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Evaluating the Infectivity, Safety and Immunogenicity of Respiratory Syncytial Virus Vaccines, RSV 6120/∆NS1 and RSV 6120/F1/G2/∆NS1, in RSV-Seropositive Children and RSV-Seronegative Infants and Children

Phase 1
Completed
Conditions
RSV Infection
Interventions
Registration Number
NCT03596801
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

The purpose of this study is to evaluate the infectivity, safety, and immunogenicity of a single dose of recombinant, live-attenuated respiratory syncytial virus (RSV) vaccines (RSV 6120/∆NS1 or RSV 6120/F1/G2/∆NS1) in RSV-seropositive children 12 to 59 months of age and RSV-seronegative infants and children 6 to 24 months of age.

Detailed Description

This study will evaluate the infectivity, safety, and immunogenicity of a single dose of recombinant, live-attenuated respiratory syncytial virus (RSV) vaccines (RSV 6120/∆NS1 or RSV 6120/F1/G2/∆NS1) in RSV-seropositive children 12 to 59 months of age and RSV-seronegative infants and children 6 to 24 months of age.

The vaccines will be evaluated in a stepwise fashion beginning with RSV-seropositive children (Group 1) and proceeding sequentially in RSV-seronegative infants and children (Group 2). In each group, participants will be randomly assigned to receive a single dose of RSV 6120/∆NS1, RSV 6120/F1/G2/∆NS1, or placebo at Day 0.

Participants will be enrolled in the study between April 1 and October 31, outside of the RSV season. Group 1 participants will be followed for 28 days after inoculation, and Group 2 participants will remain on the study until they complete the post-RSV season visit between April 1 and April 30 in the calendar year following enrollment. The expected duration of the initial study is 28 days for Group 1 participants and between 6 and 13 months for Group 2 participants, depending upon time of enrollment.

Study visits for all participants may include clinical assessments, blood collection, and nasal washes. Additionally, participants' parents or guardians will be contacted by study staff at various times during the study to monitor participants' health.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 2: RSV 6120/∆NS1 VaccineRSV 6120/∆NS1Healthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of 10\^5.0 PFUs of RSV 6120/∆NS1 vaccine at Day 0.
Group 2: RSV 6120/F1/G2/∆NS1RSV 6120/F1/G2/∆NS1Healthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of 10\^5.0 PFUs of RSV 6120/F1/G2/∆NS1 vaccine at Day 0.
Group 2: PlaceboPlaceboHealthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of placebo at Day 0.
Group 1: RSV 6120/∆NS1 VaccineRSV 6120/∆NS1Healthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of 10\^6.0 plaque-forming units (PFUs) of RSV 6120/∆NS1 vaccine at Day 0.
Group 1: RSV 6120/F1/G2/∆NS1 VaccineRSV 6120/F1/G2/∆NS1Healthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of 10\^5.8 PFUs of RSV 6120/F1/G2/∆NS1 vaccine at Day 0.
Group 1: PlaceboPlaceboHealthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of placebo at Day 0.
Primary Outcome Measures
NameTimeMethod
Grades of study product-related solicited adverse events (AEs) (RSV-seropositive participants)Measured through Day 10

Graded using the protocol-defined grading system

Duration of virus shedding in nasal washes (RSV-seronegative participants)Measured through Day 28

As determined by a) culture and b) rRT-PCR

Grades of study product-related solicited AEs (RSV-seronegative participants)Measured through Day 28

Graded using the protocol-defined grading system

Grades of study product-related serious adverse events (SAEs) (RSV-seropositive participants)Measured through Day 28

Graded using the protocol-defined grading system

Frequency of infection with RSV (RSV-seropositive participants)Measured through Day 28

Defined as 1) vaccine virus identified in nasal wash (a binary outcome based on nasal washes done throughout the study period; Day 0 nasal wash will be counted as baseline) or 2) a greater than or equal to 4-fold rise in serum RSV neutralizing antibody titer or serum RSV F (IgG) titer

Duration of virus shedding in nasal washes (RSV-seropositive participants)Measured through Day 10

As determined by a) culture and b) reverse transcription polymerase chain reaction (rRT-PCR)

Frequency of a greater than or equal to 4-fold rise in RSV-neutralizing antibody titer (RSV-seropositive participants)Measured through Day 28

Based on laboratory evaluations

Frequency of a greater than or equal to 4-fold rise in RSV-neutralizing antibody titer (RSV-seronegative participants)Measured through Day 56

Based on laboratory evaluations

Frequency of a greater than or equal to 4-fold rise in immunoglobulin G (IgG) antibody responses to RSV F glycoprotein (RSV-seropositive participants)Measured through Day 28

As determined by ELISA

Grades of study product-related unsolicited AEs (RSV-seropositive participants)Measured through Day 10

Graded using the protocol-defined grading system

Grades of study product-related unsolicited AEs (RSV-seronegative participants)Measured through Day 28

Graded using the protocol-defined grading system

Grades of study product-related SAEs (RSV-seronegative participants)Measured through Day 56

Graded using the protocol-defined grading system

Peak titer of vaccine virus shed (RSV-seropositive participants)Measured through Day 10

Based on laboratory evaluations

Peak titer of vaccine virus shed (RSV-seronegative participants)Measured through Day 28

Based on laboratory evaluations

Frequency of infection with RSV (RSV-seronegative participants)Measured through Day 56

Defined as 1) vaccine virus identified in nasal wash (a binary outcome based on nasal washes done throughout the study period; Day 0 nasal wash will be counted as baseline) or 2) a greater than or equal to 4-fold rise in serum RSV neutralizing antibody titer or serum RSV F (IgG) titer

Frequency of a greater than or equal to 4-fold rise in IgG antibody responses to RSV F glycoprotein (RSV-seronegative participants)Measured through Day 56

As determined by ELISA

Secondary Outcome Measures
NameTimeMethod
Frequency of symptomatic, medically attended respiratory and febrile illness in the RSV-seronegative (group 2) vaccine and placebo recipients who experience natural infection with wt RSV during the RSV seasonMeasured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study

Based on laboratory evaluations

Severity of symptomatic, medically attended respiratory and febrile illness in the RSV-seronegative (group 2) vaccine and placebo recipients who experience natural infection with wt RSV during the RSV seasonMeasured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study

Based on laboratory evaluations

Frequency of antibody responses in the RSV-seronegative vaccine and placebo recipients who experience natural infection with wt RSV during the RSV seasonMeasured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study

Based on laboratory evaluations

Measurement of mucosal antibody titers to vaccineMeasured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study

Assessed in nasal wash or nasosorption samples

Trial Locations

Locations (1)

Johns Hopkins University Center for Immunization Research

🇺🇸

Baltimore, Maryland, United States

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