A Phase II Randomized, Observer-Blind, Placebo-Controlled, Study to Evaluate the Safety and Immunogenicity of a Respiratory Syncytial Virus (RSV) F Nanoparticle Vaccine With Aluminum, in Healthy Third-trimester Pregnant Women and to Assess the Impact of Maternal Immunization on Infant Safety Through One Year of Life
Overview
- Phase
- Phase 2
- Intervention
- Saline Placebo (0.5mL injection)
- Conditions
- Respiratory Syncytial Virus Infections
- Sponsor
- Novavax
- Enrollment
- 50
- Locations
- 7
- Primary Endpoint
- Growth and development over one year
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and immunogenicity of an RSV-F protein nanoparticle vaccine, with aluminum, in healthy third-trimester pregnant women and to assess the impact of maternal immunization on infant safety through one year of life.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pregnant women must meet all of the following criteria to be eligible to participate:
- •≥18 and ≤40 years-of-age.
- •Singleton pregnancy of 33 to 35 weeks gestation on the day of planned vaccination.
- •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.
- •Clinical laboratory parameters including normal blood urea nitrogen, creatinine, ALT, AST, total bilirubin, alkaline phosphatase (ALP), hemoglobin, white blood count, and platelet count; and serologic exclusion of infection with hepatitis B (HBV) and C (HCV) viruses and HIV (as required). Note that normal ranges for vital signs and clinical laboratory parameters will be based on third trimester values published in Sheffield et al. \[2013\] and/or reference ranges for the third trimester of pregnancy of the central laboratory.
- •Documentation that fulfills one of the following:
- •Detailed (level II) second trimester or later anatomic ultrasound with no significant anatomic or growth abnormalities identified; OR
- •Routine second trimester or later ultrasound with no significant anatomic or growth abnormalities identified, PLUS at least one of the following:
Exclusion Criteria
- •Pregnant women will be excluded if there is historical, physical examination, or laboratory evidence of any of the following criteria:
- •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 beclamethasone or fluticasone, or \>800μg per day of budesonide.
- •Pre-pregnancy body mass index (BMI) of ≥35 or \<18.
- •Hemoglobinopathy (including known sickle trait or thalassemias, even if asymptomatic) or blood dyscrasias.
- •Hepatic or renal dysfunction.
- •Established diagnosis of seizure disorder, regardless of therapy.
- •Auto-immune disease or known immunodeficiency syndrome.
- •Endocrine disorders, including (but not limited to) hyperthyroidism, untreated hypothyroidism, 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.
- •Known HIV, 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.
Arms & Interventions
Treatment Group A
Saline Placebo (0.5mL injection)
Intervention: Saline Placebo (0.5mL injection)
Treatment Group B
RSV F vaccine with adjuvant (0.5mL injection)
Intervention: RSV F vaccine (0.5mL injection)
Outcomes
Primary Outcomes
Growth and development over one year
Time Frame: Birth to Day Day 365
In Infant Subjects
Counts and percentage of subjects with post-immunization onset of specific complications of third-trimester pregnancy and delivery
Time Frame: Day 0 to Day 28 - 42
In Maternal Subjects
Counts and percentage of subjects with solicited injection site and systemic reactogenicity within seven days of vaccination.
Time Frame: Day 0 to Day D+180
In Maternal Subjects
Counts and percentage of subjects with unsolicited (local and systemic) adverse events (AE), unscheduled medically-attended adverse events (MAEs), and serious adverse events (SAEs) through delivery and six (6) months thereafter.
Time Frame: Day 0 to Day D+180
In Maternal Subjects
Clinical safety laboratory assessments of select serum chemistry and hematology parameters through delivery.
Time Frame: Screening to Day 14
In Maternal Subjects
Counts and percentage of term healthy infants appropriate for gestational age.
Time Frame: Day 28 - 42
In Infant subjects
Neonatal SAEs (including congenital anomalies, respiratory failure, fever/infection, and neonatal death or other adverse events/complications that necessitate extended hospitalization).
Time Frame: Birth to Day 365
In Infant Subjects
Counts and proportion of infants with unsolicited adverse events
Time Frame: Birth to Day 365
In Infant Subjects
Counts and proportions of infants with medically-attended RSV lower respiratory tract infection (LRTI), and age of onset of those infections.
Time Frame: Birth to Day 365
In Infant Subjects
Secondary Outcomes
- Immunogenicity as assessed by serum IgG antibody titers specific fro the F-Protein antigen.(Birth to Day 180)
- Serum antibody titers inhibiting binding of labeled palivizumab to RSV F protein.(Birth to Day 180)
- Serum microneutralization (MN) titers against RSV/A and B.previously referenced, but based on GMT.(Birth to Day 180)