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The purpose of this study is to evaluate the infectivity, safety, and immunogenicity of a single dose of a recombinant, live-attenuated respiratory syncytial virus (RSV) vaccine (RSV 6120/∆NS2/1030s) in RSV-seropositive children 12 to 59 months of age and RSV-seronegative infants and children 6 to 24 months of age.
This study will evaluate the infectivity, safety, and immunogenicity of a single dose of a recombinant, live-attenuated RSV vaccine (RSV 6120/∆NS2/1030s) in RSV-seropositive children 12 to 59 months of age and RSV-seronegative infants and children 6 to 24 months of age.
The vaccine will be evaluated in a stepwise fashion beginning in RSV-seropositive children (Group 1), and then in RSV-seronegative infants and children (Group 2). In each group, participants will be randomly assigned to receive a single dose of RSV 6120/∆NS2/1030s vaccine or placebo at study entry (Day 0).
Participants will be enrolled in the study between April 1 and October 31, outside of the RSV season. Group 1 (RSV-seropositive children) will be followed for 28 days. Group 2 (RSV-seronegative infants and children) will remain on study until they complete the post-RSV season visit.
Group 2 participants may participate in an optional second season of RSV surveillance during November to March of the second year following 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1: RSV 6120/∆NS2/1030s Vaccine | Experimental | RSV-seropositive children will receive a single dose of 10^5.7 plaque-forming units (PFUs) of RSV 6120/∆NS2/1030s vaccine at study entry (Day 0). |
|
| Group 1: Placebo | Placebo Comparator | RSV-seropositive children will receive a single dose of placebo at study entry (Day 0). |
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| Group 2: RSV 6120/∆NS2/1030s Vaccine | Experimental | RSV-seronegative infants and children will receive a single dose of 10^5.0 PFUs of RSV 6120/∆NS2/1030s vaccine at study entry (Day 0). |
|
| Group 2: Placebo | Placebo Comparator | RSV-seronegative infants and children will receive a single dose of placebo at study entry (Day 0). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RSV 6120/∆NS2/1030s | Biological | Delivered as nose drops |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Solicited Adverse Events (AEs) by Grade - (RSV-seropositive Participants) | Solicited adverse events include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI) as defined in Appendix IV of the protocol document. The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each solicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 4-life-threatening) following protocol-defined grading system outlined in Table 21 and Table 22 in the protocol document. | Measured through Day 10 |
| Number of Participants With Solicited Adverse Events (AEs) by Grade - (RSV-seronegative Participants) | Solicited adverse events include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI) as defined by Appendix IV in the protocol document . The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each solicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 4-life-threatening) following protocol-defined grading system outlined in Table 21 and Table 22 in the protocol document. | Measured through Day 28 |
| Number of Participants With Unsolicited Adverse Events (AEs) - (RSV-seropositive Participants) | Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented. | Measured through Day 10 |
| Number of Participants With Unsolicited Adverse Events (AEs) - (RSV-seronegative Participants) | Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of RSV-seronegative (Group 2) Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the First RSV Season | As defined as 1) RSV identified in a nasal wash (a binary outcome based on nasal washes done throughout the RSV surveillance period; or 2) a greater than or equal to 4-fold rise in RSV neutralizing antibody titer or Serum IgG RSV F antibody titer from pre- to post-RSV Surveillance season |
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Inclusion Criteria for RSV-Seropositive Children:
Exclusion Criteria for RSV-Seropositive Children:
Born at less than 34 weeks gestation
Maternal history of positive HIV test
Evidence of chronic disease
Known or suspected impairment of immune function
Bone marrow/solid organ transplant recipient
Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities
Suspected or documented developmental disorder, delay, or other developmental problem
Cardiac abnormality requiring treatment
Lung disease or reactive airway disease
More than one episode of wheezing in the first year of life
Wheezing episode or received bronchodilator therapy within the past 12 months
Wheezing episode or received bronchodilator therapy after the age of 12 months
Previous receipt of supplemental oxygen therapy in a home setting
Previous receipt of an investigational RSV vaccine
Previous receipt or planned administration of anti-RSV drug (ribavirin) or RSV antibody product including RSV immune globulin (RSV Ig) or RSV monoclonal antibody (RSV mAb)
Previous receipt of immunoglobulin or any antibody products within the past 6 months
Previous receipt of any other blood products within the past 6 months
Previous anaphylactic reaction
Previous vaccine-associated adverse reaction that was Grade 3 or above
Known hypersensitivity to any vaccine component
Member of a household that contains an infant who is less than 12 months of age at the date of inoculation through the 10th day after inoculation
Member of a household that, at the date of inoculation through the 10th day after inoculation, contains an immunocompromised individual including but not limited to:
Will attend a daycare facility that does not separate children by age and contains an infant who is less than 12 months of age at the date of inoculation through the 10th day after inoculation
Receipt of any of the following prior to enrollment:
Scheduled administration of any of the following after planned inoculation:
Receipt of any of the following medications within 3 days of study enrollment:
Any of the following events at the time of enrollment:
Inclusion Criteria for RSV-Seronegative Infants and Children:
Greater than or equal to 6 months of age and less than 25 months of age at the time of inoculation
Screening and pre-inoculation serum specimens for RSV-neutralizing antibody are obtained no more than 42 days prior to inoculation
Seronegative for RSV antibody, defined as serum RSV-neutralizing antibody titer less than 1:40
In good health based on review of the medical record, history, and physical examination at the time of inoculation
Received routine immunizations appropriate for age based on the ACIP Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger
Growing normally for age as demonstrated on a standard growth chart, AND
Expected to be available for the duration of the study
Parent/guardian is willing and able to provide written informed consent
Exclusion Criteria for RSV-Seronegative Infants and Children:
Born at less than 34 weeks gestation
Born at less than 37 weeks gestation, and at the date of inoculation less than 1 year of age
Maternal history of a positive HIV test
Evidence of chronic disease
Known or suspected infection or impairment of immunological functions
Bone marrow/solid organ transplant recipient
Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities
Suspected or documented developmental disorder, delay, or other developmental problem
Cardiac abnormality requiring treatment
Lung disease or reactive airway disease
More than one episode of wheezing in the first year of life
Wheezing episode or received bronchodilator therapy within the past 12 months
Wheezing episode or received bronchodilator therapy after the age of 12 months
Previous receipt of supplemental oxygen therapy in a home setting
Previous receipt of an investigational RSV vaccine
Previous receipt or planned administration of anti-RSV antibody product including ribavirin, RSV Ig, or RSV mAb
Previous receipt of immunoglobulin or any antibody products within the past 6 months
Previous receipt of any blood products within the past 6 months
Previous anaphylactic reaction
Previous vaccine-associated adverse reaction that was Grade 3 or above
Known hypersensitivity to any study product component
Member of a household that contains an infant who is less than 6 months of age at the date of inoculation through the 28th day after inoculation
Member of a household that, at the date of inoculation through the 28th day after inoculation, contains an immunocompromised individual including but not limited to:
Attends a daycare facility that does not separate children by age and contains an infant less than 6 months of age at the date of inoculation through the 28th day after inoculation
Receipt of any of the following prior to enrollment:
Scheduled administration of any of the following after planned inoculation
Receipt of any of the following medications within 3 days of study enrollment:
Any of the following events at the time of enrollment:
Inclusion Criteria for RSV-Seronegative Children Participating in a Second Season of RSV Surveillance:
Exclusion Criteria for RSV-Seronegative Children Participating in a Second Season of RSV Surveillance:
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| Name | Affiliation | Role |
|---|---|---|
| Ruth A. Karron, MD | Johns Hopkins Bloomberg School of Public Health (JHSPH) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health | Baltimore | Maryland | 21205 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37493269 | Result | Karron RA, Luongo C, Woods S, Oliva J, Collins PL, Buchholz UJ; RSVPed Team. Evaluation of the Live-Attenuated Intranasal Respiratory Syncytial Virus (RSV) Vaccine RSV/6120/DeltaNS2/1030s in RSV-Seronegative Young Children. J Infect Dis. 2024 Feb 14;229(2):346-354. doi: 10.1093/infdis/jiad281. |
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Of the 73 participants that were screened, 45 met eligibility criteria, parent agreed to enroll and were inoculated with study product.
Participants were recruited from pediatric practices and clinics in the greater Baltimore/Washington area based on referral by the primary care provider or the provider's staff; and through mailing IRB-approved documents to children of local pediatric practices and clinics, and to households in local zip codes containing age-appropriate children between September 2017 and September 2019. The first participant was enrolled on 10/13/2017 and the last participant was enrolled on 9/27/2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1: RSV 6120/∆NS2/1030s Vaccine | RSV-seropositive children will receive a single dose of 10^5.7 plaque-forming units (PFUs) of RSV 6120/∆NS2/1030s vaccine at study entry (Day 0). RSV 6120/∆NS2/1030s: Delivered as nose drops |
| FG001 | Group 1: Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 6, 2020 |
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| Placebo | Biological | Delivered as nose drops |
|
| Measured through Day 28 |
| Number of Participants With Serious Adverse Events (SAEs) (RSV-seropositive Participants) | A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that:
| Measured through Day 28 |
| Number of Participants With Serious Adverse Events (SAEs) (RSV-seronegative Participants) | A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that:
| Measured through Day 56 |
| Frequency of Infection With RSV Vaccine Virus (RSV-seropositive Subjects) | As defined as 1) vaccine virus identified in a nasal wash (a binary outcome based on nasal washes done throughout the study period; Day 0 nasal wash will be counted as baseline) and/or 2) a greater than or equal to 4-fold rise in RSV neutralizing antibody titer and/or serum enzyme-linked immunosorbent assay (ELISA) titer to the RSV F protein from study entry to Study Day 28. | Measured through Day 28 |
| Frequency of Infection With RSV Vaccine Virus (RSV-seronegative Subjects) | As defined as 1) vaccine virus identified in a nasal wash (a binary outcome based on nasal washes done throughout the study period; Day 0 nasal wash will be counted as baseline) and/or 2) a greater than or equal to 4-fold rise in RSV neutralizing antibody titer and/or serum enzyme-linked immunosorbent assay (ELISA) titer to the RSV F protein from study entry to Study Day 56. | Measured through Day 56 |
| Peak Titer of Vaccine Virus Shed Measured by Culture (RSV-seropositive Subjects) | This is the mean of the highest value per participant of the titer of vaccine virus shed. It was measured by culture. Only participants who met the definition of infection with vaccine virus were included. | Measured at Days 0, 3, 4, 5, 6, 7 and 10 |
| Peak Titer of Vaccine Virus Shed Measured by Reverse Transcription Polymerase Chain Reaction (RSV-seropositive Subjects) | This is the mean of the highest value per participant of the titer of vaccine virus shed. It was measured by reverse transcription polymerase chain reaction (RT-PCR). Only participants who met the definition of infection with vaccine virus were included. | Measured at Days 0, 3, 4, 5, 6, 7 and 10 |
| Duration of Vaccine Virus Shedding in Nasal Washes (RSV-seropositive Subjects) | As determined by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR) | Measured at Days 0, 3, 4, 5, 6, 7 and 10. Last day positive is reported. |
| Peak Titer of Vaccine Virus Shed by Culture (RSV-seronegative Subjects) | This is the mean of the highest value per participant of the titer of vaccine virus shed. It was measured by culture. Only participants who met the definition of infection with vaccine virus were included. | Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28 |
| Peak Titer of Vaccine Virus Shed by Reverse Transcription Polymerase Chain Reaction (RSV-seronegative Subjects) | This is the mean of the highest value per participant of the titer of vaccine virus shed. It was measured by reverse transcription polymerase chain reaction (RT-PCR). Only participants who met the definition of infection with vaccine virus were included. | Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28 |
| Duration of Vaccine Virus Shedding in Nasal Washes (RSV-seronegative Subjects) | As determined by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR) | Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28. Lat day positive is reported |
| Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein(RSV-seropositive Subjects) | Serum RSV-neutralizing antibody titers were assessed by 60% RSV-plaque reduction neutralization titer (RSV-PRNT) assay and an Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points. | Measured at Day 0 and Day 28 |
| Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein (RSV-seronegative Subjects) | Serum RSV-neutralizing antibody titers were assessed by 60% RSV-plaque reduction neutralization titer (RSV-PRNT) assay and an Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points. | Measured at Day 0 and Day 56 |
| RSV-neutralizing Serum Antibody Titer and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA)(RSV-seropositive Subjects) | Serum RSV-neutralizing antibody titers were assessed by 60% RSV-plaque reduction neutralization titer (RSV-PRNT) assay. Serum antibody titers to RSV F glycoprotein were assessed by ELISA. | Measured at Day 28 |
| RSV-neutralizing Serum Antibody Titers and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA) (RSV-seronegative Subjects) | Serum RSV-neutralizing antibody titers were assessed by 60% RSV-plaque reduction neutralization titer (RSV-PRNT) assay. Serum antibody titers to RSV F glycoprotein were assessed by ELISA. | Measured at Day 56 |
| Measured through participants' last study visit, up to a total of 6 to 13 months after study entry, depending on when participants enrolled in the study. |
| 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 First RSV Season | The number of participants who had RSV-associated, symptomatic, medically attended respiratory and febrile illness (MAARI) among those who had indicators of natural infection with wt RSV were presented. Natural infection with wt RSV during the RSV season surveillance was defined as having either RSV detected in nasal washes collected during illness visits for MAARI events or a > 4-fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events. | Measured through participants' last study visit, up to a total of 6 to 13 months after study entry, depending on when participants enroll in the study. |
| 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 First RSV Season | The number of participants who had RSV-associated, symptomatic, medically attended respiratory and febrile illness (MAARI) among those who had indicators of natural infection with wt RSV were presented. Natural infection with wt RSV during the RSV season surveillance was defined as having either RSV detected in nasal washes collected during illness visits for MAARI events or a > 4-fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events. A participant was only counted once in each MAARI category, and that was in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 4-life-threatening) following protocol-defined grading system outlined in Table 21 and Table 22 in the protocol document.Assessed by protocol-determined grading system | Measured through participants' last study visit, up to a total of 6 to 13 months after study entry, depending on when participants enroll in the study |
| Serum RSV-neutralizing Antibody Titers and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA) in Subjects (RSV-seronegative) Infected With wt RSV During the RSV Surveillance | Antibodies were assessed by RSV-neutralizing Antibody and Enzyme-linked Immunosorbent Assay (ELISA). A response was defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre- and post-RSV Surveillance time points. | Measured pre- RSV Surveillance period (baseline) and post-RSV Surveillance period (4-6 months after the baseline) |
| Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein in RSV-seronegative Subjects (Group 2) Infected With wt RSV During the RSV Surveillance | Serum RSV-neutralizing antibody titers were assessed by 60% RSV-plaque reduction neutralization titer (RSV-PRNT) assay and an Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-RSV surveillance and post-RSV surveillance time points among those who had indicators of natural infection with wt RSV were presented. Natural infection with wt RSV during the RSV season surveillance was defined as having either RSV detected in nasal washes collected during illness visits for MAARI events or a > 4-fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events | Measured pre-RSV Surveillance period (baseline) and post-RSV Surveillance period (4-6 months after the baseline) |
RSV-seropositive children will receive a single dose of placebo at study entry (Day 0). Placebo: Delivered as nose drops |
| FG002 | Group 2: RSV 6120/∆NS2/1030s Vaccine | RSV-seronegative infants and children will receive a single dose of 10^5.0 PFUs of RSV 6120/∆NS2/1030s vaccine at study entry (Day 0). RSV 6120/∆NS2/1030s: Delivered as nose drops |
| FG003 | Group 2: Placebo | RSV-seronegative infants and children will receive a single dose of placebo at study entry (Day 0). Placebo: Delivered as nose drops |
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1: RSV 6120/∆NS2/1030s Vaccine | RSV-seropositive children will receive a single dose of 10^5.7 plaque-forming units (PFUs) of RSV 6120/∆NS2/1030s vaccine at study entry (Day 0). RSV 6120/∆NS2/1030s: Delivered as nose drops |
| BG001 | Group 1: Placebo | RSV-seropositive children will receive a single dose of placebo at study entry (Day 0). Placebo: Delivered as nose drops |
| BG002 | Group 2: RSV 6120/∆NS2/1030s Vaccine | RSV-seronegative infants and children will receive a single dose of 10^5.0 PFUs of RSV 6120/∆NS2/1030s vaccine at study entry (Day 0). RSV 6120/∆NS2/1030s: Delivered as nose drops |
| BG003 | Group 2: Placebo | RSV-seronegative infants and children will receive a single dose of placebo at study entry (Day 0). Placebo: Delivered as nose drops |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Group 1 enrolled children 12-59 months of age. Group 2 enrolled infants and children 6-24 months of age. | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Solicited Adverse Events (AEs) by Grade - (RSV-seropositive Participants) | Solicited adverse events include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI) as defined in Appendix IV of the protocol document. The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each solicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 4-life-threatening) following protocol-defined grading system outlined in Table 21 and Table 22 in the protocol document. | Study participants who received inoculation and were followed on study past Day 0 were included. | Posted | Count of Participants | Participants | Measured through Day 10 |
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| Primary | Number of Participants With Solicited Adverse Events (AEs) by Grade - (RSV-seronegative Participants) | Solicited adverse events include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI) as defined by Appendix IV in the protocol document . The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each solicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 4-life-threatening) following protocol-defined grading system outlined in Table 21 and Table 22 in the protocol document. | Study participants who received inoculation and were followed on study past Day 0 were included. | Posted | Count of Participants | Participants | Measured through Day 28 |
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| Primary | Number of Participants With Unsolicited Adverse Events (AEs) - (RSV-seropositive Participants) | Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented. | Study participants who received inoculation and were followed on study past Day 0 were included. | Posted | Count of Participants | Participants | Measured through Day 10 |
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| Primary | Number of Participants With Unsolicited Adverse Events (AEs) - (RSV-seronegative Participants) | Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented. | Study participants who received inoculation and were followed on study past Day 0 were included. | Posted | Count of Participants | Participants | Measured through Day 28 |
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| Primary | Number of Participants With Serious Adverse Events (SAEs) (RSV-seropositive Participants) | A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that:
| Study participants who received inoculation and were followed on study past Day 0 were included. | Posted | Count of Participants | Participants | Measured through Day 28 |
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| Primary | Number of Participants With Serious Adverse Events (SAEs) (RSV-seronegative Participants) | A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that:
| Study participants who received inoculation and were followed on study pst Day 0 were included. | Posted | Count of Participants | Participants | Measured through Day 56 |
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| Primary | Frequency of Infection With RSV Vaccine Virus (RSV-seropositive Subjects) | As defined as 1) vaccine virus identified in a nasal wash (a binary outcome based on nasal washes done throughout the study period; Day 0 nasal wash will be counted as baseline) and/or 2) a greater than or equal to 4-fold rise in RSV neutralizing antibody titer and/or serum enzyme-linked immunosorbent assay (ELISA) titer to the RSV F protein from study entry to Study Day 28. | Study participants who received inoculation and were followed on study past Day 0 were included. | Posted | Count of Participants | Participants | Measured through Day 28 |
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| Primary | Frequency of Infection With RSV Vaccine Virus (RSV-seronegative Subjects) | As defined as 1) vaccine virus identified in a nasal wash (a binary outcome based on nasal washes done throughout the study period; Day 0 nasal wash will be counted as baseline) and/or 2) a greater than or equal to 4-fold rise in RSV neutralizing antibody titer and/or serum enzyme-linked immunosorbent assay (ELISA) titer to the RSV F protein from study entry to Study Day 56. | Posted | Count of Participants | Participants | Measured through Day 56 |
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| Primary | Peak Titer of Vaccine Virus Shed Measured by Culture (RSV-seropositive Subjects) | This is the mean of the highest value per participant of the titer of vaccine virus shed. It was measured by culture. Only participants who met the definition of infection with vaccine virus were included. | Only participants who met the definition of infection with vaccine virus were included. | Posted | Mean | Standard Deviation | log 10 PFU/mL | Measured at Days 0, 3, 4, 5, 6, 7 and 10 |
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| Primary | Peak Titer of Vaccine Virus Shed Measured by Reverse Transcription Polymerase Chain Reaction (RSV-seropositive Subjects) | This is the mean of the highest value per participant of the titer of vaccine virus shed. It was measured by reverse transcription polymerase chain reaction (RT-PCR). Only participants who met the definition of infection with vaccine virus were included. | Only participants who met the definition of infection with vaccine virus were included. | Posted | Mean | Standard Deviation | log 10 copies/mL | Measured at Days 0, 3, 4, 5, 6, 7 and 10 |
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| Primary | Duration of Vaccine Virus Shedding in Nasal Washes (RSV-seropositive Subjects) | As determined by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR) | Only participants who met the definition of infection with vaccine virus were included. | Posted | Mean | Full Range | Days | Measured at Days 0, 3, 4, 5, 6, 7 and 10. Last day positive is reported. |
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| Primary | Peak Titer of Vaccine Virus Shed by Culture (RSV-seronegative Subjects) | This is the mean of the highest value per participant of the titer of vaccine virus shed. It was measured by culture. Only participants who met the definition of infection with vaccine virus were included. | Only participants who met the definition of infection with vaccine virus were included. | Posted | Mean | Standard Deviation | log 10 PFU/mL | Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28 |
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| Primary | Peak Titer of Vaccine Virus Shed by Reverse Transcription Polymerase Chain Reaction (RSV-seronegative Subjects) | This is the mean of the highest value per participant of the titer of vaccine virus shed. It was measured by reverse transcription polymerase chain reaction (RT-PCR). Only participants who met the definition of infection with vaccine virus were included. | Only participants who met the definition of infection with vaccine virus were included. | Posted | Mean | Standard Deviation | log 10 copies/mL | Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28 |
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| Primary | Duration of Vaccine Virus Shedding in Nasal Washes (RSV-seronegative Subjects) | As determined by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR) | Only participants who met the definition of infection with vaccine virus were included. | Posted | Mean | Full Range | Days | Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28. Lat day positive is reported |
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| Primary | Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein(RSV-seropositive Subjects) | Serum RSV-neutralizing antibody titers were assessed by 60% RSV-plaque reduction neutralization titer (RSV-PRNT) assay and an Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points. | Study participants who received inoculation and were followed on study past Day 0 were included. | Posted | Count of Participants | Participants | Measured at Day 0 and Day 28 |
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| Primary | Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein (RSV-seronegative Subjects) | Serum RSV-neutralizing antibody titers were assessed by 60% RSV-plaque reduction neutralization titer (RSV-PRNT) assay and an Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points. | Study participants who received inoculation and were followed on study past Day 0 were included. | Posted | Count of Participants | Participants | Measured at Day 0 and Day 56 |
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| Primary | RSV-neutralizing Serum Antibody Titer and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA)(RSV-seropositive Subjects) | Serum RSV-neutralizing antibody titers were assessed by 60% RSV-plaque reduction neutralization titer (RSV-PRNT) assay. Serum antibody titers to RSV F glycoprotein were assessed by ELISA. | Study participants who received inoculation and were followed on study past Day 0 were included. | Posted | Mean | Standard Deviation | log 2 titers | Measured at Day 28 |
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| Primary | RSV-neutralizing Serum Antibody Titers and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA) (RSV-seronegative Subjects) | Serum RSV-neutralizing antibody titers were assessed by 60% RSV-plaque reduction neutralization titer (RSV-PRNT) assay. Serum antibody titers to RSV F glycoprotein were assessed by ELISA. | Study participants who received inoculation and were followed on study past Day 0 were included. | Posted | Mean | Standard Deviation | log 2 titers | Measured at Day 56 |
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| Secondary | Number of RSV-seronegative (Group 2) Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the First RSV Season | As defined as 1) RSV identified in a nasal wash (a binary outcome based on nasal washes done throughout the RSV surveillance period; or 2) a greater than or equal to 4-fold rise in RSV neutralizing antibody titer or Serum IgG RSV F antibody titer from pre- to post-RSV Surveillance season | Only participants who had RSV detected in nasal washes or had greater than or equal to 4 fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events were included. Four vaccinees and 2 placebo recipients were excluded due to SARS CoV-2 pandemic and no post-surveillance sample. | Posted | Count of Participants | Participants | Measured through participants' last study visit, up to a total of 6 to 13 months after study entry, depending on when participants enrolled in the study. |
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| Secondary | 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 First RSV Season | The number of participants who had RSV-associated, symptomatic, medically attended respiratory and febrile illness (MAARI) among those who had indicators of natural infection with wt RSV were presented. Natural infection with wt RSV during the RSV season surveillance was defined as having either RSV detected in nasal washes collected during illness visits for MAARI events or a > 4-fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events. | Only participants who had RSV detected in nasal washes or had greater than or equal to 4 fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events were included. Four vaccinees and 2 placebo recipients were excluded due to SARS CoV-2 pandemic and no post-surveillance sample. | Posted | Count of Participants | Participants | Measured through participants' last study visit, up to a total of 6 to 13 months after study entry, depending on when participants enroll in the study. |
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| Secondary | 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 First RSV Season | The number of participants who had RSV-associated, symptomatic, medically attended respiratory and febrile illness (MAARI) among those who had indicators of natural infection with wt RSV were presented. Natural infection with wt RSV during the RSV season surveillance was defined as having either RSV detected in nasal washes collected during illness visits for MAARI events or a > 4-fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events. A participant was only counted once in each MAARI category, and that was in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 4-life-threatening) following protocol-defined grading system outlined in Table 21 and Table 22 in the protocol document.Assessed by protocol-determined grading system | Only participants who had RSV detected in nasal washes or had greater than or equal to 4 fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events were included. Four vaccinees and 2 placebo recipients were excluded due to SARS CoV-2 pandemic and no post-surveillance sample. | Posted | Count of Participants | Participants | Measured through participants' last study visit, up to a total of 6 to 13 months after study entry, depending on when participants enroll in the study |
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| Secondary | Serum RSV-neutralizing Antibody Titers and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA) in Subjects (RSV-seronegative) Infected With wt RSV During the RSV Surveillance | Antibodies were assessed by RSV-neutralizing Antibody and Enzyme-linked Immunosorbent Assay (ELISA). A response was defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre- and post-RSV Surveillance time points. | Only participants who had RSV detected in nasal washes or had greater than or equal to 4 fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events were included. Four vaccinees and 3 placebo recipients were excluded due to SARS CoV-2 pandemic and no post-surveillance sample. | Posted | Mean | Standard Deviation | log 2 titers | Measured pre- RSV Surveillance period (baseline) and post-RSV Surveillance period (4-6 months after the baseline) |
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| Secondary | Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein in RSV-seronegative Subjects (Group 2) Infected With wt RSV During the RSV Surveillance | Serum RSV-neutralizing antibody titers were assessed by 60% RSV-plaque reduction neutralization titer (RSV-PRNT) assay and an Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-RSV surveillance and post-RSV surveillance time points among those who had indicators of natural infection with wt RSV were presented. Natural infection with wt RSV during the RSV season surveillance was defined as having either RSV detected in nasal washes collected during illness visits for MAARI events or a > 4-fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events | Only participants who had RSV detected in nasal washes or had greater than or equal to 4 fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events were included. Four vaccinees and 3 placebo recipients were excluded due to SARS CoV-2 pandemic and no post-surveillance sample. | Posted | Count of Participants | Participants | Measured pre-RSV Surveillance period (baseline) and post-RSV Surveillance period (4-6 months after the baseline) |
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From study entry to end of study. The duration of follow-up for a given participant was 2 months for Group 1 and between 6 and 10 months for Group 2 depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to Sections 7 & 8 in the Protocol Document. From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group 1: RSV 6120/∆NS2/1030s Vaccine | RSV-seropositive children will receive a single dose of 10^5.7 plaque-forming units (PFUs) of RSV 6120/∆NS2/1030s vaccine at study entry (Day 0). RSV 6120/∆NS2/1030s: Delivered as nose drops | 0 | 10 | 0 | 10 | 6 | 10 |
| EG001 | Group 1: Placebo | RSV-seropositive children will receive a single dose of placebo at study entry (Day 0). Placebo: Delivered as nose drops | 0 | 5 | 0 | 5 | 2 | 5 |
| EG002 | Group 2: RSV 6120/∆NS2/1030s Vaccine | RSV-seronegative infants and children will receive a single dose of 10^5.0 PFUs of RSV 6120/∆NS2/1030s vaccine at study entry (Day 0). RSV 6120/∆NS2/1030s: Delivered as nose drops | 0 | 20 | 0 | 20 | 20 | 20 |
| EG003 | Group 2: Placebo | RSV-seronegative infants and children will receive a single dose of placebo at study entry (Day 0). Placebo: Delivered as nose drops | 0 | 10 | 0 | 10 | 9 | 10 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eye Discharge | Eye disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| General Discomfort | General disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Bronchiolitis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
| |
| Croup | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
| |
| Otitis Media | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Rales | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Rhonchi | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Suzanne Woods, CRNP-P, CCRP, Manager, RSVPeds Team | Johns Hopkins University Bloomberg School of Public Health | (410) 614-1880 | swoods12@jhu.edu |
| Feb 23, 2023 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form: RSV-Seronegative | May 8, 2020 | Feb 23, 2023 | ICF_001.pdf |
| ICF | No | No | Yes | Informed Consent Form: RSV-Seropositive | Mar 16, 2018 | Feb 23, 2023 | ICF_002.pdf |
| ID | Term |
|---|---|
| D018357 | Respiratory Syncytial Virus Infections |
| ID | Term |
|---|---|
| D018186 | Pneumovirus Infections |
| D018184 | Paramyxoviridae Infections |
| D018701 | Mononegavirales Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
Not provided
Not provided
| 1 year of age |
|
| 2 years of age |
|
| 3 years of age |
|
| 4 years of age |
|
| > 4 years of age |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| Upper Respiratory Illness (URI) |
|
| Lower Respiratory Illness (LRI) with RSV shedding |
|
| LRI in the absence of RSV shedding |
|
| Cough without LRI |
|
| Otitis Media |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
RSV-seropositive children will receive a single dose of placebo at study entry (Day 0).
Placebo: Delivered as nose drops
|
|
RSV-seronegative infants and children will receive a single dose of placebo at study entry (Day 0).
Placebo: Delivered as nose drops
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
RSV-seronegative infants and children will receive a single dose of placebo at study entry (Day 0).
Placebo: Delivered as nose drops
|
|
| OG001 | Group 2: Placebo | RSV-seronegative infants and children will receive a single dose of placebo at study entry (Day 0). Placebo: Delivered as nose drops |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG001 | Group 2: Placebo | RSV-seronegative infants and children will receive a single dose of placebo at study entry (Day 0). Placebo: Delivered as nose drops |
|
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|