RSV-M-301

Novavax, Inc.

21 Firstfield Road, Gaithersburg, United States, 20878

Erika Trahan, Novavax, Inc. , +1 2402682000, etrahan@novavax.com

Greg Glenn, Novavax, Inc. , +1 2402682000, gglenn@novavax.com

No

No

No

Final

12 Jul 2019

No

Yes

12 Jul 2019

No

To determine the efficacy of maternal immunization with the RSV F vaccine against medically-significant RSV lower respiratory tract infection (LRTI) with EITHER hypoxemia (peripheral oxygen saturation [SpO2] < 95% at sea level or < 92% at altitudes > 1800 meters) OR tachypnea (≥ 70 bpm for infants 0 to 59 days of age or ≥ 60 bpm for infants ≥ 60 days of age) 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.

The protocol (and amendments) were reviewed and approved by regulatory authorities in all countries; the protocol (and amendments) and consent were reviewed and approved by the ethical review committees with jurisdiction for all clinical sites. All maternal subjects gave written informed consent, and consent was obtained for infant subjects in accordance with applicable local regulatory requirements and laws. The study was conducted in accordance with the protocol, the Declaration of Helsinki (and amendments) and the International Conference on Harmonisation (ICH) Guidelines on Good Clinical Practice (GCP). An independent Data and Safety Monitoring Board monitored subject safety in a regularly scheduled and completely unblinded manner throughout active enrollment.

03 Dec 2015

No

Yes

United States: 1080

South Africa: 2419

New Zealand: 236

Australia: 113

Chile: 39

Argentina: 247

Mexico: 11

Philippines: 264

Bangladesh: 147

Spain: 38

United Kingdom: 32

4626

70

0

0

0

0

0

0

4626

0

0

Main study (overall period)

Randomised - controlled

Yes

Placebo

Solution for injection in administration system

Intramuscular use

One 0.5 mL dose of placebo (22 mM sodium phosphate, pH 6.2, with 150 mM NaCl, 1.0% histidine, and 0.03% PS-80) administered intramuscularly

Adjuvanted RSV F Vaccine

Suspension for injection in pre-filled syringe

Intramuscular use

0ne 0.5 mL dose of adjuvanted RSV F Vaccine (120 μg RSV F protein with 0.4 mg aluminum as the phosphate salt) administered intramuscularly

Maternal participants - placebo

Maternal participants - RSV F Vaccine

Per-protocol efficacy infant participants

All infant subjects who: a) are ≥ 37 weeks gestational age at birth, b) are born to maternal subjects who received a study injection as randomized and ≥ 2 weeks prior to delivery, c) have not received prophylactic treatment with palivizumab between birth and Day 180 after delivery, d) have at least one documented post-partum contact during which active and/or passive surveillance activities for RSV-suspect illness can occur, and e) have no major protocol deviations affecting the primary efficacy outcomes as determined and documented by Novavax prior to database lock and unblinding.

Infant safety population - placebo

All infants born live to maternal subjects who received placebo

Infant safety population - RSV F Vaccine

All infants born live to maternal subjects who received RSV F Vaccine

Maternal participants - placebo

Maternal participants - RSV F Vaccine

Per-protocol efficacy infant participants

All infant subjects who: a) are ≥ 37 weeks gestational age at birth, b) are born to maternal subjects who received a study injection as randomized and ≥ 2 weeks prior to delivery, c) have not received prophylactic treatment with palivizumab between birth and Day 180 after delivery, d) have at least one documented post-partum contact during which active and/or passive surveillance activities for RSV-suspect illness can occur, and e) have no major protocol deviations affecting the primary efficacy outcomes as determined and documented by Novavax prior to database lock and unblinding.

Infant safety population - placebo

All infants born live to maternal subjects who received placebo

Infant safety population - RSV F Vaccine

All infants born live to maternal subjects who received RSV F Vaccine

Percentages of infants with medically-significant RSV LRTI from delivery through 90, 120, 150, and 180 days of life, defined by: -The presence of RSV infection confirmed by detection of RSV genome by RT PCR on respiratory secretions; AND -At least one of the following: cough, nasal flaring, lower chest wall indrawing, subcostal retractions, stridor, rales, rhonchi, wheezing, crackles/crepitations, or observed apnea; AND -Evidence of medical significance as defined by the presence of: EITHER hypoxemia (peripheral oxygen saturation [SpO2] < 95% at sea level or < 92% at altitudes > 1800 meters) OR Tachypnea (≥ 70 breaths per minute [bpm] in infants 0 to 59 days of age and ≥ 60 bpm in infants ≥ 60 days of age) Data supporting the primary endpoint were obtained exclusively from observations of history and physical examination by trained study site staff, pulse oximetry with the sponsor-supplied device, and RSV detection by molecular diagnostics in the study central laboratory

Primary

From delivery through 90, 120, 150, and 180 days of life

Percentages of infants with RSV LRTI with hospitalization from delivery through 90, 120, 150, and 180 days of life. An event is considered RSV LRTI hospitalization if all parameters outlined below are present during a continuous symptomatic illness episode: - RSV infection as confirmed by detection of the RSV genome by RT-PCR, AND - At least one manifestation of lower respiratory tract infection (LRTI) from among the following: cough, nasal flaring, lower chest wall indrawing, subcostal retractions, stridor, rales, rhonchi, wheezing, crackles/crepitations, or observed apnea, AND - Documented hospitalization Data supporting the secondary endpoints were obtained exclusively from observations of history and physical examination by trained study site staff, pulse oximetry with the sponsor-supplied device, and RSV detection by molecular diagnostics in the study central laboratory

Secondary

Delivery through 90, 120, 150, and 180 days of life

Percentages of infants with RSV LRTI with EITHER severe hypoxemia (SpO2 < 92% at sea level or < 87% at altitudes > 1800 meters) OR the documented use of oxygen by high flow nasal cannula OR a requirement for continuous positive airway pressure OR bilevel positive airway pressure OR Bubble CPAP OR bag-mask ventilation OR intubation with subsequent mechanical ventilation OR extracorporeal membrane oxygenation. An event was considered RSV LRTI with severe hypoxemia if specific parameters were present during a continuous symptomatic illness episode. Data supporting the secondary endpoints were obtained exclusively from observations of history and physical examination by trained study site staff, pulse oximetry with the sponsor-supplied device, and RSV detection by molecular diagnostics in the study central laboratory

Secondary

Delivery through 90, 120, 150, and 180 days of life

Percentages of infants with medically-significant RSV LRTI from delivery through 90, 120, 150, and 180 days of life as defined for the primary endpoint, with the exception that evidence of RSV infection, LRTI, hypoxemia, and/or tachypnea may be based on either or both of the observations of the clinical site staff using sponsor-supplied devices and diagnostic tests OR review and abstraction of medical records for infants undergoing hospitalization for a respiratory serious adverse event.

Other pre-specified

Delivery through 90, 120, 150 and 180 days of life

Percentages of infants with RSV LRTI with hospitalization from delivery through 90, 120, 150, and 180 days of life, defined as for the secondary endpoint, with the exception that evidence of RSV infection and LRTI may be based on either or both of the observations of the clinical site staff using sponsor-supplied devices and diagnostic tests OR review and abstraction of medical records for infants undergoing hospitalization for a respiratory serious adverse event.

Other pre-specified

Delivery through 90, 120, 150 and 180 days of life

Percentages of infants with RSV LRTI with EITHER severe hypoxemia OR the documented use of oxygen by high flow nasal cannula OR a requirement for continuous positive airway pressure (CPAP) OR bilevel positive airway pressure (BiPAP) OR Bubble CPAP OR bag-mask ventilation OR intubation with subsequent mechanical (or manual) ventilation OR extracorporeal membrane oxygenation (ECMO) from delivery through 90, 120, 150, and 180 days of life, as defined for the corresponding secondary endpoint with the exception that evidence of RSV infection, LRTI, severe hypoxemia, and/or respiratory support may be based on either or both of the observations of the clinical site staff using sponsor-supplied devices and diagnostic tests OR review and abstraction of medical records for infants undergoing hospitalization for a respiratory serious adverse event.

Other pre-specified

Delivery through 90, 120, 150 and 180 days of life

In maternal subjects, solicited AEs were collected for 7 days post-dosing and unsolicited AEs were collected through delivery and 180 days thereafter. In infant subjects, AEs were collected through 364 days of life.

Adverse event collection included solicited adverse events typical of IM vaccine reactogenicity in mothers, all adverse events, medically-attended adverse events, adverse events of special interest concerning pregnancy and the puerperium (which were treated as serious adverse events regardless of fulfillment of the ICH criteria for seriousness), an

16.1

Maternal participants - placebo

Maternal participants - RSV F Vaccine

Infant Safety Population - placebo

Infant Safety Population - RSV F Vaccine