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, LID/ΔM2-2/1030s, in 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 respiratory syncytial virus (RSV) vaccine, LID/ΔM2-2/1030s, in RSV-seronegative infants and children 6 to 24 months of age. Participants will be randomly assigned to one of two groups to receive a single dose of intranasal RSV LID/ΔM2-2/1030s vaccine or placebo at study entry (Day 0). Group 1 (intensive) and Group 2 (less intensive) will differ only in the frequency of study visits and nasal swab collections. Participants will receive study product between April 1 and October 15, outside of the RSV season, and 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. Participants' total study duration is between 6 and 13 months, depending upon time of enrollment. Participants will attend several study visits throughout the study, which may include blood collection, nasal swabs, and physical examinations. Some of these visits may be remote if a stay at home order is put in place after enrollment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
81
10\^5 plaque-forming units (PFU); administered as nose drops
Administered as nose drops
John Hopkins Bloomberg School of Public Health
Baltimore, Maryland, United States
University of Rochester Medical Center
Rochester, New York, United States
Vanderbilt University
Nashville, Tennessee, United States
Frequency of Grade 1 or Higher Solicited Adverse Events (AEs) by Grade
Solicited adverse events include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI) as defined in Appendix III 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 16 and Table 17 in the protocol document. Details regarding LRIs will be noted in Primary Outcome Measure #2.
Time frame: Measured through Day 28
Frequency of Grade 2 or Higher Lower Respiratory Infections (LRI) by Grade
LRI may include wheezing, pneumonia, laryngotracheobronchitis (croup), rhonchi and rales as defined in Appendix III of the protocol document. A participant was only counted once in each LRI 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 16 and Table 17 in the protocol document.
Time frame: Measured through Day 28
Number of Participants With Unsolicited Adverse Events (AEs) by Grade of Severity
Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented.
Time frame: Measured through Day 28
Number of Participants Who Experienced Serious Adverse Events (SAEs)
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.
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Time frame: Measured Day 0 through Day 56 after inoculation and During the RSV Surveillance Season (Date of seasonal pause in enrollment in year of inoculation through March 31)
Percentage of Vaccinees With a ≥4-fold Rise in Serum RSV-neutralizing Antibody Titer
Serum RSV-neutralizing antibody titers were assessed by 60% RSV-plaque reduction neutralization titer (RSV-PRNT) assay. 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.
Time frame: Measured at Day 0 and Day 56
Peak Titer of Vaccine Virus Shed by Reverse Transcription Polymerase Chain Reaction (RT-qPCR) (Group 1 Only)
This is the mean of the highest value per participant of the titer of vaccine virus shed. It was measured by RT-qPCR. Group 1 participants only. Only participants who met the definition of infection with vaccine virus were included.
Time frame: Measured at Days 5, 7, 10, 12 and additional illness visits between Days 0 and 28.
Number of Vaccinees Infected With RSV Vaccine Virus in Group 1
Defined as shedding vaccine virus, detected by RT-qPCR, and/or ≥4-fold rise in RSV-specific serum antibodies, detected by enzyme-linked immunosorbent assay (ELISA) against the RSV F protein and/or an RSV-PRNT from study entry to Study Day 56
Time frame: Measured through Day 56
Frequency of RSV-medically Attended Acute Respiratory Illness (MAARI) by Grade in Vaccine and Placebo Recipients Who Experience Natural Infection With Wild Type RSV During the Subsequent 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 swabs collected during illness visits for MAARI events or a \> 2.5-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 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 16 and Table 17 in the protocol document.
Time frame: Measured during RSV season (from date of seasonal pause in enrollment in the year of inoculation through March 31)
Frequency of RSV-medically Attended Acute Lower Respiratory Illness (MAALRI) by Grade in Vaccine and Placebo Recipients Who Experience Natural Infection With Wild Type RSV During the Subsequent RSV Season
The number of participants who had RSV-associated, symptomatic, medically attended acute lower respiratory illness (MAALRI) 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 swabs collected during illness visits for MAALRI events or a ≥ 2.5-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 LRI 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 16 and Table 17 in the protocol document.
Time frame: Measured during RSV season (from date of seasonal pause in enrollment in the year of inoculation through March 31)
Percentage of Vaccinees With a ≥4-fold Rise in Serum RSV preF IgG and/or RSV postF IgG
Serum RSV preF IgG titers and RSV postF IgG titers were assessed by an Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a ≥4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.
Time frame: Measured at Day 0 and Day 56