Respiratory syncytial virus (RSV) is the leading viral cause of severe lower respiratory tract disease in infants and young children worldwide. In industrialized countries, nearly all children have been infected with RSV by 2 years of age. Most infected children present with mild upper respiratory tract symptoms, but a subset develops severe lower respiratory tract disease characterized by tachypnea, hyperinflation, crackles, and expiratory wheezing (i.e., bronchiolitis and pneumonia). MedDRA v
Conditions
Interventions
Product Name: Adjuvanted RSV F Vaccine
Pharmaceutical Form: Solution for injection
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use
Sponsors
NOVAVAX, INCORPORATED
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) = 18 and = 40 years-of-age. 2) Singleton pregnancy of 28 to 360/7 weeks gestation on the day of planned vaccination. 3) Documentation of gestational age based on last menstrual period, physical exam, and ultrasound 4) Documentation of a second or third (between 180/7 weeks and prior to randomization) trimester ultrasound with no major fetal anomalies identified. 5) Good general maternal health as demonstrated by: o Medical history (including history of clinically significant adverse reactions to prior vaccines and allergies). o Physical examination including at least vital signs (blood pressure, pulse, respirations, and axillary body 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). o Clinical laboratory parameters that include: o 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 third trimester of pregnancy, specified in the toxicity grading scale (TGS, provided in the Study Operations Manual) and should be referenced to assess for any abnormalities. This testing should be performed by the central laboratory. o 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. 6) 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. 7) Able and willing to provide written informed consent for themselves and infant. 8) Estimated date of delivery (EDD) between approximately six (6) weeks before and approximately four (4) weeks after the historic average date of onset of increased RSV transmission at the clinical site using the best data available. The EDD is to be used as a general guidance for enrollment only; infants delivered outside this interval will not be excluded from analyses on the basis of this criterion. (Please refer to the Study Operations Manual for further guidance.) Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 8618 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Symptomatic cardiac or pulmonary disease requiring chronic drug therapy, including hypertension and asthma. Asthma is exclusionary if the subject is receiving chronic systemic glucocorticoids at any dose or inhaled glucocorticoids at any dose > 500 µg per day of beclamethasone or fluticasone, or > 800 µg per day of budesonide. 2) 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. 3) 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. 4) Receipt of any licensed vaccine (e.g., Tdap, inactivated influenza vaccine) within 14 days of study vaccination. 5) Received any RSV vaccine at any time. 6) Body mass index (BMI) of = 40, at the time of the screening visit. 7) Hemoglobinopathy (including known sickle trait or thalassemias, even if asymptomatic) or blood dyscrasias. 8) Hepatic or renal dysfunction. 9) Established diagnosis of seizure disorder, regardless of therapy. 10) Known, active auto-immune disease or immunodeficiency syndrome. 11) 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. 12) History of major gynecologic or major abdominal surgery, including bariatric surgery (previous Caesarean section is not an exclusion). 13) 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. 14) Primary genital Herpes simplex virus (HSV) infection during the current pregnancy. 15) 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. 16) Documentation that the current pregnancy results from in vitro fertilization (IVF). 17) Documentation that the current pregnancy results from rape or incest. 18) Documentation that the infant will be a ward of the state or be released for adoption. 19) History/presence of deep venous thrombosis or thromboembolism, or the use of anticoagulants during pregnancy (use of low-dose aspirin as prophylaxis [e.g., for the prevention of morbidity and mortality from preeclampsia] is acceptable in dosages consistent with local standards of care). 20) Untreated red blood cell allo-immunization. 21) Prior stillbirth or neonatal death, or multiple (= 3) spontaneous abortions. 22) Prior preterm delivery = 34 weeks gestation or having ongoing intervention (medical/surgical) in current pregnancy to prevent preterm birth. 23) Greater than five (5) prior deliveries. 24) Previous infant with a known genetic disorder or major congenital anomaly. 25) 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. 26) Chronic administration (defined as m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of maternal immunization with the RSV F vaccine against RSV lower respiratory tract infection (LRTI) with hypoxemia (peripheral capillary oxygen saturation [SpO2] 1800 meters) through the first 90 days of life in infants of maternal RSV F vaccinees as compared to placebo recipients. In the event that efficacy is shown through the first 90 days of life, a hierarchical sequence of hypothesis tests will be carried out to examine efficacy at 120, 150, and 180 days of life.;Secondary Objective: To determine the efficacy of maternal immunization with the RSV F vaccine in reducing the incidence of: RSV LRTI with severe hypoxemia (SpO2 1800 meters) or the need for high flow nasal cannula or mechanical ventilatory support, RSV LRTI leading to hospitalization, and resulting in death, through the first 90 days of life in infants of maternal RSV F vaccinees as compared to placebo recipients; to determine the efficacy of maternal immunization with the RSV F vaccine in reducing the incidence of all RSV LRTI through the first 90 days of life in infants of maternal RSV F vaccinees as compared to placebo recipients; to determine the efficacy of maternal immunization with the RSV F vaccine in reducing the incidence of healthcare interventions associated with wheezing through the first year of life in infants of maternal RSV F vaccines as compared to placebo recipients.;Primary end point(s): Incidence of RSV LRTI with hypoxemia (SpO2 1800 meters) in infants through 90 days of life. The primary analysis will consider term infants (= 37 weeks of gestation at delivery) of mothers who received test article = 2 weeks prior to delivery. Analyses at 120, 150, and 180 days of age will be performed dependent on successful outcomes at the prior, shorter intervals.;Timepoint(s) of evaluation of this end point: 90 days of age | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Incidence of RSV LRTI with severe hypoxemia (SpO2 1800 meters) or the need of high flow nasal cannula or mechanical ventilatory support in infants through 90 days of life, • Incidence of RSV LRTI with hospitalization in infants through 90 days of life, • Incidence of RSV LRTI resulting in death in infants through 90 days of life, • Incidence of RSV LRTI (all severities) in infants through 90 days of life. • Incidence of healthcare interventions associated with wheezing through the first year of life. A subgroup analysis for all efficacy endpoints will consider all infants of mothers who received test article < 2 weeks prior to delivery and all infants of mothers who received any test article. For all secondary efficacy endpoints, analyses at 120, 150, and 180 days of age will be performed dependent on successful outcomes at the prior, shorter intervals.;Timepoint(s) of evaluation of this end point: 90 days of age | — |
Countries
Argentina, Australia, Belgium, Chile, France, Germany, Italy, Mexico, Mozambique, Netherlands, New Zealand, Philippines, South Africa, Spain, United Kingdom, United States
Contacts
Public ContactDaphne Papanicolaou
Novavax, Inc.
Outcome results
None listed