Infectivity, Safety and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine (D46/NS2/N/ΔM2-2-HindIII) in RSV-Seronegative Infants and Children 6 to 24 Months of Age
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|ClinicalTrials.gov Identifier: NCT03099291|
Recruitment Status : Completed
First Posted : April 4, 2017
Last Update Posted : August 31, 2018
The purpose of this study is to evaluate the safety, infectivity, and immunogenicity of a single dose of a recombinant live-attenuated respiratory syncytial virus (RSV) vaccine in RSV-seronegative infants and children 6 to 24 months of age.
This study is a companion study to IMPAACT 2013.
|Condition or disease||Intervention/treatment||Phase|
|Respiratory Syncytial Virus Infections||Biological: RSV D46/NS2/N/ΔM2-2-HindIII Vaccine Biological: Placebo||Phase 1|
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 will evaluate whether D46/NS2/N/ΔM2-2-HindIII vaccine is attenuated and immunogenic in children 6 to 24 months of age.
Participants will be randomly assigned to receive a single dose of the RSV D46/NS2/N/ΔM2-2-HindIII vaccine or placebo at study entry (Day 0).
Participants will be enrolled in the study between April 1 and October 31 (outside of RSV season) and will remain on 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 will be between 6 and 13 months, depending on when they enroll in the study. Participants will be evaluated in study visits that may include physical examinations, 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Double Blind|
|Official Title:||Phase I Placebo-Controlled Study of the Infectivity, Safety and Immunogenicity of a Single Dose of a Recombinant Live-attenuated Respiratory Syncytial Virus Vaccine, D46/NS2/N/ΔM2-2-HindIII, Lot RSV#011B, Delivered as Nose Drops to RSV-Seronegative Infants and Children 6 to 24 Months of Age|
|Actual Study Start Date :||April 1, 2017|
|Actual Primary Completion Date :||April 30, 2018|
|Actual Study Completion Date :||April 30, 2018|
Experimental: RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
Participants will receive a single dose of the RSV D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
Biological: RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
10^5 plaque-forming units (PFUs); administered as nose drops
Placebo Comparator: Placebo
Participants will receive a single dose of placebo at study entry (Day 0).
Administered as nose drops
- Grades of study product-related solicited adverse events (AEs) [ Time Frame: Measured through Day 28 ]May include fever, upper respiratory illness (URI), otitis media, or lower respiratory illness (LRI)
- Grades of study product-related unsolicited AEs [ Time Frame: Measured through Day 28 ]Defined as all other AEs that are not solicited AEs
- Grades of study product-related serious adverse events (SAEs) [ Time Frame: Measured through Day 56 ]SAEs as defined in the protocol
- Number of participants with infection with vaccine virus [ Time Frame: Measured through Day 56 ]Defined as 1) vaccine virus identified in a nasal wash from Study Day 0-28 (a binary outcome based on nasal washes done throughout the study period; Day 0 nasal wash will be counted as baseline) and/or 2) greater than or equal to 4-fold rise in RSV neutralizing antibody titer from Study Day 0-56
- Peak titer of vaccine virus shed [ Time Frame: Measured through Day 28 ]Determined from virologic assays
- Duration of vaccine virus shedding in nasal washes [ Time Frame: Measured through Day 28 ]Determined by a) culture and b) RT-PCR from Study Day 0-28
- Frequency of a greater than or equal to 4-fold rise in RSV-neutralizing antibody titer [ Time Frame: Measured through Day 56 ]Determined from virologic and immunologic assays
- Antibody responses to RSV F glycoprotein [ Time Frame: Measured through Day 56 ]As assessed by enzyme-linked immunosorbent assay (ELISA)
- Frequency of symptomatic, medically attended respiratory and febrile illness in the vaccine and placebo recipients who experience natural infection with wild-type RSV during the subsequent RSV season [ Time Frame: Measured through study completion, an average of 12 months ]Will be measured through the subsequent RSV season (November 1 in the calendar year of study entry to March 31 in the calendar year following study entry)
- Measurement of antibody responses in the vaccine and placebo recipients who experience natural infection with wt RSV during the subsequent RSV season [ Time Frame: Measured through study completion, an average of 13 months ]Will be measured at the post-RSV season visit (between April 1 and April 30 in the calendar year following study entry)
- Frequency of B cell responses to vaccine [ Time Frame: Measured through study completion, an average of 13 months ]Will be measured at the post-RSV season visit (between April 1 and April 30 in the calendar year following study entry)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03099291
|United States, Maryland|
|Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health|
|Baltimore, Maryland, United States, 21205|
|Center for Immunization Research East, Johns Hopkins Bayview Medical Center Campus|
|Baltimore, Maryland, United States, 21224|
|Center for Immunization Research South|
|Laurel, Maryland, United States, 20708|
|Principal Investigator:||Ruth Karron, MD||Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health (JHSPH)|