Evaluating the Infectivity, Safety, and Immunogenicity of a Respiratory Syncytial Virus Vaccine (RSV 6120/∆NS2/1030s) in RSV-Seropositive Children and RSV-Seronegative Infants and Children
- Conditions
- RSV Infection
- Interventions
- Biological: RSV 6120/∆NS2/1030sBiological: Placebo
- Registration Number
- NCT03387137
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 45
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1: RSV 6120/∆NS2/1030s Vaccine RSV 6120/∆NS2/1030s 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 2: RSV 6120/∆NS2/1030s Vaccine RSV 6120/∆NS2/1030s 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 RSV-seronegative infants and children will receive a single dose of placebo at study entry (Day 0). Group 1: Placebo Placebo RSV-seropositive children will receive a single dose of placebo at study entry (Day 0).
- Primary Outcome Measures
Name Time Method Peak Titer of Vaccine Virus Shed Measured by Reverse Transcription Polymerase Chain Reaction (RSV-seropositive Subjects) Measured at Days 0, 3, 4, 5, 6, 7 and 10 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.
Duration of Vaccine Virus Shedding in Nasal Washes (RSV-seropositive Subjects) Measured at Days 0, 3, 4, 5, 6, 7 and 10. Last day positive is reported. As determined by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)
Number of Participants With Solicited Adverse Events (AEs) by Grade - (RSV-seropositive Participants) Measured through Day 10 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.
Number of Participants With Solicited Adverse Events (AEs) by Grade - (RSV-seronegative Participants) Measured through Day 28 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.
Frequency of Infection With RSV Vaccine Virus (RSV-seronegative Subjects) Measured through Day 56 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.
Duration of Vaccine Virus Shedding in Nasal Washes (RSV-seronegative Subjects) Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28. Lat day positive is reported As determined by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)
Number of Participants With Serious Adverse Events (SAEs) (RSV-seropositive Participants) Measured through Day 28 A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that:
* Results in death during the period of protocol-defined surveillance;
* Is life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death were it more severe;
* Requires inpatient hospitalization (or prolongation of existing hospitalization): defined as at least an overnight stay in the hospital or emergency ward for treatment that would have been inappropriate if administered in the outpatient setting;
* Results in a persistent or significant disability/incapacity;
* Is a congenital anomaly or birth defect, OR
* Is an important medical event that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.Frequency of Infection With RSV Vaccine Virus (RSV-seropositive Subjects) Measured through Day 28 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.
Peak Titer of Vaccine Virus Shed by Culture (RSV-seronegative Subjects) Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28 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.
Peak Titer of Vaccine Virus Shed by Reverse Transcription Polymerase Chain Reaction (RSV-seronegative Subjects) Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28 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.
Number of Participants With Unsolicited Adverse Events (AEs) - (RSV-seropositive Participants) Measured through Day 10 Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented.
Number of Participants With Serious Adverse Events (SAEs) (RSV-seronegative Participants) Measured through Day 56 A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that:
* Results in death during the period of protocol-defined surveillance;
* Is life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death were it more severe;
* Requires inpatient hospitalization (or prolongation of existing hospitalization): defined as at least an overnight stay in the hospital or emergency ward for treatment that would have been inappropriate if administered in the outpatient setting;
* Results in a persistent or significant disability/incapacity;
* Is a congenital anomaly or birth defect, OR
* Is an important medical event that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.Peak Titer of Vaccine Virus Shed Measured by Culture (RSV-seropositive Subjects) Measured at Days 0, 3, 4, 5, 6, 7 and 10 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.
Number of Participants With Unsolicited Adverse Events (AEs) - (RSV-seronegative Participants) Measured through Day 28 Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented.
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) Measured at Day 0 and Day 56 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.
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) Measured at Day 0 and Day 28 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.
RSV-neutralizing Serum Antibody Titer and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA)(RSV-seropositive Subjects) Measured at Day 28 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.
RSV-neutralizing Serum Antibody Titers and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA) (RSV-seronegative Subjects) Measured at Day 56 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.
- Secondary Outcome Measures
Name Time Method 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 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 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
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 Measured pre- RSV Surveillance period (baseline) and post-RSV Surveillance period (4-6 months after the baseline) 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.
Number of RSV-seronegative (Group 2) Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the First RSV Season 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. 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
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 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. 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.
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 Measured pre-RSV Surveillance period (baseline) and post-RSV Surveillance period (4-6 months after the baseline) 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
Trial Locations
- Locations (1)
Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health
🇺🇸Baltimore, Maryland, United States