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

Sponsor
Novavax (Industry)
Overall Status
Completed
CT.gov ID
NCT02624947
Collaborator
Bill and Melinda Gates Foundation (Other)
4,636
Enrollment
88
Locations
2
Arms
43
Duration (Months)
52.7
Patients Per Site
1.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: RSV F vaccine with adjuvant
  • Biological: Formulation buffer
 Phase 3

Detailed Description

This is a randomized, observer-blind, placebo-controlled trial enrolling third-trimester pregnant women in the Northern and Southern hemispheres, for up to four consecutive RSV seasons in each hemisphere. The trial will enroll 4636 third-trimester pregnant subjects. Women in the third trimester of a singleton uncomplicated pregnancy and 18 to 40 years of age (inclusive) will be enrolled and randomized in a 1:1 ratio into one of two treatment groups, active or placebo, over approximately the three months prior to peak RSV season. After the first global season of enrollment, the randomization scheme will be changed to a 2:1 (active/placebo) ratio to enable more efficient accrual of the safety database.

All maternal subjects will receive a single intramuscular (IM) injection on Day 0 with the assigned test article, the RSV F vaccine or placebo. Study participation for maternal subjects will span approximately nine (9) months from the first dose, ending six (6) months post-delivery. Study follow-up for infant subjects who are consented will span approximately one (1) year post-delivery.

Study Design

Study Type:
Interventional
Actual Enrollment :
4636 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official 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
Study Start Date :
Dec 1, 2015
Actual Primary Completion Date :
Mar 1, 2019
Actual Study Completion Date :
Jul 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Treatment Group A

Formulation buffer (0.5mL injection)

Biological: Formulation buffer
Active Comparator: Treatment Group

RSV F vaccine with adjuvant (0.5mL injection)

Biological: RSV F vaccine with adjuvant

Outcome Measures

Primary Outcome Measures

  1. 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 [Delivery to 90 days after delivery]

Secondary Outcome Measures

  1. 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 [Delivery to 90 days after delivery]

  2. Incidence of RSV LRTI with hospitalization in infants through 90 days of life [Delivery to 90 days after delivery]

  3. RSV F protein antibody expressed as ELISA Units [Day 0 to 180 days after delivery]

    Geometric Mean Concentrations as EU (GMEU) Geometric Mean Ratio (GMFR) Seroresponse Rate (SRR)

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

    Geometric Mean Concentrations as EU (GMEU) Geometric Mean Fold Rise (GMFR)

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

    Geometric Mean Titer (GMT) Geometric Mean Ratio (GMR)

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

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

  8. Counts and percentages of infants with developmental delay [Day 180 to Day 364 after delivery]

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

  10. 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) [Delivery to 180 days after delivery]

  11. Clinical safety laboratory assessments of select serum chemistry and hematology parameters [Day 0 to Delivery]

  12. Counts and percentages of subjects with Caesarean, vaginal, or instrument assisted vaginal modes of delivery [Delivery]

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

Other Outcome Measures

  1. Incidence of RSV LRTI resulting in death in infants through 90 days of life [Delivery to 90 days after delivery]

  2. Incidence of RSV LRTI (all severities) in infants through 90 days of life [Delivery to 90 days after delivery]

  3. Incidence of healthcare interventions associated with wheezing over the first year of life [Delivery to 364 days after delivery]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 40 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
Yes
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.

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

  6. 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.

  1. 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.

  2. 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.

  1. 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.

  2. 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.

  3. Receipt of any licensed vaccine (e.g., Tdap, inactivated influenza vaccine) within 14 days of study vaccination.

  4. Received any RSV vaccine at any time.

  5. Body mass index (BMI) of ≥40, at the time of the screening visit.

  6. Hemoglobinopathy (even if asymptomatic) or blood dyscrasias.

  7. Hepatic or renal dysfunction.

  8. Established diagnosis of seizure disorder, regardless of therapy.

  9. Known, active auto-immune disease or immunodeficiency syndrome.

  10. 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.

  11. History of major gynecologic or major abdominal surgery, including bariatric surgery (previous Caesarean section is not an exclusion).

  12. 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.

  13. Primary genital Herpes simplex virus (HSV) infection during the current pregnancy.

  14. 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.

  15. Documentation that the current pregnancy results from in vitro fertilization (IVF).

  16. Documentation that the current pregnancy results from rape or incest.

  17. Documentation that the infant will be a ward of the state or be released for adoption.

  18. 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).

  19. Red blood cell allo-immunization.

  20. Prior stillbirth or neonatal death, or multiple (≥3) spontaneous abortions.

  21. Prior preterm delivery ≤34 weeks gestation or having ongoing intervention (medical/surgical) in current pregnancy to prevent preterm birth.

  22. Greater than five (5) prior deliveries.

  23. Previous infant with a known genetic disorder or major congenital anomaly.

  24. 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.

  25. 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.

  26. 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).

  27. 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.

  28. 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).

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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site US115 Birmingham Alabama United States 35233
2 Research Site US035 Cullman Alabama United States 35058
3 Research Site US130 Fort Defiance Arizona United States 86504
4 Research Site US123 Phoenix Arizona United States 85004
5 Research Site US103 Tucson Arizona United States 85712
6 Research Site US129 Whiteriver Arizona United States 85941
7 Research Site US092 Colton California United States 92324
8 Research Site US114 Huntington Park California United States 90255
9 Research Site US127 Los Angeles California United States 90057
10 Research Site US091 Madera California United States 93637
11 Research Site US093 Riverside California United States 94201
12 Research Site US134 Aurora Colorado United States 80045
13 Research Site US036 Denver Colorado United States 80204
14 Research Site US040 Washington District of Columbia United States 20010
15 Research Site US037 Blackfoot Idaho United States 83221
16 Research Site US119 Idaho Falls Idaho United States 83404
17 Research Site US032 Nampa Idaho United States 83687
18 Research Site US095 Chicago Illinois United States 60611
19 Research Site US090 West Des Moines Iowa United States 50266
20 Research Site US038 Augusta Kansas United States 67010
21 Research Site US031 Hutchinson Kansas United States 67502
22 Research Site US096 Louisville Kentucky United States 40202
23 Research Site US126 Alexandria Louisiana United States 71301
24 Research Site US039 Metairie Louisiana United States 70006
25 Research Site US101 Detroit Michigan United States 48235
26 Research Site US098 Biloxi Mississippi United States 39531
27 Research Site US102 Lincoln Nebraska United States 68516
28 Research Site US025 Norfolk Nebraska United States 68701
29 Research Site US088 Neptune New Jersey United States 07753
30 Research Site US131 Gallup New Mexico United States 87301
31 Research Site US087 Johnson City New York United States 13790
32 Research Site US086 Syracuse New York United States 13210
33 Research Site US020 Durham North Carolina United States 27710
34 Research Site US097 Fort Bragg North Carolina United States 28310
35 Research Site US089 Englewood Ohio United States 45322
36 Research Site US021 Pittsburgh Pennsylvania United States 15213
37 Research Site US116 Beaumont Texas United States 77702
38 Research Site US083 Fort Worth Texas United States 77555
39 Research Site US043 Galveston Texas United States 77555
40 Research Site US019 Houston Texas United States 77030
41 Research Site US128 Houston Texas United States 77036
42 Research Site US125 Lampasas Texas United States 76550
43 Research Site US094 Longview Texas United States 75605
44 Research Site US042 San Antonio Texas United States 78229
45 Research Site US121 Salt Lake City Utah United States 84107
46 Research Site US008 Salt Lake City Utah United States 84124
47 Research Site US099 Salt Lake City Utah United States 84132
48 Research Site US100 Richmond Virginia United States 23220
49 Research Site US041 Seattle Washington United States 98105
50 Research Site AR002 Buenos Aires Argentina C1426BOR
51 Research Site AR006 Cordoba Argentina 5000
52 Research Site AR011 Mendoza Argentina 5500
53 Research Site AR008 Salta Argentina 4400
54 Research Site AR003 Tucuman Argentina 4000
55 Research Site AU010 Brisbane Queensland Australia 4101
56 Research Site AU007 Adelaide South Australia Australia 5006
57 Research Site AU011 Clayton Victoria Australia 3148
58 Research Site AU008 Melbourne Victoria Australia 3010
59 Research Site AU009 Perth Western Australia Australia 6008
60 Research Site BD001 Sylhet Sylhet Division Bangladesh 3100
61 Research Site CL001 Santiago Region Metropolitana (RM) Chile 8360160
62 Research Site CL003 Concepcion VIII Region Chile 4070038
63 Research Site CL002 Osorno X Region Chile 5311523
64 Research Site MX001 Monterrey Nuevo Leon Mexico 64460
65 Research Site NZ003 Grafton Auckland New Zealand 1010
66 Research Site NZ001 Papatoetoe Aukland New Zealand 2025
67 Research Site NZ002 Christchurch New Zealand 8140
68 Research Site NZ004 Wellington New Zealand 6021
69 Research Site PH001 Alabang Manila Philippines 1781
70 Research Site PH002 Muntinlupa Metro Manila Philippines 1781
71 Research Site ZA004 Parow Cape Town South Africa 7505
72 Research Site ZA003 Hillbrow Johannesburg South Africa 2001
73 Research Site ZA007 Thabazimbi Limpopo Providence South Africa 0380
74 Research Site ZA010 Bellville Western Cape South Africa 7553
75 Research Site ZA009 Paarl Western Cape South Africa 7646
76 Research Site ZA011 Worcester Western Cape South Africa 6850
77 Research Site ZA006 Benoni South Africa 1500
78 Research Site ZA008 Bloemfontein South Africa 9301
79 Research Site ZA002 Soshanguve South Africa 0152
80 Research Site ZA001 Soweto South Africa 2013
81 Research Site ES002 Barcelona Spain 08035
82 Research Site ES003 Madrid Spain 28046
83 Research Site ES004 Santiago de Compostela Spain 15706
84 Research Site ES001 Sevilla Spain 41012
85 Research Site UK004 Bristol United Kingdom BS2 8EG
86 Research Site UK001 London United Kingdom SW17 0RE
87 Research Site UK002 Oxford United Kingdom OX3 7LE
88 Research Site UK003 Southampton United Kingdom SO16 6YD

Sponsors and Collaborators

  • Novavax
  • Bill and Melinda Gates Foundation

Investigators

  • Study Director: D Nigel Thomas, PhD, Novavax Inc

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Novavax
ClinicalTrials.gov Identifier:
NCT02624947
Other Study ID Numbers:
  • RSV-M-301
First Posted:
Dec 9, 2015
Last Update Posted:
Apr 14, 2020
Last Verified:
Aug 1, 2019
Keywords provided by Novavax
RSV
Additional relevant MeSH terms:
Respiratory Syncytial Virus Infections

Study Results

No Results Posted as of Apr 14, 2020