Evaluating the Infectivity, Safety, and Immunogenicity of a Single Dose of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine (D46/NS2/N/ΔM2-2-HindIII) in RSV-Seronegative Infants 6 to 24 Months of Age
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|ClinicalTrials.gov Identifier: NCT03102034|
Recruitment Status : Completed
First Posted : April 5, 2017
Results First Posted : June 14, 2019
Last Update Posted : December 11, 2019
The purpose of this study was 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 was a companion study to CIR 313.
|Condition or disease||Intervention/treatment||Phase|
|Respiratory Syncytial Virus Infections||Biological: D46/NS2/N/ΔM2-2-HindIII 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 evaluated the safety, infectivity, and immunogenicity of a single dose of RSV D46/NS2/N/ΔM2-2-HindIII, a recombinant live-attenuated RSV vaccine, in RSV-seronegative infants and children 6 to 24 months of age.
Participants were randomly assigned to receive a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine or placebo (administered as nose drops) at study entry (Day 0).
Participants could be enrolled in the study outside of RSV season (between April 1 and October 14 for most sites or-for sites with local RSV seasons that start earlier-as specified on a site-by-site basis in the Manual Of Procedures). All participants 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 13 months, depending on when they enrolled in the study. Participants attended several study visits throughout the study, which included 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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 6 to 24 Months of Age|
|Actual Study Start Date :||April 6, 2017|
|Actual Primary Completion Date :||May 25, 2018|
|Actual Study Completion Date :||May 25, 2018|
Experimental: RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
10^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
Placebo Comparator: Placebo
Participants received a single dose of placebo at study entry (Day 0).
Isotonic diluent; administered as nose drops
- Number of Participants With Solicited Adverse Events (AEs) by Grade [ Time Frame: Measured from Day 0 through Day 28 ]Solicited adverse events included 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 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 3 and Table 4 in the protocol document.
- Number of Participants With Unsolicited AEs by Grade [ Time Frame: Measured from Day 0 through Day 28 ]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 was 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).
- Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Measured from Day 0 through Day 56 ]
A Serious Adverse Event (SAE) was an AE, whether considered related to the study product or not, that:
- Resulted in death during the period of protocol-defined surveillance
- Was life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it did not refer to an event that hypothetically might have caused death were it more severe
- Required 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
- Resulted in a persistent or significant disability/incapacity
- Was a congenital anomaly or birth defect
- Was an important medical event that might not be immediately life threatening or result in death or hospitalization but might jeopardize the patient or might require intervention to prevent one of the outcomes listed above.
- Number of Participants Infected With RSV Vaccine Virus [ 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 ]Defined as 1) vaccine virus identified in a nasal wash from Study Day 0-28 (a binary outcome based on nasal washes) and/or 2) greater than or equal to 4-fold rise in RSV-neutralizing antibody titer from Study Day 0 and 56.
- Peak Titer of Vaccine Virus Shed [ Time Frame: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28 ]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.
- Duration of Vaccine Virus Shedding in Nasal Washes [ Time Frame: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28. Last day positive is reported. ]Determined separately by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)
- Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titer [ Time Frame: Measured at Day 0 and Day 56 ]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-inoculation and post-inoculation time points.
- Serum Antibody Responses to RSV F Glycoprotein as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) [ Time Frame: Measured at Day 56 ]Immunogenicity was assessed at approximately 2 months post-inoculation (Study Day 56).
- Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season [ Time Frame: Measured from November 1st through participant's post-RSV season surveillance visit ]The number of participants who had RSV-associated, medically attended, acute respiratory illness (RSV-MAARI) or RSV-associated, medically attended, acute lower respiratory illness (RSV-MAALRI) among those who had RSV detected in nasal washes or greater than or equal to 4 fold rise in serum antibodies during the subsequent RSV season were presented.
- Magnitude of Serum RSV-neutralizing Antibody Responses in the Vaccine and Placebo Recipients Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season. [ Time Frame: Measured through participant's last study visit, up to a total of 6 to 13 months depending on when participants enrolled in the study ]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.
- Number of Participants With B Cell Responses to Vaccine [ Time Frame: Measured at day 0 and Day 56 ]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.
- Frequency of Mucosal Antibody Responses to Vaccine [ Time Frame: Measured at Day 0, 28 and 56 ]Determined from nasal wash samples. Reliably quantifying RSV specific antibodies in dilute nasal washes and SAM strips continues to be difficult. We are currently upgrading to a next-generation assay reader with superior sensitivity, and we have improved a DELFIA assay. Due to these challenges, the final results are not available at this time. The results will be posted when available, after passing quality assurance and control reviews at the testing laboratory and at the data management center.
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): NCT03102034
|United States, California|
|Usc La Nichd Crs|
|Los Angeles, California, United States, 90089|
|David Geffen School of Medicine at UCLA NICHD CRS|
|Los Angeles, California, United States, 90095-1752|
|United States, Colorado|
|Univ. of Colorado Denver NICHD CRS|
|Aurora, Colorado, United States, 80045|
|United States, Georgia|
|Emory University School of Medicine NICHD CRS|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|Rush Univ. Cook County Hosp. Chicago NICHD CRS|
|Chicago, Illinois, United States, 60612|
|Lurie Children's Hospital of Chicago (LCH) CRS|
|Chicago, Illinois, United States, 60614-3393|
|United States, Maryland|
|Johns Hopkins University Center for Immunization Research|
|Baltimore, Maryland, United States, 21205|
|United States, New York|
|Jacobi Med. Ctr. Bronx NICHD CRS|
|Bronx, New York, United States, 10461|
|SUNY Stony Brook NICHD CRS|
|Stony Brook, New York, United States, 11794|
|United States, Tennessee|
|St. Jude Children's Research Hospital CRS|
|Memphis, Tennessee, United States, 38105-3678|
|Study Chair:||Elizabeth (Betsy) J. McFarland, MD||University of Colorado School of Medicine and Children's Hospital Colorado, Pediatric Infectious Diseases|