blood sample could be obtained).

  At delivery or within 3 days after birth

• Geometric Mean Ratio 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 blood sample collected within 3 days after birth from infants if cord blood was not collected) over that of the blood sample from mother at delivery if blood sample was not collected during delivery). Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA.

  At delivery (for maternal subjects) or within 3 days after birth (for infants)

Secondary Outcomes (27)

• Percentage of Maternal Subjects With Any SAE From Day 1 to Day 181 Post Delivery

  From Day 1 to Day 181 post-delivery

• Percentage of Maternal Subjects With Any MAE From Day 1 to Day 181 Post Delivery

  From Day 1 to Day 181 post-delivery

• Percentage of Maternal Subjects With AE Leading to Study Withdrawal From Day 1 to Day 181 Post Delivery

  From Day 1 to Day 181 post-delivery

• Percentage of Infant Subjects With Any SAE From Birth to Day 181 Post-birth

  From birth to Day 181 post-birth

• Percentage of Infant Subjects With AE Leading to Study Withdrawal From Birth to Day 181 Post-birth

  From birth to Day 181 post-birth

Study Arms (6)

RSV MAT 60 Group-Mother

EXPERIMENTAL

Maternal subjects randomized to RSV MAT 60 Group received a single dose of RSV MAT (60 µg) vaccine at Day 1, and were followed up until the study end.

Biological: RSV MAT 60 µg

RSV MAT 120 Group-Mother

EXPERIMENTAL

Maternal subjects randomized to RSV MAT 120 group received a single dose of RSV MAT (120 µg) vaccine at Day 1, and were followed up until the study end.

Biological: RSV MAT 120 µg

Control Group-Mother

PLACEBO COMPARATOR

Maternal subjects randomized to the Control Group received a single dose of Placebo at Day 1, and were followed up until the study end.

Drug: Placebo

RSV MAT 60 Group-Infant

NO INTERVENTION

This group consisted of infants born to mothers (from RSV MAT 60 Group-Mother) who received a single dose of RSV MAT (60 µg) vaccine during pregnancy.

RSV MAT 120 Group-Infant

NO INTERVENTION

This group consisted of infants born to mothers (from RSV MAT 120 Group-Mother) who received a single dose of RSV MAT (120 µg) 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 60 µg BIOLOGICAL

One single dose of RSV MAT 60 µg vaccine administered intramuscularly in the deltoid region of the non-dominant arm on Day 1.

RSV MAT 60 Group-Mother

RSV MAT 120 µg BIOLOGICAL

One single dose of RSV MAT 120 µg vaccine administered intramuscularly in the deltoid region of the non-dominant arm on Day 1.

RSV MAT 120 Group-Mother

Placebo DRUG

One single dose of placebo (NaCl solution) administered intramuscularly in the deltoid region of the non-dominant arm on Day 1.

Control Group-Mother

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Maternal subjects
• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Subjects 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 (consistent with local regulations / guidelines) either:
• include consent for both the maternal subject's participation and participation of the infant after the infant's birth, or
• include consent for the maternal subject's participation and expressed willingness to consider permitting the infant to take part after the infant's birth.
• Both mother and father should consent if local regulations/guidelines require it.
• Age 18 to 40 years, inclusive, when informed consent is given.
• Pre-pregnancy BMI 18.5 to 34.9, inclusive
• Healthy as established by medical history and clinical examination before entering into the study.
• At 28\^0/7 to 33\^6/7 weeks of gestation at the time of study vaccination (Visit 1), as established by last menstrual period (LMP) date corroborated by first or second trimester ultrasound examination (U/S).
• \* If LMP and U/S do not correlate, default to U/S gestational age assessment. The level of diagnostic certainty of the gestational age should be established by using the Global Alignment of Immunisation safety Assessment in pregnancy gestation age assessment tool
• Subject satisfying screening requirements
• Singleton pregnancy
• HIV negative, as assessed by local standard of care serologic tests conducted during the current pregnancy and before enrolment (Visit 1).
• No fetal genetic abnormalities.

You may not qualify if:

• Infant subjects
• Live-born from the study pregnancy.
• 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 legally authorized representative, as applicable by local law, before performing any study specific procedure.
• Maternal subjects
• Medical conditions
• History of allergic disease or reactions likely to be exacerbated by any component of the RSV vaccine
• Hypersensitivity to latex
• Significant complications in the current pregnancy such as:
• Gestational hypertension at ≥20 weeks of gestation in the absence of proteinuria in a woman with a previously normal blood pressure
• Gestational diabetes which is not controlled by diet and exercise
• Pre-eclampsia
• Eclampsia during current pregnancy
• Intrauterine growth restriction
• Placenta previa
• Placental abruption, placenta accreta/percreta/increta, chorioamnionitis or any abnormalities that in the opinion of Investigator can impair the maternal-fetal circulation

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (32)

GSK Investigational Site

Phoenix, Arizona, 85015, United States

Location

GSK Investigational Site

Huntington Park, California, 90255, United States

Location

GSK Investigational Site

Los Angeles, California, 90057, United States

Location

GSK Investigational Site

Nampa, Idaho, 83687, United States

Location

GSK Investigational Site

Metairie, Louisiana, 70006, United States

Location

GSK Investigational Site

Gulfport, Mississippi, 39503, United States

Location

GSK Investigational Site

St Louis, Missouri, 63141, United States

Location

GSK Investigational Site

Albuquerque, New Mexico, 87102, United States

Location

GSK Investigational Site

Johnson City, New York, 13790, United States

Location

GSK Investigational Site

Englewood, Ohio, 45322, United States

Location

GSK Investigational Site

Beaumont, Texas, 77702, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76104, United States

Location

GSK Investigational Site

Plano, Texas, 75093, United States

Location

GSK Investigational Site

South Brisbane, Queensland, 4101, Australia

Location

GSK Investigational Site

Melbourne, Victoria, 3168, Australia

Location

GSK Investigational Site

Halifax, Nova Scotia, B3K 6R8, Canada

Location

GSK Investigational Site

Québec, G1V 4G2, Canada

Location

GSK Investigational Site

Helsinki, 00290, Finland

Location

GSK Investigational Site

Clermont-Ferrand, 63100, France

Location

GSK Investigational Site

Saint-Etienne, 42055, France

Location

GSK Investigational Site

Auckland, 1010, New Zealand

Location

GSK Investigational Site

Wellington, 6021, New Zealand

Location

GSK Investigational Site

Panama City, 0801, Panama

Location

GSK Investigational Site

Panama City, 32401, Panama

Location

GSK Investigational Site

Soweto, Gauteng, 2013, South Africa

Location

GSK Investigational Site

Málaga, Andalusia, 29004, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Burgos, 09006, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Majadahonda (Madrid), 28222, Spain

Location

GSK Investigational Site

Marbella, 29600, Spain

Location

Related Publications (1)

• Bebia Z, Reyes O, Jeanfreau R, Kantele A, De Leon RG, Sanchez MG, Banooni P, Gardener GJ, Rasero JLB, Pardilla MBE, Langley JM, Di Leo CM, Botelho-Nevers E, Buttery J, Laurichesse H, Madhi SA, Garcia AM, Stanley T, Barjat T, Griffith R, Castrejon-Alba MM, de Heusch M, Dieussaert I, Hercor M, Lese P, Qian H, Tullio AN, Henry O. Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus Vaccine (RSVPreF3) in Mothers and Their Infants: A Phase 2 Randomized Trial. J Infect Dis. 2023 Aug 11;228(3):299-310. doi: 10.1093/infdis/jiad024.

  PMID: 36722147 DERIVED

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 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Data was collected in an observer-blind manner. The laboratory in charge of the sample testing was blinded to the intervention assignment, codes were used to link the subject and study (without any link to the intervention attributed to the subject) to each sample. Investigators remained blinded to each subject's assigned study intervention until the second analysis. After the second analysis, the study was not considered observer blind as the investigator brochure was updated to include safety information presented by treatment group. This led to inadvertent unblinding of investigators and site staff to some subjects' treatment assignments. The subjects themselves remained blinded throughout their participation in the study.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2019
• First Posted: October 15, 2019
• Study Start: November 5, 2019
• Primary Completion: July 23, 2020
• Study Completion: May 14, 2021
• Last Updated: December 13, 2021
• Results First Posted: December 13, 2021

Record last verified: 2021-11

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

US (13); FR (2); FI (1); CA (2); AU (2); ES (7); PA (2); ZA (1); NZ (2)