Respiratory Syncytial Virus InfectionsPhase 3NCT02624947
A Study to Determine the Safety and Efficacy of the RSV F Vaccine to Protect Infants Via Maternal Immunization
A Phase 3 study testing RSV F vaccine with adjuvant and Formulation buffer in people with Respiratory Syncytial Virus Infections, run by Novavax at 88 sites in 11 countries.
Trial summary
The purpose of this study is to determine the efficacy of maternal immunization during the third trimester of pregnancy with the RSV F vaccine against medically-significant RSV lower respiratory tract infection (LRTI), as defined by hypoxemia or tachypnea at rest, through the first 90, 120, 150, and 180 days of life… Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Respiratory Syncytial Virus Infections
- What is being tested?
- RSV F vaccine with adjuvant and Formulation buffer
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4,636 participants
- Where
- 88 sitesin 11 countries
- Study dates
- Dec 2015to 12 Jul 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- ≥18 and ≤40 years-of-age
- Singleton pregnancy of 28 to 36 0/7 weeks gestation on the day of planned vaccination
- Documentation of gestational age will be based on one of the following composite criteria. (Note: The Investigator was to use the earliest ultrasound data available to establish the study-specific gestational age dating):
- Gestational Age Dating Based on First Trimester Data (data obtained ≤13 6/7 weeks): The date of the first day of the reported last menstrual period (LMP) may be used to establish the gestational age if corroborated by a first trimester ultrasound. If the gestational age estimation derived using the LMP and the first trimester ultrasound are discrepant >7 days, the ultrasound will be used to establish gestational age. If LMP is uncertain or unknown, the ultrasound-established gestational age estimation will be used to establish the gestational age of the pregnancy.
- Gestational Age Dating Based on Early Second Trimester Data (data obtained 14 0/7 to 21 6/7 weeks): The day of the first reported LMP may be used to establish the gestational age if corroborated by an early second trimester ultrasound (that estimates the gestational age between 14 0/7 and 21 6/7 weeks). If the gestational age estimation derived using the LMP and the early second trimester ultrasound are discrepant >10 days, the ultrasound will be used to establish the gestational age. If LMP is uncertain or unknown, the ultrasound-established gestational age estimation will be used to establish the gestational age of the pregnancy.
- Gestation Age Dating Based on Later Second Trimester Data (data obtained 22 0/7 and 27 6/7 weeks by LMP): The date of the first day of the reported LMP may be used to establish the gestation age if corroborated by a later second trimester ultrasound (that estimates the gestational age between 22 0/7 and 27 6/7 weeks). If the gestational age estimation derived using the LMP and the later second trimester ultrasound are discrepant >14 days, the ultrasound will be used to establish the gestational age. If LMP is uncertain or unknown, the ultrasound-established gestational age estimation will be used to establish the gestational age of the pregnancy.
Show all 16Show fewer
- Gestational Age Dating When the LMP is Uncertain or Unknown AND No Prior First or Second Trimester Ultrasound Has Been Performed: An ultrasound performed at screening within the second trimester (≤27 6/7 weeks) will be used to establish the gestational age of the pregnancy.
- Documentation of a second or third (between 18 0/7 weeks and prior to randomization) trimester ultrasound with no major fetal anomalies identified.
- Good general maternal health as demonstrated by:
- Medical history (including history of adverse reactions to prior vaccines and allergies).
- Physical examination including at least vital signs (blood pressure, pulse, respirations, and oral temperature); weight; height; examination of the HEENT, cardiovascular, pulmonary, gastrointestinal (abdominal), musculoskeletal, lymphatic, and dermatologic organ systems; and documentation of fetal heart tones. Note that abnormal vital signs may be repeated at the investigator's discretion since these measures may be labile. Vital signs should be assessed in the context of normal values for the third trimester of pregnancy (see the Study Operations Manual).
- Clinical laboratory parameters that include:
- For the first year of study conduct in any country, normal/clinically insignificant blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase (ALP), hemoglobin, white blood count, and platelet count. Note that normal ranges for clinical laboratory parameters will be based on reference ranges appropriate for the subject population under study (i.e., third trimester of pregnancy) and as defined in the toxicity grading scale (TGS) (see the Study Operations Manual).
- For all subjects, serologic exclusion of infection with hepatitis B (HBV) and C (HCV) viruses, syphilis, and HIV as documented by testing (performed at the central or local laboratory) at screening or by medical records during the current pregnancy.
- Able to understand, and both willing and physically able to comply with study procedures. This includes anticipation of reasonable geographic proximity to the study clinic and adequate transportation to comply with scheduled and unscheduled study follow-up visits.
- Able and willing to provide written informed consent for themselves and infant.
Who cannot join
- Symptomatic cardiac or pulmonary disease requiring chronic drug therapy, including hypertension and asthma. Asthma will be exclusionary if the subject is receiving chronic systemic glucocorticoids at any dose or inhaled glucocorticoids at any dose >500µg per day of beclomethasone or fluticasone, or >800μg per day of budesonide.
- Pregnancy complications (in the current pregnancy) such as preterm labor, hypertension (blood pressure [BP] >140/90 in the presence of proteinuria or BP >150/100 with or without proteinuria) or currently on an antihypertensive therapy or pre-eclampsia; or evidence of intrauterine growth restriction.
- Grade 2 or higher clinical laboratory or vital sign abnormality. Exclusion of subjects with grade 1 abnormalities will be based on the subject's prior medical history and the investigator's clinical judgment that the abnormality is indicative of a meaningful physiologic event.
- Receipt of any licensed vaccine (e.g., Tdap, inactivated influenza vaccine) within 14 days of study vaccination.
- Received any RSV vaccine at any time.
- Body mass index (BMI) of ≥40, at the time of the screening visit.
Show all 30Show fewer
- Hemoglobinopathy (even if asymptomatic) or blood dyscrasias.
- Hepatic or renal dysfunction.
- Established diagnosis of seizure disorder, regardless of therapy.
- Known, active auto-immune disease or immunodeficiency syndrome.
- Endocrine disorders, including (but not limited to) untreated hyperthyroidism, untreated hypothyroidism (unless due to auto-immune disease), and glucose intolerance (e.g., diabetes mellitus type 1 or 2) antedating pregnancy, or occurring during pregnancy and requiring interventions other than diet for control.
- History of major gynecologic or major abdominal surgery, including bariatric surgery (previous Caesarean section is not an exclusion).
- Known HIV, syphilis, HBV, or HCV infection, as assessed by serologic tests conducted during the current pregnancy or as a procedure during the screening period of the study.
- Primary genital Herpes simplex virus (HSV) infection during the current pregnancy.
- Current alcohol or drug abuse based on the Investigator's knowledge of present or recent (within the last 2 years) use/abuse of alcohol or illegal or non-prescription drugs.
- Documentation that the current pregnancy results from in vitro fertilization (IVF).
- Documentation that the current pregnancy results from rape or incest.
- Documentation that the infant will be a ward of the state or be released for adoption.
- History/presence of deep venous thrombosis or thromboembolism, or the use of anticoagulants during pregnancy (the use of low-dose aspirin as prophylaxis [e.g., for the prevention of morbidity and mortality from preeclampsia] is acceptable is dosages consistent with local standards of care).
- Red blood cell allo-immunization.
- Prior stillbirth or neonatal death, or multiple (≥3) spontaneous abortions.
- Prior preterm delivery ≤34 weeks gestation or having ongoing intervention (medical/surgical) in current pregnancy to prevent preterm birth.
- Greater than five (5) prior deliveries.
- Previous infant with a known genetic disorder or major congenital anomaly.
- Receipt of investigational drugs or immune globulins (with the exception of prophylactic anti-Rho D immune globulin) within six (6) months prior to the administration of the study vaccine.
- Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the study vaccine. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose ≥10mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted except for the limit established in exclusion criterion #1.
- Neuro-psychiatric illness deemed likely to interfere with protocol compliance, safety reporting, or receipt of pre-natal care; or requiring treatment with psychotropic drugs (excluding treatment for depression and anxiety).
- Any other physical, psychiatric or social condition which may, in the investigator's opinion, increase the risks of study participation to the maternal subject or the fetus/infant; or may lead to the collection of incomplete or inaccurate safety data.
- Acute disease within 72 hours of the day of the planned vaccination (defined as the presence of a moderate or severe illness with or without fever, or an oral temperature >38.0°C).
- History of a serious adverse reactions (e.g., anaphylaxis) to any prior vaccine.
Trial locations and contacts
88 sites in 11 countries.
88 sites in 11 countries
United States49 sites
Research Site US126
Alexandria, Louisiana, 71301
Research Site US038
Augusta, Kansas, 67010
Research Site US134
Aurora, Colorado, 80045
Research Site US116
Beaumont, Texas, 77702
Research Site US098
Biloxi, Mississippi, 39531
Research Site US115
Birmingham, Alabama, 35233
Research Site US037
Blackfoot, Idaho, 83221
Research Site US095
Chicago, Illinois, 60611
Research Site US092
Colton, California, 92324
Research Site US035
Cullman, Alabama, 35058
Research Site US036
Denver, Colorado, 80204
Research Site US101
Detroit, Michigan, 48235
Research Site US020
Durham, North Carolina, 27710
Research Site US089
Englewood, Ohio, 45322
Research Site US097
Fort Bragg, North Carolina, 28310
Research Site US130
Fort Defiance, Arizona, 86504
Research Site US083
Fort Worth, Texas, 77555
Research Site US131
Gallup, New Mexico, 87301
Research Site US043
Galveston, Texas, 77555
Research Site US019
Houston, Texas, 77030
Research Site US128
Houston, Texas, 77036
Research Site US114
Huntington Park, California, 90255
Research Site US031
Hutchinson, Kansas, 67502
Research Site US119
Idaho Falls, Idaho, 83404
Research Site US087
Johnson City, New York, 13790
Research Site US125
Lampasas, Texas, 76550
Research Site US102
Lincoln, Nebraska, 68516
Research Site US094
Longview, Texas, 75605
Research Site US127
Los Angeles, California, 90057
Research Site US096
Louisville, Kentucky, 40202
Research Site US091
Madera, California, 93637
Research Site US039
Metairie, Louisiana, 70006
Research Site US032
Nampa, Idaho, 83687
Research Site US088
Neptune City, New Jersey, 07753
Research Site US025
Norfolk, Nebraska, 68701
Research Site US123
Phoenix, Arizona, 85004
Research Site US021
Pittsburgh, Pennsylvania, 15213
Research Site US100
Richmond, Virginia, 23220
Research Site US093
Riverside, California, 94201
Research Site US121
Salt Lake City, Utah, 84107
Research Site US008
Salt Lake City, Utah, 84124
Research Site US099
Salt Lake City, Utah, 84132
Research Site US042
San Antonio, Texas, 78229
Research Site US041
Seattle, Washington, 98105
Research Site US086
Syracuse, New York, 13210
Research Site US103
Tucson, Arizona, 85712
Research Site US040
Washington D.C., District of Columbia, 20010
Research Site US090
West Des Moines, Iowa, 50266
Research Site US129
Whiteriver, Arizona, 85941
South Africa10 sites
Research Site ZA010
Bellville, Western Cape, 7553
Research Site ZA006
Benoni, 1500
Research Site ZA008
Bloemfontein, 9301
Research Site ZA003
Hillbrow, Johannesburg, 2001
Research Site ZA009
Paarl, Western Cape, 7646
Research Site ZA004
Parow, Cape Town, 7505
Research Site ZA002
Soshanguve, 0152
Research Site ZA001
Soweto, 2013
Research Site ZA007
Thabazimbi, Limpopo Providence, 0380
Research Site ZA011
Worcester, Western Cape, 6850
Argentina5 sites
Research Site AR002
Buenos Aires, C1426BOR
Research Site AR006
Córdoba, 5000
Research Site AR011
Mendoza, 5500
Research Site AR008
Salta, 4400
Research Site AR003
San Miguel de Tucumán, 4000
Australia5 sites
Research Site AU007
Adelaide, South Australia, 5006
Research Site AU010
Brisbane, Queensland, 4101
Research Site AU011
Clayton, Victoria, 3148
Research Site AU008
Melbourne, Victoria, 3010
Research Site AU009
Perth, Western Australia, 6008
New Zealand4 sites
Research Site NZ002
Christchurch, 8140
Research Site NZ003
Grafton, Auckland, 1010
Research Site NZ001
Papatoetoe, Aukland, 2025
Research Site NZ004
Wellington, 6021
Spain4 sites
Research Site ES002
Barcelona, 08035
Research Site ES003
Madrid, 28046
Research Site ES004
Santiago de Compostela, 15706
Research Site ES001
Seville, 41012
United Kingdom4 sites
Research Site UK004
Bristol, BS2 8EG
Research Site UK001
London, SW17 0RE
Research Site UK002
Oxford, OX3 7LE
Research Site UK003
Southampton, SO16 6YD
Chile3 sites
Research Site CL003
Concepción, Biobio, 4070038
Research Site CL002
Osorno, Los Lagos Region, 5311523
Research Site CL001
Santiago, Region Metropolitana (RM), 8360160
Philippines2 sites
Research Site PH001
Alabang, Manila, 1781
Research Site PH002
Muntinlupa, National Capital Region, 1781
About this study
Official title: A Phase 3, Randomized, Observer-Blind, Placebo-Controlled, Group-Sequential Study to Determine the Immunogenicity and Safety of a Respiratory Syncytial Virus (RSV) F Nanoparticle Vaccine With Aluminum in Healthy Third-trimester Pregnant Women; and Safety and Efficacy of Maternally Transferred Antibodies in Preventing RSV Disease in Their Infants
The purpose of this study is to determine the efficacy of maternal immunization during the third trimester of pregnancy with the RSV F vaccine against medically-significant RSV lower respiratory tract infection (LRTI), as defined by hypoxemia or tachypnea at rest, through the first 90, 120, 150, and 180 days of life in infants.
Read the detailed description
This is a randomized, observer-blind, placebo-controlled trial enrolling third-trimester pregnant women in the Northern and Southern hemispheres, for up to four consecutive RSV seasons in each hemisphere. The trial could enroll up to 8618 third-trimester pregnant subjects, of which 4,636 were actually enrolled. Women in the third trimester of a singleton uncomplicated low-risk pregnancy and 18 to 40 years of age (inclusive) were enrolled and randomized in a 1:1 ratio into one of two treatment groups, active or placebo, over approximately three months prior to peak RSV season in their locale. After the first global season of enrollment, the randomization scheme was changed to a 2:1 (active/placebo) ratio to enable a more efficient accrual of the safety database.
All maternal subjects were to receive a single intramuscular (IM) injection on Day 0 with the assigned test article, the RSV F vaccine, or placebo. Study participation for maternal subjects spanned approximately nine (9) months from the first dose, ending six (6) months post-delivery. Study follow-up for live-born infant subjects spanned approximately one (1) year post-delivery.
- Conditions
- Respiratory Syncytial Virus Infections
- Being tested
- RSV F vaccine with adjuvant, Formulation buffer
- Keywords
- RSV
- Medical subject headings
- Respiratory Syncytial Virus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RSV F vaccine with adjuvantBiological
Formulation bufferBiological
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group A | Placebo comparator | Formulation buffer (0.5mL injection) Receives: Biological: Formulation buffer |
| Treatment Group | Active comparator | RSV F vaccine with adjuvant (0.5mL injection) Receives: Biological: RSV F vaccine with adjuvant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infants: Percentages of Participants With Medically Significant RSV LRTI With Either Hypoxemia (SpO2 <95% at Sea Level or <92% at Altitudes >1800 Meters) or Tachypnea
Percentages of infants with medically-significant RSV LRTI from delivery through 90, 120,150, and 180 days of life, as defined by:
- The presence of RSV infection confirmed by detection of RSV genome by RT-PCR on respiratory secretions (obtained within the continuous illness episode which fulfills the other criteria listed below); AND
- At least one manifestation of lower respiratory tract infection (LRTI) from among the following: cough, nasal flaring, lower chest wall indrawing, subcostal retractions, stridor, rales, rhonchi, wheezing, crackles/crepitations, or observed apnea; AND
- Evidence of medical significance as defined by the presence of:
- EITHER hypoxemia (peripheral oxygen saturation [SpO2] < 95% at sea level or < 92% at altitudes > 1800 meters) OR
- Tachypnea (≥ 70 breaths per minute [bpm] in infants 0 to 59 days of age and ≥ 60 bpm in infants ≥ 60 days of age).
Measured: Delivery to 180 days after delivery
Secondary outcomes (24)
Infants: Number of Participants With RSV LRTI With Severe Hypoxemia (Sp02 <92% at Sea Level or <87% at Altitudes >1800 Meters) or Documented Use of Oxygen by High Flow Nasal Cannula or Other Advanced Respiratory Support Through 90 Days of Life
The number of infants with RSV LRTI with EITHER severe hypoxemia (SpO2 < 92% at sea level or < 87% at altitudes > 1800 meters) OR the documented use of oxygen by high flow nasal cannula OR CPAP OR BiPAP OR Bubble CPAP OR bag-mask ventilation OR intubation with subsequent mechanical (or manual) ventilation OR ECMO from delivery through 90, 120, 150, and 180 days of life.
Measured: Delivery to 180 days after delivery
Infants: Percentages of Participants With RSV LRTI With Hospitalization From Delivery
Percentages of infants with RSV LRTI with hospitalization from delivery through 90, 120, 150, and 180 days of life.
Measured: Delivery to 180 days after delivery
Infant: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Neonatal Period and Through the First Year of Life
Number of infants with AEs and SAEs (with special attention to congenital anomalies; respiratory failure other than RSV-associated hospitalization; neonatal death; infant death; sudden infant death syndrome; asphyxia; neonatal or hypoxic-ischemic encephalopathy; or other adverse events or complications of adverse events that necessitate hospitalization) during the neonatal period and through the first year of life.
Measured: Delivery to 364 days after delivery
Infants: Number of Participants With Potential Developmental Delay
Number of infants with potential developmental delay (a term used to describe a delay in a child's development), as measured by the outcome of testing with the Ages and Stages Questionnaire-3 at 6 months and at 1 year, in infants of RSV F vaccinees as compared to placebo.
Measured: Day 180 after delivery
Maternal: Number of Participants With Solicited Injection Site and Systemic Reactogenicity
A number of maternal participants with solicited injection site and systemic reactogenicity within seven days of vaccination.
Measured: Day 0 to Day 7
Maternal: Number of Participants With Unsolicited Adverse Events, Medically-attended Adverse Events (MAEs), Significant New Medical Conditions (SNMCs) and Serious Adverse Events (SAEs)
Number of maternal participants with unsolicited (local and systemic) adverse events (AEs), unscheduled medically-attended adverse events (MAEs), significant new medical conditions (SNMCs), and serious adverse events (SAEs) through delivery and six (6) months thereafter.
Measured: Delivery to 180 days after delivery
Maternal: Number of Participants With Caesarean, Vaginal, or Instrument Assisted Vaginal Modes of Delivery
Number of maternal subjects that had either Caesarean, vaginal, or instrument-assisted vaginal modes of delivery.
Measured: Delivery
Maternal: Immunogenicity of RSV F Vaccine and Placebo Expressed as GMFR
Immunogenicity of RSV F Vaccine and Placebo (Anti-F IgG, PCA, and RSV Types A and B - MN assays) among Maternal Participants from Day 14 until Delivery
Measured: Day 14 to Delivery
Maternal: Percentage of Participants With a Seroresponse to RSV F Vaccine and Placebo
Immunogenicity of RSV F Vaccine and Placebo (Anti-F IgG, PCA, and RSV Types A and B - MN assays) among Maternal Participants from Day 14 until Delivery
Measured: Day 14 to Delivery
Maternal: Percentage of Participants Who Seroconverted (2 Fold Increase) as Determined by Immunogenicity of RSV F Vaccine and Placebo
Immunogenicity of RSV F Vaccine and Placebo (Anti-F IgG, PCA, and RSV Types A and B - MN assays) among Maternal Participants from Day 14 until Delivery
Measured: Day 14 to Delivery
Maternal: Percentage of Participants Who Seroconverted (4 Fold Increase) as Determined by Immunogenicity of RSV F Vaccine and Placebo
Immunogenicity of RSV F Vaccine and Placebo (Anti-F IgG, PCA, and RSV Types A and B - MN assays) among Maternal Participants from Day 14 until Delivery
Measured: Day 14 to Delivery
Immunogenicity of RSV F Vaccine and Placebo Expressed as GMT
Immunogenicity of RSV F Vaccine and Placebo (Anti-F IgG, PCA, and RSV Types A and B - MN assays) among Infant Participants from Delivery until Day 180
Measured: Delivery to Day 180
Infants: Percentage of Participants With a Seroresponse to RSV F Vaccine and Placebo
Immunogenicity of RSV F Vaccine and Placebo (Anti-F IgG, PCA, and RSV Types A and B - MN assays) among Infant Participants from Delivery until Day 180
Measured: Delivery to Day 180
Infant: Immunogenicity of RSV F Vaccine and Placebo Expressed as GMR
Immunogenicity of RSV F Vaccine and Placebo (Anti-F IgG, PCA, and RSV Types A and B - MN assays) among Infant Participants from Day 14 until Day 180
Measured: Day 14 to Day 180
Infants: Mean Length of Participants at Birth
Length of Infant participants measured at delivery expressed in centimeters
Measured: At Delivery
Infants: Mean Weight of Participants at Birth
Weight of infant participants measured at delivery expressed in kilograms.
Measured: At Delivery
Infants: Mean Frontal-occipital Head Circumference of Participants at Birth
Frontal-occipital Head Circumference measured in infant participants at delivery expressed as centimeters
Measured: At Delivery
Infants: Mean APGAR (Appearance, Pulse, Grimace, Activity, Respiration) Score of Participants at Birth
The APGAR test measures the infant's Appearance, Pulse, Grimace, Activity, and Respiration. Any score of 7 or above is considered a good APGAR score.
The maximum APGAR score is 10 and the minimum score is 1.
Measured: At Delivery
Maternal: Number of Participants With Post-immunization Onset of Specific Complications of Third-trimester Pregnancy and Delivery
Number of maternal participants with post-immunization onset of specific complications of third-trimester pregnancy and delivery including Pregnancy complications, Labor and delivery complications.
Measured: Day 0 to Delivery
Infants: Number of Participants With Developmental Delay
Number of infants with developmental delay (a term used to describe a delay in a child's development.), as measured by the outcome of testing at 1 year, in infants of RSV F vaccinees as compared to placebo.
Measured: Day 364 after delivery
Maternal: Immunogenicity of Anti-RSV F IgG and Placebo Expressed as GMEU (Geometric Mean ELISA Units/mL)
Immunogenicity of RSV F Vaccine and Placebo (Anti-F IgG) among Maternal Participants from Screening until Delivery
Measured: Pre-dose to Delivery +180 days
Maternal: Immunogenicity of RSV F Vaccine and Placebo Expressed as GMC (Geometric Mean Concentration)
Immunogenicity of RSV F Vaccine and Placebo (Palivizumab-competitive antibodies (PCA)) among Maternal Participants from Screening until Delivery
Measured: Pre-dose to Delivery +180 days
Maternal: Immunogenicity of RSV F Vaccine and Placebo Expressed as GMT (Geometric Mean Titers)
Immunogenicity of RSV F Vaccine and Placebo (RSV/A microneutralization titers expressed as GMT) among Maternal Participants from Screening until Delivery
Measured: Pre-dose to Delivery +180 days
Maternal: Immunogenicity of RSV F Vaccine and Placebo Expressed as GMTs
Immunogenicity of RSV F Vaccine and Placebo (RSV/B microneutralization titers expressed as GMT) among Maternal Participants from Screening until Delivery
Measured: Pre-dose to Delivery +180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2015 (estimated)
- Study startDec 2015
- Primary completion28 Dec 2018
- Study completion12 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Respiratory Syncytial Virus InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 4,636 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novavax
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bill and Melinda Gates Foundation
- Responsible party
- Sponsor
- Investigators
- Clinical Development, Study director, Novavax Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02624947
- Sponsor's protocol ID
- RSV-M-301
- Status last verified
- Apr 2025
- First submitted
- 4 Dec 2015
- Last updated
- 6 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Madhi SA, Polack FP, Piedra PA, Munoz FM, Trenholme AA, Simoes EAF, Swamy GK, Agrawal S, Ahmed K, August A, Baqui AH, Calvert A, Chen J, Cho I, Cotton MF, Cutland CL, Englund JA, Fix A, Gonik B, Hammitt L, Heath PT, de Jesus JN, Jones CE, Khalil A, Kimberlin DW, Libster R, Llapur CJ, Lucero M, Perez Marc G, Marshall HS, Masenya MS, Martinon-Torres F, Meece JK, Nolan TM, Osman A, Perrett KP, Plested JS, Richmond PC, Snape MD, Shakib JH, Shinde V, Stoney T, Thomas DN, Tita AT, Varner MW, Vatish M, Vrbicky K, Wen J, Zaman K, Zar HJ, Glenn GM, Fries LF; Prepare Study Group. Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants. N Engl J Med. 2020 Jul 30;383(5):426-439. doi: 10.1056/NEJMoa1908380.
PubMed 32726529
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Observer-Blind, Placebo-Controlled, Group-Sequential Study to Determine the Immunogenicity and Safety of a Respiratory Syncytial Virus (RSV) F Nanoparticle Vaccine With Aluminum in Healthy Third-trimester Pregnant Women; and Safety and Efficacy of Maternally Transferred Antibodies in Preventing RSV Disease in Their Infants
- ClinicalTrials.gov ID
- NCT02624947
- Acronym / sponsor ID
- RSV-M-301
- Conditions
- Respiratory Syncytial Virus Infections
- Keywords
- RSV
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4,636 participants (actual)
- Lead sponsor
- NovavaxIndustry (pharma, biotech, devices)
- Collaborators
- Bill and Melinda Gates Foundation
- Study start
- Dec 2015
- Primary completion
- 28 Dec 2018 (actual)
- Study completion
- 12 Jul 2019 (actual)
- First posted
- 9 Dec 2015 (estimated)
- Results
- Posted 6 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the efficacy of maternal immunization during the third trimester of pregnancy with the RSV F vaccine against medically-significant RSV lower respiratory tract infection (LRTI), as defined by hypoxemia or tachypnea at rest, through the first 90, 120, 150, and 180 days of life in infants.
Detailed description
This is a randomized, observer-blind, placebo-controlled trial enrolling third-trimester pregnant women in the Northern and Southern hemispheres, for up to four consecutive RSV seasons in each hemisphere. The trial could enroll up to 8618 third-trimester pregnant subjects, of which 4,636 were actually enrolled. Women in the third trimester of a singleton uncomplicated low-risk pregnancy and 18 to 40 years of age (inclusive) were enrolled and randomized in a 1:1 ratio into one of two treatment groups, active or placebo, over approximately three months prior to peak RSV season in their locale. After the first global season of enrollment, the randomization scheme was changed to a 2:1 (active/placebo) ratio to enable a more efficient accrual of the safety database.
All maternal subjects were to receive a single intramuscular (IM) injection on Day 0 with the assigned test article, the RSV F vaccine, or placebo. Study participation for maternal subjects spanned approximately nine (9) months from the first dose, ending six (6) months post-delivery. Study follow-up for live-born infant subjects spanned approximately one (1) year post-delivery.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Group A | Placebo comparator | Biological: Formulation bufferFormulation buffer (0.5mL injection) |
| Treatment Group | Active comparator | Biological: RSV F vaccine with adjuvantRSV F vaccine with adjuvant (0.5mL injection) |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- ≥18 and ≤40 years-of-age
- Singleton pregnancy of 28 to 36 0/7 weeks gestation on the day of planned vaccination
- Documentation of a second or third (between 18 0/7 weeks and prior to randomization) trimester ultrasound with no major fetal anomalies identified.
- Good general maternal health as demonstrated by:
- Able to understand, and both willing and physically able to comply with study procedures. This includes anticipation of reasonable geographic proximity to the study clinic and adequate transportation to comply with scheduled and unscheduled study follow-up visits.
Key exclusion criteria (30 listed)
- Symptomatic cardiac or pulmonary disease requiring chronic drug therapy, including hypertension and asthma. Asthma will be exclusionary if the subject is receiving chronic systemic glucocorticoids at any dose or inhaled glucocorticoids at any dose >500µg per day of beclomethasone or fluticasone, or >800μg per day of budesonide.
- Pregnancy complications (in the current pregnancy) such as preterm labor, hypertension (blood pressure [BP] >140/90 in the presence of proteinuria or BP >150/100 with or without proteinuria) or currently on an antihypertensive therapy or pre-eclampsia; or evidence of intrauterine growth restriction.
- Grade 2 or higher clinical laboratory or vital sign abnormality. Exclusion of subjects with grade 1 abnormalities will be based on the subject's prior medical history and the investigator's clinical judgment that the abnormality is indicative of a meaningful physiologic event.
- Receipt of any licensed vaccine (e.g., Tdap, inactivated influenza vaccine) within 14 days of study vaccination.
- Received any RSV vaccine at any time.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RSV F vaccine with adjuvant | Biological | Treatment Group |
| Formulation buffer | Biological | Treatment Group A |
Primary outcome
Infants: Percentages of Participants With Medically Significant RSV LRTI With Either Hypoxemia (SpO2 <95% at Sea Level or <92% at Altitudes >1800 Meters) or Tachypnea
Time frame: Delivery to 180 days after delivery
Percentages of infants with medically-significant RSV LRTI from delivery through 90, 120,150, and 180 days of life, as defined by: * The presence of RSV infection confirmed by detection of RSV genome by RT-PCR on respiratory secretions (obtained within the continuous illness episode which fulfills the other criteria listed below); AND * At least one manifestation of lower respiratory tract infection (LRTI) from among the following: cough, nasal flaring, lower chest wall indrawing, subcostal retractions, stridor, rales, rhonchi, wheezing, crackles/crepitations, or observed apnea; AND * Evidence of medical significance as defined by the presence of: * EITHER hypoxemia (peripheral oxygen saturation [SpO2] < 95% at sea level or < 92% at altitudes > 1800 meters) OR * Tachypnea (≥ 70 breaths per minute [bpm] in infants 0 to 59 days of age and ≥ 60 bpm in infants ≥ 60 days of age).
24 secondary outcomes
Infants: Number of Participants With RSV LRTI With Severe Hypoxemia (Sp02 <92% at Sea Level or <87% at Altitudes >1800 Meters) or Documented Use of Oxygen by High Flow Nasal Cannula or Other Advanced Respiratory Support Through 90 Days of Life
Time frame: Delivery to 180 days after delivery
Infants: Percentages of Participants With RSV LRTI With Hospitalization From Delivery
Time frame: Delivery to 180 days after delivery
Infant: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Neonatal Period and Through the First Year of Life
Time frame: Delivery to 364 days after delivery
Infants: Number of Participants With Potential Developmental Delay
Time frame: Day 180 after delivery
Maternal: Number of Participants With Solicited Injection Site and Systemic Reactogenicity
Time frame: Day 0 to Day 7
Maternal: Number of Participants With Unsolicited Adverse Events, Medically-attended Adverse Events (MAEs), Significant New Medical Conditions (SNMCs) and Serious Adverse Events (SAEs)
Time frame: Delivery to 180 days after delivery
Maternal: Number of Participants With Caesarean, Vaginal, or Instrument Assisted Vaginal Modes of Delivery
Time frame: Delivery
Maternal: Immunogenicity of RSV F Vaccine and Placebo Expressed as GMFR
Time frame: Day 14 to Delivery
Maternal: Percentage of Participants With a Seroresponse to RSV F Vaccine and Placebo
Time frame: Day 14 to Delivery
Maternal: Percentage of Participants Who Seroconverted (2 Fold Increase) as Determined by Immunogenicity of RSV F Vaccine and Placebo
Time frame: Day 14 to Delivery
Maternal: Percentage of Participants Who Seroconverted (4 Fold Increase) as Determined by Immunogenicity of RSV F Vaccine and Placebo
Time frame: Day 14 to Delivery
Immunogenicity of RSV F Vaccine and Placebo Expressed as GMT
Time frame: Delivery to Day 180
Infants: Percentage of Participants With a Seroresponse to RSV F Vaccine and Placebo
Time frame: Delivery to Day 180
Infant: Immunogenicity of RSV F Vaccine and Placebo Expressed as GMR
Time frame: Day 14 to Day 180
Infants: Mean Length of Participants at Birth
Time frame: At Delivery
Infants: Mean Weight of Participants at Birth
Time frame: At Delivery
Infants: Mean Frontal-occipital Head Circumference of Participants at Birth
Time frame: At Delivery
Infants: Mean APGAR (Appearance, Pulse, Grimace, Activity, Respiration) Score of Participants at Birth
Time frame: At Delivery
Maternal: Number of Participants With Post-immunization Onset of Specific Complications of Third-trimester Pregnancy and Delivery
Time frame: Day 0 to Delivery
Infants: Number of Participants With Developmental Delay
Time frame: Day 364 after delivery
Maternal: Immunogenicity of Anti-RSV F IgG and Placebo Expressed as GMEU (Geometric Mean ELISA Units/mL)
Time frame: Pre-dose to Delivery +180 days
Maternal: Immunogenicity of RSV F Vaccine and Placebo Expressed as GMC (Geometric Mean Concentration)
Time frame: Pre-dose to Delivery +180 days
Maternal: Immunogenicity of RSV F Vaccine and Placebo Expressed as GMT (Geometric Mean Titers)
Time frame: Pre-dose to Delivery +180 days
Maternal: Immunogenicity of RSV F Vaccine and Placebo Expressed as GMTs
Time frame: Pre-dose to Delivery +180 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32726529Madhi SA, Polack FP, Piedra PA, Munoz FM, Trenholme AA, Simoes EAF, Swamy GK, Agrawal S, Ahmed K, August A, Baqui AH, Calvert A, Chen J, Cho I, Cotton MF, Cutland CL, Englund JA, Fix A, Gonik B, Hammitt L, Heath PT, de Jesus JN, Jones CE, Khalil A, Kimberlin DW, Libster R, Llapur CJ, Lucero M, Perez Marc G, Marshall HS, Masenya MS, Martinon-Torres F, Meece JK, Nolan TM, Osman A, Perrett KP, Plested JS, Richmond PC, Snape MD, Shakib JH, Shinde V, Stoney T, Thomas DN, Tita AT, Varner MW, Vatish M, Vrbicky K, Wen J, Zaman K, Zar HJ, Glenn GM, Fries LF; Prepare Study Group. Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants. N Engl J Med. 2020 Jul 30;383(5):426-439. doi: 10.1056/NEJMoa1908380.
- Novavax, IncLink provided by the sponsor.
Related trials for Respiratory Syncytial Virus Infections
RecruitingPhase 3
Study to Learn About a Respiratory Syncytial Virus Vaccine in Children at High Risk of RSV Disease
Respiratory Syncytial Virus (RSV)
Active, not recruitingPhase 3
A Study on the Immune Response and Safety of Vaccine Against Respiratory Syncytial Virus Given to Chinese Adults 18 to 59 Years of Age at Increased Risk of Respiratory Syncytial Virus Disease
Respiratory Syncytial Virus Infections
Active, not recruitingPhase 1
A Phase 1 Study to Evaluate JCXH-108, an mRNA-based Vaccine Against RSV
Respiratory Syncytial Virus (RSV), Infectious Disease
RecruitingPhase 2
Immunogenicity of RSVPreF3 Vaccine in Immunocompromised Persons
Respiratory Syncytial Virus (RSV)
RecruitingObservational study
TARSILA Real-World Evidence Study
Respiratory Syncytial Virus (RSV), Maternal Immunization
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Development study director
Novavax Inc
88 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing RSV F vaccine with adjuvant and Formulation buffer in people with Respiratory Syncytial Virus Infections, run by Novavax at 88 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 88 sites in United States, South Africa, Argentina, Australia, New Zealand and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Infants: Percentages of Participants With Medically Significant RSV LRTI With Either Hypoxemia (SpO2 <95% at Sea Level or <92% at Altitudes >1800 Meters) or Tachypnea (time frame: Delivery to 180 days after delivery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02624947, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2025.