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
Condition: Respiratory Syncytial Virus Infections
MeSH terms: Respiratory Syncytial Virus Infections
Intervention: RSV MAT 60 µg; RSV MAT 120 µg; Placebo
Intervention description: One single dose of RSV MAT 60 µg vaccine administered intramuscularly in the deltoid region of the non-dominant arm on Day 1.; One single dose of RSV MAT 120 µg vaccine administered intramuscularly in the deltoid region of the non-dominant arm on Day 1.; One single dose of placebo (NaCl solution) administered intramuscularly in the deltoid region of the non-dominant arm on Day 1.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: 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.
Enrollment: 534.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

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

          -  Does not plan after delivery to give the infant for adoption or place the infant 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 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