A Study to Determine the Safety and Efficacy of the RSV F Vaccine to Protect Infants Via Maternal Immunization

NCT02624947 | Completed Phase 3 Results DMC

• 1 other identifier: RSV-M-301
• Study Type: interventional
• Target: 4,636
• Locations: 11 countries
• Sites: 88

Brief 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 in infants.

Conditions

Respiratory Syncytial Virus Infections

Keywords

RSV

Outcome Measures

Primary Outcomes (1)

• 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).

  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

  Delivery to 180 days after delivery

• Infants: Percentages of Participants With RSV LRTI With Hospitalization From Delivery

  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

  Delivery to 364 days after delivery

• Infants: Number of Participants With Potential Developmental Delay

  Day 180 after delivery

• Maternal: Number of Participants With Solicited Injection Site and Systemic Reactogenicity

  Day 0 to Day 7

Study Arms (2)

Treatment Group A

PLACEBO COMPARATOR

Formulation buffer (0.5mL injection)

Biological: Formulation buffer

Treatment Group

ACTIVE COMPARATOR

RSV F vaccine with adjuvant (0.5mL injection)

Biological: RSV F vaccine with adjuvant

Interventions

RSV F vaccine with adjuvant BIOLOGICAL

Treatment Group

Formulation buffer BIOLOGICAL

Treatment Group A

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• ≥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.
• 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).
• 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.

You may not qualify if:

• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Novavax: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (88)

Research Site US115

Birmingham, Alabama, 35233, United States

Location

Research Site US035

Cullman, Alabama, 35058, United States

Location

Research Site US130

Fort Defiance, Arizona, 86504, United States

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Research Site US123

Phoenix, Arizona, 85004, United States

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Research Site US103

Tucson, Arizona, 85712, United States

Location

Research Site US129

Whiteriver, Arizona, 85941, United States

Location

Research Site US092

Colton, California, 92324, United States

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Research Site US114

Huntington Park, California, 90255, United States

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Research Site US127

Los Angeles, California, 90057, United States

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Research Site US091

Madera, California, 93637, United States

Location

Research Site US093

Riverside, California, 94201, United States

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Research Site US134

Aurora, Colorado, 80045, United States

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Research Site US036

Denver, Colorado, 80204, United States

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Research Site US040

Washington D.C., District of Columbia, 20010, United States

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Research Site US037

Blackfoot, Idaho, 83221, United States

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Research Site US119

Idaho Falls, Idaho, 83404, United States

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Research Site US032

Nampa, Idaho, 83687, United States

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Research Site US095

Chicago, Illinois, 60611, United States

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Research Site US090

West Des Moines, Iowa, 50266, United States

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Research Site US038

Augusta, Kansas, 67010, United States

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Research Site US031

Hutchinson, Kansas, 67502, United States

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Research Site US096

Louisville, Kentucky, 40202, United States

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Research Site US126

Alexandria, Louisiana, 71301, United States

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Research Site US039

Metairie, Louisiana, 70006, United States

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Research Site US101

Detroit, Michigan, 48235, United States

Location

Research Site US098

Biloxi, Mississippi, 39531, United States

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Research Site US102

Lincoln, Nebraska, 68516, United States

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Research Site US025

Norfolk, Nebraska, 68701, United States

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Research Site US088

Neptune City, New Jersey, 07753, United States

Location

Research Site US131

Gallup, New Mexico, 87301, United States

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Research Site US087

Johnson City, New York, 13790, United States

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Research Site US086

Syracuse, New York, 13210, United States

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Research Site US020

Durham, North Carolina, 27710, United States

Location

Research Site US097

Fort Bragg, North Carolina, 28310, United States

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Research Site US089

Englewood, Ohio, 45322, United States

Location

Research Site US021

Pittsburgh, Pennsylvania, 15213, United States

Location

Research Site US116

Beaumont, Texas, 77702, United States

Location

Research Site US083

Fort Worth, Texas, 77555, United States

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Research Site US043

Galveston, Texas, 77555, United States

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Research Site US019

Houston, Texas, 77030, United States

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Research Site US128

Houston, Texas, 77036, United States

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Research Site US125

Lampasas, Texas, 76550, United States

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Research Site US094

Longview, Texas, 75605, United States

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Research Site US042

San Antonio, Texas, 78229, United States

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Research Site US121

Salt Lake City, Utah, 84107, United States

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Research Site US008

Salt Lake City, Utah, 84124, United States

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Research Site US099

Salt Lake City, Utah, 84132, United States

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Research Site US100

Richmond, Virginia, 23220, United States

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Research Site US041

Seattle, Washington, 98105, United States

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Research Site AR002

Buenos Aires, C1426BOR, Argentina

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Research Site AR006

Córdoba, 5000, Argentina

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Research Site AR011

Mendoza, 5500, Argentina

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Research Site AR008

Salta, 4400, Argentina

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Research Site AR003

San Miguel de Tucumán, 4000, Argentina

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Research Site AU010

Brisbane, Queensland, 4101, Australia

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Research Site AU007

Adelaide, South Australia, 5006, Australia

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Research Site AU011

Clayton, Victoria, 3148, Australia

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Research Site AU008

Melbourne, Victoria, 3010, Australia

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Research Site AU009

Perth, Western Australia, 6008, Australia

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Research Site BD001

Sylhet, Sylhet Division, 3100, Bangladesh

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Research Site CL002

Osorno, Los Lagos Region, 5311523, Chile

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Research Site CL001

Santiago, Region Metropolitana (RM), 8360160, Chile

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Research Site CL003

Concepción, Región del Biobío, 4070038, Chile

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Research Site MX001

Monterrey, Nuevo León, 64460, Mexico

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Research Site NZ003

Grafton, Auckland, 1010, New Zealand

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Research Site NZ001

Papatoetoe, Aukland, 2025, New Zealand

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Research Site NZ002

Christchurch, 8140, New Zealand

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Research Site NZ004

Wellington, 6021, New Zealand

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Research Site PH001

Alabang, Manila, 1781, Philippines

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Research Site PH002

Muntinlupa, National Capital Region, 1781, Philippines

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Research Site ZA004

Parow, Cape Town, 7505, South Africa

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Research Site ZA003

Hillbrow, Johannesburg, 2001, South Africa

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Research Site ZA007

Thabazimbi, Limpopo Providence, 0380, South Africa

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Research Site ZA010

Bellville, Western Cape, 7553, South Africa

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Research Site ZA009

Paarl, Western Cape, 7646, South Africa

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Research Site ZA011

Worcester, Western Cape, 6850, South Africa

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Research Site ZA006

Benoni, 1500, South Africa

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Research Site ZA008

Bloemfontein, 9301, South Africa

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Research Site ZA002

Soshanguve, 0152, South Africa

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Research Site ZA001

Soweto, 2013, South Africa

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Research Site ES002

Barcelona, 08035, Spain

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Research Site ES003

Madrid, 28046, Spain

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Research Site ES004

Santiago de Compostela, 15706, Spain

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Research Site ES001

Seville, 41012, Spain

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Research Site UK004

Bristol, BS2 8EG, United Kingdom

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Research Site UK001

London, SW17 0RE, United Kingdom

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Research Site UK002

Oxford, OX3 7LE, United Kingdom

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Research Site UK003

Southampton, SO16 6YD, United Kingdom

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Related Publications (1)

• 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.

  PMID: 32726529 DERIVED

Related Links

• Novavax, Inc

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Interventions

Adjuvants, Pharmaceutic

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Results Point of Contact

• Title: Novavax Customer Service Center
• Organization: Novavax Inc

Clinicaltrials@novavax.com

1-844-Novavax (668-2829)

Study Officials

• Clinical Development

  Novavax Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2015
• First Posted: December 9, 2015
• Study Start: December 1, 2015
• Primary Completion: December 28, 2018
• Study Completion: July 12, 2019
• Last Updated: May 6, 2025
• Results First Posted: May 6, 2025

Record last verified: 2025-04

Locations

AR (5); ZA (10); ES (4); ME (1); GB (4); US (49); BA (1); NZ (4); CL (3); AU (5); PH (2)