RSV InfectionPhase 1NCT03387137
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
A Phase 1 study testing RSV 6120/∆NS2/1030s in people with RSV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 60 monthsHealthy volunteers can take part
- Conditions the study is for
- RSV Infection
- What is being tested?
- RSV 6120/∆NS2/1030s
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Oct 2017to 31 May 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 60 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Greater than or equal to 12 months of age and less than 60 months of age at the time of inoculation
- Screening serum specimen for RSV neutralizing antibody is obtained within the calendar year of inoculation
- Seropositive for RSV antibody, defined as serum RSV neutralizing antibody titer greater than or equal to 1:40
- Pre-inoculation serum sample for RSV neutralizing antibody testing is obtained no more than 56 days prior to inoculation
- In good health based on review of the medical record, history, and physical examination at the time of inoculation
- Received routine immunizations appropriate for age based on the Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger
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- Growing normally for age as demonstrated on a standard growth chart and has a current height and weight above the 3rd percentile for age
- Expected to be available for the duration of the study
- Parent/guardian is willing and able to provide written informed consent
Who cannot join
- Born at less than 34 weeks gestation
- Maternal history of positive HIV test
- Evidence of chronic disease
- Known or suspected impairment of immune function
- Bone marrow/solid organ transplant recipient
- Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities
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- Suspected or documented developmental disorder, delay, or other developmental problem
- Cardiac abnormality requiring treatment
- Lung disease or reactive airway disease
- More than one episode of wheezing in the first year of life
- Wheezing episode or received bronchodilator therapy within the past 12 months
- Wheezing episode or received bronchodilator therapy after the age of 12 months
- Previous receipt of supplemental oxygen therapy in a home setting
- Previous receipt of an investigational RSV vaccine
- Previous receipt or planned administration of anti-RSV drug (ribavirin) or RSV antibody product including RSV immune globulin (RSV Ig) or RSV monoclonal antibody (RSV mAb)
- Previous receipt of immunoglobulin or any antibody products within the past 6 months
- Previous receipt of any other blood products within the past 6 months
- Previous anaphylactic reaction
- Previous vaccine-associated adverse reaction that was Grade 3 or above
- Known hypersensitivity to any vaccine component
- Member of a household that contains an infant who is less than 12 months of age at the date of inoculation through the 10th day after inoculation
- Member of a household that, at the date of inoculation through the 10th day after inoculation, contains an immunocompromised individual including but not limited to:
- a person who is HIV-infected
- a person who has received chemotherapy within the 12 months prior to enrollment
- a person receiving immunosuppressant agents
- a person living with a solid organ or bone marrow transplant
- Will attend a daycare facility that does not separate children by age and contains an infant who is less than 12 months of age at the date of inoculation through the 10th day after inoculation
- Receipt of any of the following prior to enrollment:
- any inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days prior, or
- any live vaccine, other than rotavirus vaccine, within the 28 days prior, or
- another investigational vaccine or investigational drug within 28 days prior, or
- salicylate (aspirin) or salicylate-containing products within the past 28 days
- Scheduled administration of any of the following after planned inoculation:
- inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days after, or
- any live vaccine other than rotavirus in the 28 days after, or
- another investigational vaccine or investigational drug in the 28 days after
- Receipt of any of the following medications within 3 days of study enrollment:
- systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or
- intranasal medications, or
- other prescription medications except the permitted concomitant medications listed below:
- Permitted concomitant medications (prescription or non-prescription) include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including (but not limited to) cutaneous (topical) steroids, topical antibiotics, and topical antifungal agents.
- Any of the following events at the time of enrollment:
- fever (temporal or rectal temperature of greater than or equal to 100.4°F), or
- upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis) or
- nasal congestion significant enough to interfere with successful inoculation, or
- otitis media
- Inclusion Criteria for RSV-Seronegative Infants and Children:
- Greater than or equal to 6 months of age and less than 25 months of age at the time of inoculation
- Screening and pre-inoculation serum specimens for RSV-neutralizing antibody are obtained no more than 42 days prior to inoculation
- Seronegative for RSV antibody, defined as serum RSV-neutralizing antibody titer less than 1:40
- In good health based on review of the medical record, history, and physical examination at the time of inoculation
- Received routine immunizations appropriate for age based on the ACIP Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger
- Growing normally for age as demonstrated on a standard growth chart, AND
- If less than 1 year of age: has a current height and weight above the 5th percentile for age
- If greater than or equal to 1 year of age: has a current height and weight above the 3rd percentile for age
- Expected to be available for the duration of the study
- Parent/guardian is willing and able to provide written informed consent
- Exclusion Criteria for RSV-Seronegative Infants and Children:
- Born at less than 34 weeks gestation
- Born at less than 37 weeks gestation, and at the date of inoculation less than 1 year of age
- Maternal history of a positive HIV test
- Evidence of chronic disease
- Known or suspected infection or impairment of immunological functions
- Bone marrow/solid organ transplant recipient
- Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities
- Suspected or documented developmental disorder, delay, or other developmental problem
- Cardiac abnormality requiring treatment
- Lung disease or reactive airway disease
- More than one episode of wheezing in the first year of life
- Wheezing episode or received bronchodilator therapy within the past 12 months
- Wheezing episode or received bronchodilator therapy after the age of 12 months
- Previous receipt of supplemental oxygen therapy in a home setting
- Previous receipt of an investigational RSV vaccine
- Previous receipt or planned administration of anti-RSV antibody product including ribavirin, RSV Ig, or RSV mAb
- Previous receipt of immunoglobulin or any antibody products within the past 6 months
- Previous receipt of any blood products within the past 6 months
- Previous anaphylactic reaction
- Previous vaccine-associated adverse reaction that was Grade 3 or above
- Known hypersensitivity to any study product component
- Member of a household that contains an infant who is less than 6 months of age at the date of inoculation through the 28th day after inoculation
- Member of a household that, at the date of inoculation through the 28th day after inoculation, contains an immunocompromised individual including but not limited to:
- a person who is HIV-infected
- a person who has cancer and has received chemotherapy within the 12 months prior to enrollment
- a person living with a solid organ or bone marrow transplant
- Attends a daycare facility that does not separate children by age and contains an infant less than 6 months of age at the date of inoculation through the 28th day after inoculation
- Receipt of any of the following prior to enrollment:
- any inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days prior, or
- any live vaccine, other than rotavirus vaccine, within the 28 days prior, or
- another investigational vaccine or investigational drug within 28 days prior, or
- salicylate (aspirin) or salicylate-containing products within the past 28 days
- Scheduled administration of any of the following after planned inoculation
- inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days after, or
- any live vaccine other than rotavirus in the 28 days after, or
- another investigational vaccine or investigational drug in the 56 days after
- Receipt of any of the following medications within 3 days of study enrollment:
- systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or
- intranasal medications, or
- other prescription medications except the permitted concomitant medications listed below:
- Permitted concomitant medications (prescription or non-prescription) include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including (but not limited to) cutaneous (topical) steroids, topical antibiotics, and topical antifungal agents.
- Any of the following events at the time of enrollment:
- fever (temporal or rectal temperature of greater than or equal to 100.4°F), or
- upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis) or
- nasal congestion significant enough to interfere with successful inoculation, or
- otitis media
- Inclusion Criteria for RSV-Seronegative Children Participating in a Second Season of RSV Surveillance:
- RSV-seronegative participants who have completed the initial RSV season surveillance portion of the study and whose parent/guardian is willing and able to provide written informed consent
- Expected to be available during the second year of RSV surveillance
- Exclusion Criteria for RSV-Seronegative Children Participating in a Second Season of RSV Surveillance:
- Currently enrolled in another RSV study
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland, 21205
About this study
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, RSV 6120/∆NS2/1030s, Lot RSV#012A, Delivered as Nose Drops to RSV-Seropositive Children 12 to 59 Months of Age and RSV-Seronegative Infants and Children 6 to 24 Months of Age
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.
Read the 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.
- Conditions
- RSV Infection
- Being tested
- RSV 6120/∆NS2/1030s, Placebo
- Medical subject headings
- Respiratory Syncytial Virus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RSV 6120/∆NS2/1030sBiological
Delivered as nose drops
PlaceboBiological
Delivered as nose drops
| Study group | Role | What they receive |
|---|---|---|
| Group 1: RSV 6120/∆NS2/1030s Vaccine | Experimental | 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). Receives: Biological: RSV 6120/∆NS2/1030s |
| Group 1: Placebo | Placebo comparator | RSV-seropositive children will receive a single dose of placebo at study entry (Day 0). Receives: Biological: Placebo |
| Group 2: RSV 6120/∆NS2/1030s Vaccine | Experimental | 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). Receives: Biological: RSV 6120/∆NS2/1030s |
| Group 2: Placebo | Placebo comparator | RSV-seronegative infants and children will receive a single dose of placebo at study entry (Day 0). Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Solicited Adverse Events (AEs) by Grade - (RSV-seropositive Participants)
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.
Measured: Measured through Day 10
Number of Participants With Solicited Adverse Events (AEs) by Grade - (RSV-seronegative Participants)
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.
Measured: Measured through Day 28
Number of Participants With Unsolicited Adverse Events (AEs) - (RSV-seropositive Participants)
Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented.
Measured: Measured through Day 10
Number of Participants With Unsolicited Adverse Events (AEs) - (RSV-seronegative Participants)
Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented.
Measured: Measured through Day 28
Number of Participants With Serious Adverse Events (SAEs) (RSV-seropositive Participants)
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.
Measured: Measured through Day 28
Number of Participants With Serious Adverse Events (SAEs) (RSV-seronegative Participants)
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.
Measured: Measured through Day 56
Frequency of Infection With RSV Vaccine Virus (RSV-seropositive Subjects)
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.
Measured: Measured through Day 28
Frequency of Infection With RSV Vaccine Virus (RSV-seronegative Subjects)
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.
Measured: Measured through Day 56
Peak Titer of Vaccine Virus Shed Measured by Culture (RSV-seropositive Subjects)
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.
Measured: Measured at Days 0, 3, 4, 5, 6, 7 and 10
Peak Titer of Vaccine Virus Shed Measured by Reverse Transcription Polymerase Chain Reaction (RSV-seropositive Subjects)
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.
Measured: Measured at Days 0, 3, 4, 5, 6, 7 and 10
Duration of Vaccine Virus Shedding in Nasal Washes (RSV-seropositive Subjects)
As determined by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)
Measured: Measured at Days 0, 3, 4, 5, 6, 7 and 10. Last day positive is reported.
Peak Titer of Vaccine Virus Shed by Culture (RSV-seronegative Subjects)
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.
Measured: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28
Peak Titer of Vaccine Virus Shed by Reverse Transcription Polymerase Chain Reaction (RSV-seronegative Subjects)
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.
Measured: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28
Duration of Vaccine Virus Shedding in Nasal Washes (RSV-seronegative Subjects)
As determined by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)
Measured: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28. Lat day positive is reported
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)
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.
Measured: Measured at Day 0 and Day 28
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)
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.
Measured: Measured at Day 0 and Day 56
RSV-neutralizing Serum Antibody Titer and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA)(RSV-seropositive Subjects)
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.
Measured: Measured at Day 28
RSV-neutralizing Serum Antibody Titers and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA) (RSV-seronegative Subjects)
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.
Measured: Measured at Day 56
Secondary outcomes (5)
Number of RSV-seronegative (Group 2) Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the First RSV Season
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
Measured: 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.
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
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.
Measured: 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.
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
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
Measured: 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
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
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.
Measured: Measured pre- RSV Surveillance period (baseline) and post-RSV Surveillance period (4-6 months after the baseline)
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
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
Measured: Measured pre-RSV Surveillance period (baseline) and post-RSV Surveillance period (4-6 months after the baseline)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2017
- Study start13 Oct 2017
- Primary completion22 Nov 2019
- Study completion31 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for RSV InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ruth A. Karron, MD, Principal investigator, Johns Hopkins Bloomberg School of Public Health (JHSPH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03387137
- Sponsor's protocol ID
- CIR 322
- Status last verified
- Nov 2024
- First submitted
- 21 Dec 2017
- Last updated
- 11 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Karron RA, Luongo C, Woods S, Oliva J, Collins PL, Buchholz UJ; RSVPed Team. Evaluation of the Live-Attenuated Intranasal Respiratory Syncytial Virus (RSV) Vaccine RSV/6120/DeltaNS2/1030s in RSV-Seronegative Young Children. J Infect Dis. 2024 Feb 14;229(2):346-354. doi: 10.1093/infdis/jiad281.
PubMed 37493269
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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, RSV 6120/∆NS2/1030s, Lot RSV#012A, Delivered as Nose Drops to RSV-Seropositive Children 12 to 59 Months of Age and RSV-Seronegative Infants and Children 6 to 24 Months of Age
- ClinicalTrials.gov ID
- NCT03387137
- Acronym / sponsor ID
- CIR 322
- Conditions
- RSV Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 13 Oct 2017 (actual)
- Primary completion
- 22 Nov 2019 (actual)
- Study completion
- 31 May 2021 (actual)
- First posted
- 29 Dec 2017 (actual)
- Results
- Posted 3 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1: RSV 6120/∆NS2/1030s Vaccine | Experimental | Biological: RSV 6120/∆NS2/1030sRSV-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 1: Placebo | Placebo comparator | Biological: PlaceboRSV-seropositive children will receive a single dose of placebo at study entry (Day 0). |
| Group 2: RSV 6120/∆NS2/1030s Vaccine | Experimental | Biological: RSV 6120/∆NS2/1030sRSV-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 comparator | Biological: PlaceboRSV-seronegative infants and children will receive a single dose of placebo at study entry (Day 0). |
Who may qualify
- Ages
- 6 to 60 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Greater than or equal to 12 months of age and less than 60 months of age at the time of inoculation
- Screening serum specimen for RSV neutralizing antibody is obtained within the calendar year of inoculation
- Seropositive for RSV antibody, defined as serum RSV neutralizing antibody titer greater than or equal to 1:40
- Pre-inoculation serum sample for RSV neutralizing antibody testing is obtained no more than 56 days prior to inoculation
- In good health based on review of the medical record, history, and physical examination at the time of inoculation
Key exclusion criteria (109 listed)
- Born at less than 34 weeks gestation
- Maternal history of positive HIV test
- Evidence of chronic disease
- Known or suspected impairment of immune function
- Bone marrow/solid organ transplant recipient
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RSV 6120/∆NS2/1030sDelivered as nose drops | Biological | Group 1: RSV 6120/∆NS2/1030s Vaccine, Group 2: RSV 6120/∆NS2/1030s Vaccine |
| PlaceboDelivered as nose drops | Biological | Group 1: Placebo, Group 2: Placebo |
Primary outcome
Number of Participants With Solicited Adverse Events (AEs) by Grade - (RSV-seropositive Participants)
Time frame: 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)
Time frame: 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.
Number of Participants With Unsolicited Adverse Events (AEs) - (RSV-seropositive Participants)
Time frame: 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 Unsolicited Adverse Events (AEs) - (RSV-seronegative Participants)
Time frame: 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 Serious Adverse Events (SAEs) (RSV-seropositive Participants)
Time frame: 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.
Number of Participants With Serious Adverse Events (SAEs) (RSV-seronegative Participants)
Time frame: 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.
Frequency of Infection With RSV Vaccine Virus (RSV-seropositive Subjects)
Time frame: 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.
Frequency of Infection With RSV Vaccine Virus (RSV-seronegative Subjects)
Time frame: 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.
Peak Titer of Vaccine Virus Shed Measured by Culture (RSV-seropositive Subjects)
Time frame: 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.
Peak Titer of Vaccine Virus Shed Measured by Reverse Transcription Polymerase Chain Reaction (RSV-seropositive Subjects)
Time frame: 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)
Time frame: 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)
Peak Titer of Vaccine Virus Shed by Culture (RSV-seronegative Subjects)
Time frame: 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)
Time frame: 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.
Duration of Vaccine Virus Shedding in Nasal Washes (RSV-seronegative Subjects)
Time frame: 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 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)
Time frame: 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.
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)
Time frame: 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.
RSV-neutralizing Serum Antibody Titer and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA)(RSV-seropositive Subjects)
Time frame: 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)
Time frame: 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.
5 secondary outcomes
Number of RSV-seronegative (Group 2) Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the First RSV Season
Time frame: 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.
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
Time frame: 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.
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
Time frame: 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
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
Time frame: Measured pre- RSV Surveillance period (baseline) and post-RSV Surveillance period (4-6 months after the baseline)
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
Time frame: Measured pre-RSV Surveillance period (baseline) and post-RSV Surveillance period (4-6 months after the baseline)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37493269Karron RA, Luongo C, Woods S, Oliva J, Collins PL, Buchholz UJ; RSVPed Team. Evaluation of the Live-Attenuated Intranasal Respiratory Syncytial Virus (RSV) Vaccine RSV/6120/DeltaNS2/1030s in RSV-Seronegative Young Children. J Infect Dis. 2024 Feb 14;229(2):346-354. doi: 10.1093/infdis/jiad281.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ruth A. Karron, MD principal investigator
Johns Hopkins Bloomberg School of Public Health (JHSPH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RSV 6120/∆NS2/1030s in people with RSV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 109 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Solicited Adverse Events (AEs) by Grade - (RSV-seropositive Participants) (time frame: Measured through Day 10). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03387137, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2024.