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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02624947
• Date of registration: 04/12/2015
• Prospective Registration: No
• Primary sponsor: Novavax
• Public title: A Study to Determine the Safety and Efficacy of the RSV F Vaccine to Protect Infants Via Maternal Immunization
• Scientific title: A Phase 3, Randomized, Observer-Blind, Placebo-Controlled 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
• Date of first enrolment: December 2015
• Target sample size: 4636
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02624947
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Bangladesh, Chile, Italy, Mexico, New Zealand, Philippines, South Africa, Spain, United Kingdom, United States

Contacts

• Name: D Nigel Thomas, PhD
• Affiliation: Novavax Inc

Key inclusion & exclusion criteria

Inclusion Criteria:

1. =18 and =40 years-of-age

2. 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 should use the earliest ultrasound data
available to establish the study-specific gestational age dating):

1. 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 estable 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.

2. 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.

3. 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.

4. 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.

3. Documentation of a second or third (between 18 0/7 weeks and prior to randomization)
trimester ultrasound with no major fetal anomalies identified.

4. 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.

5. 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.

6. Able and willing to provide written informed consent for themselves and infant.

Exclusion Criteria:

1. 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.

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 (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 immunodeficien


Age minimum: 18 Years
Age maximum: 40 Years
Gender: Female

Health Condition(s) or Problem(s) studied

Respiratory Syncytial Virus Infections

Intervention(s)

Biological: RSV F vaccine with adjuvant

Biological: Formulation buffer

Primary Outcome(s)

Incidence of medically significant RSV LRTI with either hypoxemia (SpO2 <95% at sea level or <92% at altitudes >1800 meters) or tachypnea in infants through 90 days of life [Time Frame: Delivery to 90 days after delivery]

Secondary Outcome(s)

Counts and percentages of maternal subjects 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]

Palivizumab-competitive antibody (PCA) expressed as ug/mL as detected in a competitive ELISA [Time Frame: Day 0 to 180 days after delivery]

RSV F protein antibody expressed as ELISA Units [Time Frame: Day 0 to 180 days after delivery]

Counts and percentages of maternal subjects with post-immunization onset of specific complications of third-trimester pregnancy and delivery [Time Frame: Day 0 to Delivery]

Counts and percentages of subjects with Caesarean, vaginal, or instrument assisted vaginal modes of delivery [Time Frame: Delivery]

Incidence of RSV LRTI with hospitalization in infants through 90 days of life [Time Frame: Delivery to 90 days after delivery]

Counts and percentages of infants with developmental delay [Time Frame: Day 180 to Day 364 after delivery]

Neutralizing antibody titer to at least one RSV/A and one RSV/B virus strain [Time Frame: Delivery to 90 days after delivery]

Counts and percentages of term, healthy infants , APGAR scores, length, birth weight, frontal-occipital head circumference (FOC), and physical examination [Time Frame: Delivery]

Counts and percentages of infants with adverse events and serious adverse events during the neonatal period and through the first year of life [Time Frame: Delivery to 364 days after delivery]

Counts and percentages of maternal subjects with solicited injection site and systemic reactogenicity within seven days of vaccination [Time Frame: Day 0 to Day 7]

Clinical safety laboratory assessments of select serum chemistry and hematology parameters [Time Frame: Day 0 to Delivery]

Incidence of 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 in infants through 90 days of life [Time Frame: Delivery to 90 days after delivery]

Secondary ID(s)

RSV-M-301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Bill and Melinda Gates Foundation