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

NCT04520659 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: CIR 335
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 3

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.

Conditions

RSV Infection

Outcome Measures

Primary Outcomes (7)

• Frequency of Grade 1 or Higher Solicited Adverse Events (AEs) by Grade

  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.

  Measured through Day 28

• Frequency of Grade 2 or Higher Lower Respiratory Infections (LRI) by Grade

  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.

  Measured through Day 28

• Number of Participants With Unsolicited Adverse Events (AEs) by Grade of Severity

  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 Who Experienced Serious Adverse Events (SAEs)

  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 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)

• Percentage of Vaccinees With a ≥4-fold Rise in Serum RSV-neutralizing Antibody Titer

  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.

  Measured at Day 0 and Day 56

• Peak Titer of Vaccine Virus Shed by Reverse Transcription Polymerase Chain Reaction (RT-qPCR) (Group 1 Only)

  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.

  Measured at Days 5, 7, 10, 12 and additional illness visits between Days 0 and 28.

• Number of Vaccinees Infected With RSV Vaccine Virus in Group 1

  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

  Measured through Day 56

Secondary Outcomes (3)

• 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)

• 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)

• 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

Study Arms (4)

Group 1: RSV LID/ΔM2-2/1030s

EXPERIMENTAL

Participants will receive a single dose of RSV LID/ΔM2-2/1030s vaccine at study entry (Day 0).

Biological: RSV LID/ΔM2-2/1030s

Group 1: Placebo

PLACEBO COMPARATOR

Participants will receive a single dose of placebo at study entry (Day 0).

Biological: Placebo

Group 2: RSV LID/ΔM2-2/1030s

EXPERIMENTAL

Participants will receive a single dose of RSV LID/ΔM2-2/1030s vaccine at study entry (Day 0).

Biological: RSV LID/ΔM2-2/1030s

Group 2: Placebo

PLACEBO COMPARATOR

Participants will receive a single dose of placebo at study entry (Day 0).

Biological: Placebo

Interventions

RSV LID/ΔM2-2/1030s BIOLOGICAL

10\^5 plaque-forming units (PFU); administered as nose drops

Group 1: RSV LID/ΔM2-2/1030s; Group 2: RSV LID/ΔM2-2/1030s

Placebo BIOLOGICAL

Administered as nose drops

Group 1: Placebo; Group 2: Placebo

Eligibility Criteria

• Age: 6 Months - 24 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• ≥ 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

You may not qualify if:

• ≤ 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Sanofi Pasteur, a Sanofi Company: collaborator

Study Sites (3)

John Hopkins Bloomberg School of Public Health

Baltimore, Maryland, 21205, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, 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: Suzanne Woods, CRNP-P, CCRP, Manager, RSVPeds Team
• Organization: Johns Hopkins University Bloomberg School of Public Health

swoods12@jhu.edu

(443) 813-0697

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: August 13, 2020
• First Posted: August 20, 2020
• Study Start: March 16, 2022
• Primary Completion: April 18, 2024
• Study Completion: April 18, 2024
• Last Updated: August 22, 2025
• Results First Posted: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: After publication
• Access Criteria: Qualified researchers

Locations

US (3)