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

NCT ID: NCT04126213

Last Updated: 2021-12-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 534 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-05
• Study Completion Date: 2021-05-14

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

RSV MAT 60 Group-Mother

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.

Group Type: EXPERIMENTAL

RSV MAT 60 µg

Intervention Type: 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 120 Group-Mother

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.

Group Type: EXPERIMENTAL

RSV MAT 120 µg

Intervention Type: BIOLOGICAL

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

Control Group-Mother

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

RSV MAT 60 Group-Infant

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

RSV MAT 120 Group-Infant

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Control Group-Infant

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

RSV MAT 60 µg

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

Intervention Type: BIOLOGICAL

RSV MAT 120 µg

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

Intervention Type: BIOLOGICAL

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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.
• No significant congenital malformations, as assessed by level 2 ultrasound (also known as a fetal anomaly ultrasound scan or fetal morphology assessment) conducted after 18 weeks of gestation
• Willing to provide cord blood
• Willing to have the infant followed-up after delivery for a period of 12 months

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.

Exclusion Criteria

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
• Polyhydramnios
• Oligohydramnios
• Cervical suture in place
• Preterm labour or history of preterm labour in the current pregnancy
• Ongoing medical intervention to prevent preterm delivery or medical treatment for suspected preterm delivery
• Cholestasis
• Other pregnancy-related complications that in the Investigator's judgement would preclude participation of the subjects in an investigational vaccine trial or might pose risk to the subject due to participation in the study
• Significant structural abnormalities of the uterus or cervix
• History of prior stillbirth or neonatal death
• History of preterm birth
• History of ≥2 spontaneous abortions
• Known or suspected HBV or HCV infection, based on medical history and clinical presentation
• Known or suspected infection during the current pregnancy with Toxoplasma, Parvovirus B19, Syphilis, Zika, Rubella, Varicella, CMV or primary genital Herpes Simplex, based on medical history and clinical presentation
• Active infection with tuberculosis, based on medical history and clinical presentation
• Known or suspected impairment of the immune system or autoimmune disorder (based on medical history and physical examination; no laboratory testing required)
• Lymphoproliferative disorder or malignancy within 5 years before vaccination (excluding effectively treated non-melanoma skin cancer)
• Any clinically significant grade 1 hematological and/or biochemical laboratory abnormalities identified at screening, which are clinically significant for pregnant women in the second and third trimester
• Grade ≥ 2 hematological and/or biochemical laboratory abnormalities identified at screening being clinically significant for pregnant women in the second and third trimester
• Acute or chronic clinically significant conditions, that might pose additional risk to the subject due to participation in the study
• Any conditions that, may interfere with subject's ability to comply with study procedures or receipt of prenatal care
• Any condition which, would increase the risks of study participation to the unborn infant

Prior/Concomitant therapy

• Prior receipt of a COVID-19 vaccine.
• Prior receipt of an RSV vaccine
• Use of any investigational or non-registered product other than the study vaccine(s)/product(s) during the period beginning 29 days before the dose of study vaccine/product or planned use during the study period
• Planned administration/administration of any vaccine within 29 days before study vaccine administration and through Day 43 post-delivery, except seasonal influenza vaccines and dTpa/Tdap or tetanus, which may be administered according to standard of care ≥ 15 days before or after study vaccination
• Administration of immunoglobulins, blood products or plasma derivatives within 3 months before study vaccination or planned administration through Visit 5
• Administration of immune-modifying therapy within 6 months before the study vaccine/product dose, or planned administration through delivery. This includes but is not limited to:

• Azathioprine, mycophenolate mofetil, 6-mercaptopurine, cyclosporine, tacrolimus, monoclonal or polyclonal antibodies;
• Prednisone, ≥ 5 mg/day or equivalent for ≥ 14 days. Topical, steroids are allowed. Inhaled steroids are allowed if ≤ 500µg/day of beclomethasone or fluticasone, or ≤ 800µg/day of budesonide.

Prior/Concomitant clinical study experience

• Previous participation in a clinical trial of an RSV vaccine
• Concurrently participating in another clinical study, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product

Other exclusions

• Alcoholism or substance use disorder within the past 24 months based on the presence of two or more abuse criteria
• A local condition that precludes injection of the study drug or precludes assessment of local reactogenicity
• Consanguinity of maternal subject and her partner (second degree cousins or closer)
• Any study personnel or their immediate dependants, family, or household members

Infant subjects

• Concurrently participating in another clinical study, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product
• Child in care

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Huntington Park, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Nampa, Idaho, United States

GSK Investigational Site

Metairie, Louisiana, United States

GSK Investigational Site

Gulfport, Mississippi, United States

GSK Investigational Site

St Louis, Missouri, United States

GSK Investigational Site

Albuquerque, New Mexico, United States

GSK Investigational Site

Johnson City, New York, United States

GSK Investigational Site

Englewood, Ohio, United States

GSK Investigational Site

Beaumont, Texas, United States

GSK Investigational Site

Fort Worth, Texas, United States

GSK Investigational Site

Plano, Texas, United States

GSK Investigational Site

South Brisbane, Queensland, Australia

GSK Investigational Site

Melbourne, Victoria, Australia

GSK Investigational Site

Halifax, Nova Scotia, Canada

GSK Investigational Site

Québec, , Canada

GSK Investigational Site

Helsinki, , Finland

GSK Investigational Site

Clermont-Ferrand, , France

GSK Investigational Site

Saint-Etienne, , France

GSK Investigational Site

Auckland, , New Zealand

GSK Investigational Site

Wellington, , New Zealand

GSK Investigational Site

Panama City, , Panama

GSK Investigational Site

Panama City, , Panama

GSK Investigational Site

Soweto, Gauteng, South Africa

GSK Investigational Site

Málaga, Andalusia, Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Burgos, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Majadahonda (Madrid), , Spain

GSK Investigational Site

Marbella, , Spain

Countries

United States; Australia; Canada; Finland; France; New Zealand; Panama; South Africa; Spain

References

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.

Reference Type: DERIVED

PMID: 36722147 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-001991-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

209544

Identifier Type: -

Identifier Source: org_study_id