Evaluating the Infectivity, Safety and Immunogenicity of Respiratory Syncytial Virus Vaccines, RSV 6120/∆NS1 and RSV 6120/F1/G2/∆NS1, in RSV-Seropositive Children and RSV-Seronegative Infants and Children

NCT03596801 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: CIR 330
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the infectivity, safety, and immunogenicity of a single dose of recombinant, live-attenuated respiratory syncytial virus (RSV) vaccines (RSV 6120/∆NS1 or RSV 6120/F1/G2/∆NS1) in RSV-seropositive children 12 to 59 months of age and RSV-seronegative infants and children 6 to 24 months of age.

Conditions

RSV Infection

Outcome Measures

Primary Outcomes (17)

• Number of Participants With Solicited Adverse Events (AEs) by Grade (RSV-seropositive Participants)

  Solicited adverse events (AE's) 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 20 and 21 in the protocol document.

  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 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 20 and Table 21 in the protocol document.

  Measured through Day 28

• Number of Participants With Unsolicited 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 through Day 10

• Number of Participants With Unsolicited 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 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 above.

  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 above.

  Measured through Day 56

• Frequency of Infection With RSV Vaccine Virus (RSV-seropositive Participants)

  Defined as 1) vaccine virus identified in nasal wash (a binary outcome based on nasal washes or done throughout the study period; Day 0 nasal wash will be counted as baseline) or 2) a greater than or equal to 4-fold rise in serum RSV neutralizing antibody titer or serum RSV F (IgG) titer from study entry to Study Day 28.

  Measured through Day 28

• Frequency of Infection With RSV Vaccine Virus (RSV-seronegative Participants)

  Defined as 1) vaccine virus identified in nasal wash or nasal swab (a binary outcome based on nasal washes or nasal swabs done throughout the study period; Day 0 nasal wash or nasal swabs will be counted as baseline) or 2) a greater than or equal to 4-fold rise in serum RSV neutralizing antibody titer or serum RSV F (IgG) titer from study entry to Study Day 56.

  Measured through Day 56

• Peak Titer of Vaccine Virus Shed by Culture (RSV-seropositive Participants)

  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 at Days 0,3,4,5,6,7 and 10.

• Peak Titer of Vaccine Virus Shed by Culture (RSV-seronegative Participants)

  This is the mean of the highest value per participant of the titer of vaccine virus (peak titer) shed measured by culture from all samples collected during the acute phase. Only participants who met the definition of infection with vaccine virus were included.

  Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28

• Duration of Virus Shedding in Nasal Washes (RSV-seropositive Participants)

  As determined by a) culture and b) reverse transcription polymerase chain reaction (rRT-PCR)

  Measured at Days 0, 3, 4, 5, 6, 7 and 10

• Duration of Virus Shedding in Nasal Washes or Nasal Swabs (RSV-seronegative Participants)

  As determined by a) culture and/or b) qPCR. Only the participants who met the definition of infection with vaccine virus were included.

  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 Titers and/or Serum Antibody Titers to RSV F Glycoprotein (RSV-seropositive Participants)

  Serum RSV-neutralizing antibody titers were assessed through an Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.

  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 Participants)

  As defined as a greater than or equal to 4-fold rise in RSV Neutralizing Antibody Titer and/or Serum 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 through Day 56

• RSV-Neutralizing Serum Antibody Titer and Immunoglobulin G (IgG) Antibody Responses to RSV F Glycoprotein (RSV-seropositive Participants)

  Serum RSV-neutralizing antibody titers to RSV F glycoprotein were assessed by glycoprotein Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined a a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.

  Measured through Day 28

• RSV-neutralizing Serum Antibody Titer and Immunoglobulin G (IgG) Antibody Responses to RSV F Glycoprotein (RSV-seronegative Participants)

  Serum Antibody Titers to RSV F Glycoprotein were assessed by Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater than or equal to 4-fold increase in titer paired specimens, between pre-inoculation and post-inoculation time points.

  Measured through Day 56

• The Frequency of Study-related Product Lower Respiratory Tract Illness (LRIs) in RSV-seropositive Participants.

  Lower respiratory tract illness (LRI) is a Solicited Adverse Event (AE) as defined in Appendix IV of the protocol document. LRI includes: wheezing, pneumonia, laryngotracheobronchitis (croup), rhonchi, rales. The number of participants who experienced LRI was presented.

  Day 0 through the 28th day following inoculation

Secondary Outcomes (4)

• 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 RSV Season

  Measured through participants' last study visit at 6 to 13 months, 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 RSV Season.

  Measured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study

• Serum RSV Antibody Titers and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA) in RSV Seronegative Subjects (Group 2) Infected With Wt-RSV During the RSV Surveillance.

  Measured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study

• Number of Participants With 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

  Measured pre-RSV Surveillance period (baseline) and post-RSV Surveillance period (4-6 months after the baseline)

Study Arms (6)

Group 1: RSV 6120/∆NS1 Vaccine

EXPERIMENTAL

Healthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of 10\^6.0 plaque-forming units (PFUs) of RSV 6120/∆NS1 vaccine at Day 0.

Biological: RSV 6120/∆NS1

Group 1: RSV 6120/F1/G2/∆NS1 Vaccine

EXPERIMENTAL

Healthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of 10\^5.8 PFUs of RSV 6120/F1/G2/∆NS1 vaccine at Day 0.

Biological: RSV 6120/F1/G2/∆NS1

Group 1: Placebo

PLACEBO COMPARATOR

Healthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of placebo at Day 0.

Biological: Placebo

Group 2: RSV 6120/∆NS1 Vaccine

EXPERIMENTAL

Healthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of 10\^5.0 PFUs of RSV 6120/∆NS1 vaccine at Day 0.

Biological: RSV 6120/∆NS1

Group 2: RSV 6120/F1/G2/∆NS1

EXPERIMENTAL

Healthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of 10\^5.0 PFUs of RSV 6120/F1/G2/∆NS1 vaccine at Day 0.

Biological: RSV 6120/F1/G2/∆NS1

Group 2: Placebo

PLACEBO COMPARATOR

Healthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of placebo at Day 0.

Biological: Placebo

Interventions

RSV 6120/∆NS1 BIOLOGICAL

Delivered as nose drops

Group 1: RSV 6120/∆NS1 Vaccine; Group 2: RSV 6120/∆NS1 Vaccine

RSV 6120/F1/G2/∆NS1 BIOLOGICAL

Delivered as nose drops

Group 1: RSV 6120/F1/G2/∆NS1 Vaccine; Group 2: RSV 6120/F1/G2/∆NS1

Placebo BIOLOGICAL

Delivered as nose drops

Group 1: Placebo; Group 2: Placebo

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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 specimen is obtained no more than 56 days prior to inoculation
• In good health based on review of the medical record, history, and physical examination (PE) 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
• 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

You may not qualify if:

• Born at less than 34 weeks gestation
• Maternal history of positive human immunodeficiency virus (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
• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Johns Hopkins University Center for Immunization Research

Baltimore, Maryland, 21205, United States

Location

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Ruth A. Karron, MD
• Organization: Johns Hopkins Bloomberg School of Public Health (JHSPH)

rkarron@jhu.edu

410-614-0319

Study Officials

• Ruth A. Karron, MD

  Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health (JHSPH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2018
• First Posted: July 24, 2018
• Study Start: June 29, 2018
• Primary Completion: April 25, 2024
• Study Completion: April 25, 2024
• Last Updated: February 13, 2026
• Results First Posted: February 13, 2026

Record last verified: 2026-01

Locations

US (1)