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

NCT03387137 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: CIR 322
• Study Type: interventional
• Target: 45
• 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 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.

Conditions

RSV Infection

Outcome Measures

Primary Outcomes (18)

• 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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

  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

  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

  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

  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

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

Study Arms (4)

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).

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).

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).

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).

Biological: Placebo

Interventions

RSV 6120/∆NS2/1030s BIOLOGICAL

Delivered as nose drops

Group 1: RSV 6120/∆NS2/1030s Vaccine; Group 2: RSV 6120/∆NS2/1030s Vaccine

Placebo BIOLOGICAL

Delivered as nose drops

Group 1: Placebo; Group 2: Placebo

Eligibility Criteria

• Age: 6 Months - 60 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 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
• 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 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 drug (ribavirin) or RSV antibody product including RSV immune globulin (RSV Ig) or RSV monoclonal antibody (RSV mAb)

Sponsors & Collaborators

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

Study Sites (1)

Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health

Baltimore, Maryland, 21205, United States

Location

Related Publications (1)

• 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.

  PMID: 37493269 RESULT

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: Suzanne Woods, CRNP-P, CCRP, Manager, RSVPeds Team
• Organization: Johns Hopkins University Bloomberg School of Public Health

swoods12@jhu.edu

(410) 614-1880

Study Officials

• Ruth A. Karron, MD

  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: December 21, 2017
• First Posted: December 29, 2017
• Study Start: October 13, 2017
• Primary Completion: November 22, 2019
• Study Completion: May 31, 2021
• Last Updated: December 11, 2024
• Results First Posted: August 3, 2023

Record last verified: 2024-11

Locations

US (1)