Evaluating the Infectivity, Safety and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine, LID/ΔM2-2/1030s, in RSV-Seronegative Infants and Children 6 to 24 Months of Age

Phase 1

Completed

Conditions: RSV Infection

Interventions: Biological: RSV LID/ΔM2-2/1030s
Biological: Placebo

Registration Number: NCT04520659

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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, LID/ΔM2-2/1030s, in 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 respiratory syncytial virus (RSV) vaccine, LID/ΔM2-2/1030s, in RSV-seronegative infants and children 6 to 24 months of age.

Participants will be randomly assigned to one of two groups to receive a single dose of intranasal RSV LID/ΔM2-2/1030s vaccine or placebo at study entry (Day 0). Group 1 (intensive) and Group 2 (less intensive) will differ only in the frequency of study visits and nasal swab collections.

Participants will receive study product between April 1 and October 15, outside of the RSV season, and will remain on the study until they complete the post-RSV season visit between April 1 and April 30 in the calendar year following enrollment. Participants' total study duration is between 6 and 13 months, depending upon time of enrollment.

Participants will attend several study visits throughout the study, which may include blood collection, nasal swabs, and physical examinations. Some of these visits may be remote if a stay at home order is put in place after enrollment.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 81

Inclusion Criteria

≥ 6 months of age and <25 months of age at the time of inoculation
Screening and pre-inoculation serum specimens for respiratory syncytial virus (RSV)-neutralizing antibody are obtained no more than 42 days prior to inoculation
Seronegative for RSV antibody, defined as serum RSV-neutralizing antibody titer <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 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 World Health Organization (WHO) growth chart, AND
- If < 1 year of age: has a current height and weight above the 5th percentile for age
- If ≥ 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

≤ 6 months of age and > 25 months of age at the time of inoculation
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 before or during pregnancy
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 medically diagnosed 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 <6 months of age at the date of inoculation through the 28th day after inoculation
Receipt of any of the following prior to enrollment:
- inactivated influenza vaccine within 3 days prior, or
- any other 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 ≥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
- contact with a person diagnosed with COVID-19 disease or active severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection within the preceding 10 days

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: RSV LID/ΔM2-2/1030s	RSV LID/ΔM2-2/1030s	Participants will receive a single dose of RSV LID/ΔM2-2/1030s vaccine at study entry (Day 0).
Group 2: Placebo	Placebo	Participants will receive a single dose of placebo at study entry (Day 0).
Group 2: RSV LID/ΔM2-2/1030s	RSV LID/ΔM2-2/1030s	Participants will receive a single dose of RSV LID/ΔM2-2/1030s vaccine at study entry (Day 0).
Group 1: Placebo	Placebo	Participants will receive a single dose of placebo at study entry (Day 0).

Primary Outcome Measures

Name	Time	Method
Frequency of Grade 1 or Higher Solicited Adverse Events (AEs) by Grade	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 in Appendix III 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 16 and Table 17 in the protocol document. Details regarding LRIs will be noted in Primary Outcome Measure #2.
Frequency of Grade 2 or Higher Lower Respiratory Infections (LRI) by Grade	Measured through Day 28	LRI may include wheezing, pneumonia, laryngotracheobronchitis (croup), rhonchi and rales as defined in Appendix III of the protocol document. A participant was only counted once in each LRI 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 16 and Table 17 in the protocol document.
Number of Participants With Unsolicited Adverse Events (AEs) by Grade of Severity	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 Who Experienced Serious Adverse Events (SAEs)	Measured Day 0 through Day 56 after inoculation and During the RSV Surveillance Season (Date of seasonal pause in enrollment in year of inoculation through March 31)	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.
Percentage of Vaccinees With a ≥4-fold Rise in Serum RSV-neutralizing Antibody Titer	Measured at Day 0 and Day 56	Serum RSV-neutralizing antibody titers were assessed by 60% RSV-plaque reduction neutralization titer (RSV-PRNT) assay. 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.
Peak Titer of Vaccine Virus Shed by Reverse Transcription Polymerase Chain Reaction (RT-qPCR) (Group 1 Only)	Measured at Days 5, 7, 10, 12 and additional illness visits between Days 0 and 28.	This is the mean of the highest value per participant of the titer of vaccine virus shed. It was measured by RT-qPCR. Group 1 participants only. Only participants who met the definition of infection with vaccine virus were included.
Number of Vaccinees Infected With RSV Vaccine Virus in Group 1	Measured through Day 56	Defined as shedding vaccine virus, detected by RT-qPCR, and/or ≥4-fold rise in RSV-specific serum antibodies, detected by enzyme-linked immunosorbent assay (ELISA) against the RSV F protein and/or an RSV-PRNT from study entry to Study Day 56

Secondary Outcome Measures

Name	Time	Method
Frequency of RSV-medically Attended Acute Respiratory Illness (MAARI) by Grade in Vaccine and Placebo Recipients Who Experience Natural Infection With Wild Type RSV During the Subsequent RSV Season	Measured during RSV season (from date of seasonal pause in enrollment in the year of inoculation through March 31)	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 swabs collected during illness visits for MAARI events or a \> 2.5-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 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 16 and Table 17 in the protocol document.
Frequency of RSV-medically Attended Acute Lower Respiratory Illness (MAALRI) by Grade in Vaccine and Placebo Recipients Who Experience Natural Infection With Wild Type RSV During the Subsequent RSV Season	Measured during RSV season (from date of seasonal pause in enrollment in the year of inoculation through March 31)	The number of participants who had RSV-associated, symptomatic, medically attended acute lower respiratory illness (MAALRI) 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 swabs collected during illness visits for MAALRI events or a ≥ 2.5-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 LRI 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 16 and Table 17 in the protocol document.
Percentage of Vaccinees With a ≥4-fold Rise in Serum RSV preF IgG and/or RSV postF IgG	Measured at Day 0 and Day 56	Serum RSV preF IgG titers and RSV postF IgG titers were assessed by an Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a ≥4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.

Trial Locations

Locations (3): John Hopkins Bloomberg School of Public Health
🇺🇸
Baltimore, Maryland, United States
University of Rochester Medical Center
🇺🇸
Rochester, New York, United States
Vanderbilt University
🇺🇸
Nashville, Tennessee, United States
John Hopkins Bloomberg School of Public Health
🇺🇸Baltimore, Maryland, United States