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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02624947




Registration number
NCT02624947
Ethics application status
Date submitted
4/12/2015
Date registered
9/12/2015
Date last updated
14/04/2020

Titles & IDs
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
Secondary ID [1] 0 0
RSV-M-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory Syncytial Virus Infections 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - RSV F vaccine with adjuvant
Other interventions - Formulation buffer

Placebo Comparator: Treatment Group A - Formulation buffer (0.5mL injection)

Active Comparator: Treatment Group - RSV F vaccine with adjuvant (0.5mL injection)


Other interventions: RSV F vaccine with adjuvant


Other interventions: Formulation buffer
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Delivery to 90 days after delivery
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Delivery to 90 days after delivery
Secondary outcome [2] 0 0
Incidence of RSV LRTI with hospitalization in infants through 90 days of life
Timepoint [2] 0 0
Delivery to 90 days after delivery
Secondary outcome [3] 0 0
RSV F protein antibody expressed as ELISA Units
Timepoint [3] 0 0
Day 0 to 180 days after delivery
Secondary outcome [4] 0 0
Palivizumab-competitive antibody (PCA) expressed as ug/mL as detected in a competitive ELISA
Timepoint [4] 0 0
Day 0 to 180 days after delivery
Secondary outcome [5] 0 0
Neutralizing antibody titer to at least one RSV/A and one RSV/B virus strain
Timepoint [5] 0 0
Delivery to 90 days after delivery
Secondary outcome [6] 0 0
Counts and percentages of term, healthy infants , APGAR scores, length, birth weight, frontal-occipital head circumference (FOC), and physical examination
Timepoint [6] 0 0
Delivery
Secondary outcome [7] 0 0
Counts and percentages of infants with adverse events and serious adverse events during the neonatal period and through the first year of life
Timepoint [7] 0 0
Delivery to 364 days after delivery
Secondary outcome [8] 0 0
Counts and percentages of infants with developmental delay
Timepoint [8] 0 0
Day 180 to Day 364 after delivery
Secondary outcome [9] 0 0
Counts and percentages of maternal subjects with solicited injection site and systemic reactogenicity within seven days of vaccination
Timepoint [9] 0 0
Day 0 to Day 7
Secondary outcome [10] 0 0
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)
Timepoint [10] 0 0
Delivery to 180 days after delivery
Secondary outcome [11] 0 0
Clinical safety laboratory assessments of select serum chemistry and hematology parameters
Timepoint [11] 0 0
Day 0 to Delivery
Secondary outcome [12] 0 0
Counts and percentages of subjects with Caesarean, vaginal, or instrument assisted vaginal modes of delivery
Timepoint [12] 0 0
Delivery
Secondary outcome [13] 0 0
Counts and percentages of maternal subjects with post-immunization onset of specific complications of third-trimester pregnancy and delivery
Timepoint [13] 0 0
Day 0 to Delivery

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
40 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key 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 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 (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).

20. 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 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.

27. 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).

28. 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.

29. 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).

30. History of a serious adverse reactions (e.g., anaphylaxis) to any prior vaccine.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2019
Sample size
Target
Accrual to date
Final
4636
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Research Site AU010 - Brisbane
Recruitment hospital [2] 0 0
Research Site AU007 - Adelaide
Recruitment hospital [3] 0 0
Research Site AU011 - Clayton
Recruitment hospital [4] 0 0
Research Site AU008 - Melbourne
Recruitment hospital [5] 0 0
Research Site AU009 - Perth
Recruitment postcode(s) [1] 0 0
4101 - Brisbane
Recruitment postcode(s) [2] 0 0
5006 - Adelaide
Recruitment postcode(s) [3] 0 0
3148 - Clayton
Recruitment postcode(s) [4] 0 0
3010 - Melbourne
Recruitment postcode(s) [5] 0 0
6008 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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California
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Colorado
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District of Columbia
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Idaho
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Illinois
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Iowa
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Kansas
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Kentucky
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Louisiana
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Michigan
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Mississippi
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Nebraska
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New Jersey
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New Mexico
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Utah
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Washington
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Argentina
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Buenos Aires
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Cordoba
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Mendoza
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Salta
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Argentina
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Tucuman
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Bangladesh
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Sylhet Division
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Chile
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Chile
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Chile
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Mexico
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Nuevo Leon
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Auckland
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Aukland
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Christchurch
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Wellington
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Philippines
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Manila
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Philippines
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Metro Manila
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Cape Town
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Johannesburg
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South Africa
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Limpopo Providence
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South Africa
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Western Cape
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South Africa
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Benoni
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South Africa
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Bloemfontein
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Soshanguve
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Soweto
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Spain
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Barcelona
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Madrid
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Santiago de Compostela
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Sevilla
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Bristol
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London
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Oxford
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Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novavax
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Bill and Melinda Gates Foundation
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine the efficacy of maternal immunization with the RSV
F vaccine against symptomatic RSV lower respiratory tract infection (LRTI) with hypoxemia
through the first 90 days of life in infants.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02624947
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
D Nigel Thomas, PhD
Address 0 0
Novavax Inc
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
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Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries