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

NCT ID: NCT04605159

Last Updated: 2025-02-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

11194 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-20

Study Completion Date

2023-06-14

Brief Summary

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The purpose of this study was to evaluate the ability of a single dose of the investigational RSV Maternal vaccine, administered intramuscularly (IM) to pregnant women aged 18-49 years, in good general maternal health, in preventing medically assessed RSV associated Lower Respiratory Tract Illnesses (LRTIs) in infants born to vaccinated mothers. The study also evaluated the safety of the investigational RSV Maternal vaccine both in vaccinated mothers and in their corresponding infant.

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.

Detailed Description

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Conditions

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Respiratory Syncytial Virus Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Following the decision to stop enrollment and vaccination, the study/site staff and maternal participants no longer stayed blinded.

Study Groups

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RSV MAT Group - Mother

Maternal participants received a single dose of the RSV MAT vaccine administered at Day 1 in this study.

Group Type EXPERIMENTAL

RSV MAT

Intervention Type BIOLOGICAL

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

Placebo Group - Mother

Maternal participants received a single dose of placebo administered at Day 1 in this study.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

One dose of placebo (lyophilized sucrose reconstituted with NaCl solution) administered intramuscularly in the non-dominant arm at Day 1.

RSV MAT Group - Infant

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Placebo Group - Infant

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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RSV MAT

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

Intervention Type BIOLOGICAL

Placebo

One dose of placebo (lyophilized sucrose reconstituted with NaCl solution) administered intramuscularly in the non-dominant arm at Day 1.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

49 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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Birmingham, Alabama, United States

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Dothan, Alabama, United States

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Mobile, Alabama, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Burbank, California, United States

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Los Angeles, California, United States

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Miami, Florida, United States

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Blackfoot, Idaho, United States

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Idaho Falls, Idaho, United States

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Nampa, Idaho, United States

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Nampa, Idaho, United States

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Covington, Louisiana, United States

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Lafayette, Louisiana, United States

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Slidell, Louisiana, United States

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Detroit, Michigan, United States

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Saginaw, Michigan, United States

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Missoula, Montana, United States

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Grand Island, Nebraska, United States

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Lincoln, Nebraska, United States

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Albuquerque, New Mexico, United States

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Englewood, Ohio, United States

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Greenville, South Carolina, United States

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Hendersonville, Tennessee, United States

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Arlington, Texas, United States

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Austin, Texas, United States

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Burleson, Texas, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Georgetown, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Keller, Texas, United States

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Lampasas, Texas, United States

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League City, Texas, United States

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McAllen, Texas, United States

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Mesquite, Texas, United States

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Plano, Texas, United States

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Weatherford, Texas, United States

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Norfolk, Virginia, United States

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Buenos Aires, , Argentina

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Ciudad AutOnoma de Buenos Aire, , Argentina

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Ciudad AutOnoma de Buenos Aire, , Argentina

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Córdoba, , Argentina

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San Miguel de Tucumán, , Argentina

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South Brisbane, Queensland, Australia

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Southport, Queensland, Australia

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Clayton, Victoria, Australia

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Geelong, Victoria, Australia

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Nedlands, Western Australia, Australia

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Matlab, , Bangladesh

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Sylhet, , Bangladesh

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Genk, , Belgium

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Ghent, , Belgium

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Kortrijk, , Belgium

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Leuven, , Belgium

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Sint-Niklaas, , Belgium

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Caxias do Sul, , Brazil

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Nova Iguaçu, , Brazil

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Porto Alegre, , Brazil

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RibeirAo PretoSP, , Brazil

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Santa Maria, , Brazil

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São José do Rio Preto, , Brazil

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Halifax, Nova Scotia, Canada

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Kingston, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Barranquilla, , Colombia

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Bogotá, , Colombia

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Cali Colombia, , Colombia

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Chía, , Colombia

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Medellín, , Colombia

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Medellín, , Colombia

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Santo Domingo Este, , Dominican Republic

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Helsinki, , Finland

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Kokkola, , Finland

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Oulu, , Finland

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Tampere, , Finland

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Turku, , Finland

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Bordeaux, , France

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Clermont-Ferrand, , France

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Montpellier, , France

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Paris, , France

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Pierre-Bénite, , France

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Comayagua, , Honduras

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San Pedro Sula, , Honduras

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Kolkata, , India

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Mangalore, , India

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Mysore, , India

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Nagpur, , India

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Pune, , India

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Vadu Budruk Pune, , India

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Bari, , Italy

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Messina, , Italy

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Milan, , Italy

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Milan, , Italy

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Milan, , Italy

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Novara, , Italy

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Palermo, , Italy

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Prato, , Italy

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Verona, , Italy

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Chihuahua City, , Mexico

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Monterrey, , Mexico

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Monterrey, , Mexico

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Morelia, , Mexico

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Oaxaca City, , Mexico

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San Juan del Río, , Mexico

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San Luis Potosí City, , Mexico

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Grafton Auckland, , New Zealand

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Papatoetoe Auckland, , New Zealand

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Wellington, , New Zealand

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Panama City, , Panama

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Panama City, , Panama

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Panama City, , Panama

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Panama City, , Panama

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Cavite, , Philippines

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Manila, , Philippines

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Manila, , Philippines

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Johannesburg, , South Africa

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Pretoria, , South Africa

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Soshanguve, , South Africa

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Soweto, , South Africa

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Daegu, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Aravaca, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Bilbao, , Spain

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Boadilla Del Monte Madrid, , Spain

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Burgos, , Spain

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Getafe, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Marbella, , Spain

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Málaga, , Spain

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Málaga, , Spain

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Seville, , Spain

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Seville, , Spain

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TorrejOn Ardoz Madrid, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Valladolid, , Spain

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Changhua, , Taiwan

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Bangkok, , Thailand

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Chiang Mai, , Thailand

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Edinburgh, , United Kingdom

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Countries

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United States Argentina Australia Bangladesh Belgium Brazil Canada Colombia Dominican Republic Finland France Honduras India Italy Mexico New Zealand Panama Philippines South Africa South Korea Spain Taiwan Thailand United Kingdom

References

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Dieussaert I, Hyung Kim J, Luik S, Seidl C, Pu W, Stegmann JU, Swamy GK, Webster P, Dormitzer PR. RSV Prefusion F Protein-Based Maternal Vaccine - Preterm Birth and Other Outcomes. N Engl J Med. 2024 Mar 14;390(11):1009-1021. doi: 10.1056/NEJMoa2305478.

Reference Type BACKGROUND
PMID: 38477988 (View on PubMed)

Banooni P, Gonik B, Epalza C, Reyes O, Madhi SA, Gomez-Go GD, Zaman K, Llapur CJ, Lopez-Medina E, Stanley T, Kantele A, Huang LM, Mussi-Pinhata MM, Dewulf J, Langley JM, Seidl C, Ota M, Kirabo M, Anspach B, Dieussaert I, Henry O, Kim JH, Picciolato M. Efficacy, immunogenicity, and safety of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine. Clin Infect Dis. 2025 Jan 29:ciaf033. doi: 10.1093/cid/ciaf033. Online ahead of print.

Reference Type DERIVED
PMID: 39879629 (View on PubMed)

Ginsburg AS, Srikantiah P. Respiratory syncytial virus: promising progress against a leading cause of pneumonia. Lancet Glob Health. 2021 Dec;9(12):e1644-e1645. doi: 10.1016/S2214-109X(21)00455-1. Epub 2021 Nov 11. No abstract available.

Reference Type DERIVED
PMID: 34774184 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2020-001355-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

212171

Identifier Type: -

Identifier Source: org_study_id

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