The purpose of this study was to evaluate the safety, infectivity, and immunogenicity of a single intranasal dose of a recombinant live-attenuated respiratory syncytial virus (RSV) vaccine in RSV-seronegative infants 6 to 24 months of age. This study was a companion study to CIR 312.
Human respiratory syncytial virus (RSV) is the most common viral cause of serious acute lower respiratory illness (LRI) in infants and children under 5 years of age worldwide. This study evaluated the safety, infectivity, and immunogenicity of a single dose of RSV LID cp ΔM2-2, a recombinant live-attenuated RSV vaccine, in RSV-seronegative infants 6 to 24 months of age. Participants were randomly assigned to receive a single dose of the RSV LID cp ΔM2-2 vaccine or placebo at study entry (Day 0). Participants were enrolled in the study between April 1 and October 14 (outside of RSV season) and remained on study until they completed the post-RSV season visit between April 1 and April 30 in the calendar year following enrollment. Participants' total study duration was between 6 and 10 months, depending on when they enrolled in the study. Participants attended several study visits throughout the study, which may include physical examinations, blood collection, and nasal washes. Participants' parents or guardians were contacted by study staff at various times during the study to monitor participants' health. The study was closed to accrual early after interim data were reviewed by a subset of protocol team members and it was concluded that this vaccine candidate will not meet the criteria listed in the protocol for a good vaccine candidate. This recommendation was shared with the (blinded) protocol chair and the Medical Officers, as well as the Data Safety and Monitoring Board (DSMB), who agreed with the unblinded protocol team members' assessment. The targeted sample size was 33 (22 in the vaccine arm and 11 in the placebo arm). Participants already on study at the time of the early closing decision remained on study and completed the follow-up per protocol.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
10\^5 plaque-forming units (PFUs); administered as nose drops
Isotonic diluent, administered as nose drops
David Geffen School of Medicine at UCLA NICHD CRS
Los Angeles, California, United States
Univ. of Colorado Denver NICHD CRS
Aurora, Colorado, United States
Rush Univ. Cook County Hosp. Chicago NICHD CRS
Chicago, Illinois, United States
Johns Hopkins University Center for Immunization Research
Baltimore, Maryland, United States
Number of Participants With 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). 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 3 and Table 4 in the protocol document.
Time frame: Measured from Day 0 through Day 28
Number of Participants With Unsolicited AEs by Grade
Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each unsolicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. AE grading (Grade 1- mild to Grade 4-life-threatening) was done by DAIDS AE Grading table v2.0 (see References).
Time frame: Measured from Day 0 through Day 28
Number of Participants With Serious Adverse Events (SAEs)
A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that: 1. Results in death during the period of protocol-defined surveillance 2. 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 3. 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 4. Results in a persistent or significant disability/incapacity 5. Is a congenital anomaly or birth defect 6. 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.
Time frame: Measured from Day 0 through Day 56
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QUADRUPLE
Enrollment
17
Philadelphia IMPAACT Unit CRS
Philadelphia, Pennsylvania, United States
Number of Participants Infected With RSV Vaccine
Defined as 1) vaccine virus identified in a nasal wash from Study Day 0-28 (a binary outcome based on nasal washes) or 2) greater than or equal to 4-fold rise in serum RSV-neutralizing antibody titer between Study Days 0 and 56.
Time frame: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28 for nasal washes, and at Days 0, 56 for serum RSV-neutralizing antibodies
Peak Titer of Vaccine Virus Shed
This is 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.
Time frame: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28
Duration of Virus Shedding in Nasal Washes
Determined separately by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)
Time frame: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28. Last day positive is reported.
Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titer
Immunogenicity was assessed pre-inoculation, and at approximately 2 months post-inoculation (Study Day 56). Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre and post time points.
Time frame: Measured at Day 0 and Day 56
Serum Antibody Responses to RSV F Glycoprotein as Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
Immunogenicity was assessed at approximately 2 months post-inoculation (Study Day 56).
Time frame: Measured at Day 56
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season
The number of participants who had symptomatic, medically attended respiratory and febrile illness among those who had RSV detected in nasal washes or \>=4 fold rise in serum antibodies during the subsequent RSV season were presented. A participant was only counted once in each solicited AE category, and that was in the line corresponding to the highest grade adverse event they had in that category.
Time frame: Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enroll in the study
Magnitude of Serum RSV-neutralizing Antibody Responses in the Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the Subsequent RSV Season.
Only participants who had RSV detected in nasal washes or a greater than or equal to 4-fold rise in serum antibodies during the subsequent RSV season were included. RSV-neutralizing antibody titers were measured pre- and post-RSV surveillance season.
Time frame: Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enroll in the study
Number of Participants With B Cell Responses to Vaccine
A B cell response to vaccine is indicated by a greater than or equal to 4-fold change in serum antibody titers to RSV F glycoprotein between the pre- and post-inoculation time points, and between pre- and post-RSV surveillance time points.
Time frame: Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enroll in the study