A Phase III Double-blind Study to Assess Safety and Efficacy of an RSV Maternal Unadjuvanted Vaccine, in Pregnant Women and Infants Born to Vaccinated Mothers (GRACE)

This is an interventional prevention trial for Respiratory Syncytial Virus Infections Read More

Inclusion Criteria:

Maternal participants

• Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Participants who give written or witnessed/thumb printed informed consent after the study has been explained, and before any study specific procedures are performed, as per local regulations regulatory requirements.
• Age 18 to 49 years, inclusive, at the time of study intervention.
• Pre-pregnancy BMI 17.0 to 39.9 kg/m2, inclusive.
• In good general maternal health as established by medical history and clinical examination before entering into the study.
• Singleton pregnancy (including instances where the singleton pregnancy derives from a vanishing twin syndrome).
• At 24^0/7 to 34^0/7 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) i.e. at or before 28 weeks of gestation.
• 1st or 2nd 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.
• No fetal genetic abnormalities (based on genetic testing, if performed).
• No significant congenital malformations, as assessed by fetal anomaly ultrasound scan conducted at or beyond 18 weeks of gestation.
• Willing to provide cord blood.
• Who do not plan to give their child for adoption.
• Who plan to reside in the study area for at least one year after delivery.
• Willing to have the infant followed-up after delivery for a period of 12 months.

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 study specific procedure. OR, if permitted by local regulation, documented verbal consent for infant's participation obtained from the parent(s)/LAR(s) at birth, followed by written consent obtained by (or before) Visit 2-newborn.

Exclusion Criteria:

Maternal participants 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:
• Gestational hypertension unless blood pressure it is controlled and maintained in the normal range (<140mmHg and <90mmHg) through diet and/or antihypertensive medications
• Gestational diabetes not controlled by medication, diet and/or exercise
• Pre-eclampsia
• Eclampsia
• Intrauterine Growth Restriction/Fetal Growth Restriction
• Placenta previa
• Placental abruption, placenta accreta/percreta/increta, chorioamnionitis or any abnormalities that can impair the maternal-fetal circulation
• Polyhydramnios
• Oligohydramnios
• Preterm labour or history of preterm labour in the current pregnancy
• Any intervention to prevent preterm delivery or medical treatment for suspected preterm delivery, including administration of systemic corticosteroids for fetal lung maturation
• Cholestasis
• Other pregnancy-related complications (per investigator's judgement)
• Significant structural abnormalities of the uterus or cervix
• History of 2 or more prior stillbirths or neonatal deaths/history of 2 or more preterm births at ≤34 weeks gestation/3 or more consecutive spontaneous abortions
• Known HIV infection (as per serological tests performed during the current pregnancy)
• Known or suspected HBV or HCV infection
• Known or suspected infection during the current pregnancy with Toxoplasma, Parvovirus B19, Syphilis, Zika, Rubella, Varicella, CMV or primary genital Herpes Simplex
• Active infection with tuberculosis
• Known or suspected impairment of the immune system
• Current autoimmune disorder for which the participant has received immune-modifying therapy within 6 months before study vaccination, or plans administration through delivery
• Lymphoproliferative disorder or malignancy within 5 years before study vaccination
• Acute or chronic clinically significant abnormality or poorly controlled pre-existent co-morbidities or any other clinical conditions that might pose additional risk to the participant due to participation in the study
• Any conditions that may interfere with participant'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 an RSV vaccine in the current pregnancy
• Use of any investigational/non-registered product other than the study vaccine/product as described below, or planned use during the period :
• For a drug, vaccine or medical device: from 29 days before the dose of study vaccine
• For immunoglobulins: 3 months before the dose of study vaccine/product.

The exception to this is investigational products administered in the setting of a pandemic which may be allowed following delivery

• Planned administration/administration of any vaccine from 29 days before the dose of study vaccine or planned administration through delivery, except:
• Seasonal influenza vaccines, tetanus vaccines, dTpa/Tdap - alone vaccines, dTpa/Tdap vaccines that also contain other antigens, Hepatitis B vaccines, and COVID-19 vaccines all of which may be administered according to standard of care ≥15 days before or after study vaccination
• Administration of immunoglobulins (except anti-Rh0D IG, which may be administered at any time), blood products or plasma derivatives within 3 months before study vaccination or planned administration through delivery
• Administration of immune-modifying therapy within 6 months before the study vaccination, 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; Inhaled, intra-articular/intra-bursal and topical steroids are allowed
• Corticosteroids administered for fetal lung maturation

Prior/Concurrent clinical study experience

- Concurrently participating in another clinical study, in which the participant 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 DSM-5 criteria
• A local condition that precludes injection of the study vaccine/product or precludes assessment of local reactogenicity
• Consanguinity of maternal participant and her partner (second degree cousins or closer)
• Any study personnel or their immediate dependants, family or household members

Infant participants

• Concurrently participating in another clinical study, 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.