Safety and Immunogenicity of a Single Dose of the Recombinant Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccines RSV ΔNS2/Δ1313/I1314L, RSV 6120/ΔNS2/1030s, RSV 276 or Placebo, Delivered as Nose Drops to RSV-Seronegative Children 6 to 24 Months of Age

NCT03916185 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: IMPAACT 202138530
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 14

Brief Summary

The purpose of this study was to evaluate the safety and immunogenicity of a single dose of the recombinant live-attenuated respiratory syncytial virus (RSV) vaccines, RSV ΔNS2/Δ1313/I1314L, RSV 6120/ΔNS2/1030s, and RSV 276, in RSV-seronegative children 6 to 24 months of age.

Conditions

Respiratory Syncytial Virus (RSV)

Outcome Measures

Primary Outcomes (4)

• Percentage With Grade 1 or Higher Solicited Adverse Events (AEs)

  Solicited adverse events include fever, otitis media, upper respiratory illness (URI), and lower respiratory illness (LRI) and are graded following a protocol-defined grading system. Adverse events were graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. All solicited AEs with at least mild severity were included. Percentage with 95% exact confidence intervals using the Clopper-Pearson method were calculated.

  Day 0 through Day 28

• Percentage With Grade 2 or Higher Lower Respiratory Illnesses (LRIs)

  LRIs graded following a protocol-defined grading system. Adverse events were graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. All solicited LRIs with at least moderate severity were included. Percentage with 95% exact confidence intervals using the Clopper-Pearson method were calculated.

  Day 0 through Day 28

• Percentage With Serious AEs

  Serious adverse events are defined according to Version 2.0 of the DAIDS EAE Manual. A serious event is one that requires or lengthens hospitalization, that is life-threatening, that results in death, that results in a significant disability, or that is a congenital anomaly or birth defect. Percentage with 95% exact confidence intervals using the Clopper-Pearson method were calculated.

  Day 0 through Day 56

• Percentage With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titer

  Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-study product administration and Day 56 time points. Percentage with 95% exact confidence intervals (CIs) using the Clopper-Pearson method were calculated. The upper limit of the CI was compared to an a priori limit of 70%. An upper limit above 70% was considered a good vaccine candidate.

  Measured at pre-study product administration (screening) through Day 56

Secondary Outcomes (7)

• Percentage With a Greater Than or Equal to 4-fold Rise in Serum RSV F Immunoglobulin G (IgG)

  Measured at pre-study product administration (screening) and Day 56

• Titer of Serum RSV F IgG

  Measured at the Day 56 Visit

• Titer of Serum RSV-neutralizing Antibodies

  Measured at the Day 56 Visit

• Percentage With RSV-associated Medically Attended Acute Respiratory Illness (RSV-MAARI)

  Measured through the last day of the RSV season, which will occur between 5 and 15 months after study entry, depending on when the participant enrolls in the study

• Maximum Grade (if More Than One Illness Within a Participant) of RSV-MAARI

  Measured through the last day of the RSV season, which will occur between 5 and 15 months after study entry, depending on when the participant enrolls in the study

Study Arms (4)

RSV ΔNS2/Δ1313/I1314L Vaccine

EXPERIMENTAL

Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0).

Biological: RSV ΔNS2/Δ1313/I1314L Vaccine

RSV 6120/ΔNS2/1030s Vaccine

EXPERIMENTAL

Participants received a single dose of the RSV 6120/ΔNS2/1030s vaccine at study entry (Day 0).

Biological: RSV 6120/ΔNS2/1030s Vaccine

RSV 276 Vaccine

EXPERIMENTAL

Participants received a single dose of the RSV 276 vaccine at study entry (Day 0).

Biological: RSV 276 Vaccine

Placebo

PLACEBO COMPARATOR

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

Biological: Placebo

Interventions

RSV ΔNS2/Δ1313/I1314L Vaccine BIOLOGICAL

10\^6 plaque-forming units (PFU); administered as nose drops

RSV ΔNS2/Δ1313/I1314L Vaccine

RSV 6120/ΔNS2/1030s Vaccine BIOLOGICAL

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

RSV 6120/ΔNS2/1030s Vaccine

RSV 276 Vaccine BIOLOGICAL

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

RSV 276 Vaccine

Placebo BIOLOGICAL

Administered as nose drops

Placebo

Eligibility Criteria

• Age: 6 Months - 25 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• In good health based on review of the medical record, history, and physical examination, without evidence of chronic disease.
• Parent/guardian is willing and able to provide written informed consent as described in the study protocol.
• Seronegative for RSV antibody, defined as a serum RSV-neutralizing antibody titer less than 1:40 at screening from a sample collected no more than 42 days prior to study product administration.
• Note: results from specimens collected during screening for any study of an RSV vaccine developed by the Laboratory of Infectious Diseases (LID) (National Institute of Allergy and Infectious Diseases \[NIAID\], National Institutes of Health \[NIH\]) are acceptable. If study product will not be administered the same day as randomization (see the study protocol), it must be administered no more than 42 days after the screening sample is collected.
• Growing normally for age in the opinion of the site clinician in the six months prior to enrollment AND has a current height and weight above the 3rd percentile for age and sex per Centers for Disease Control and Prevention (CDC) World Health Organization (WHO) growth standards.
• Has received routine immunizations appropriate for age (as per national Center for Disease Control Advisory Committee on Immunization Practices \[ACIP\]). Note: COVID-19 vaccination will not be required unless fully licensed for this age group and ACIP-recommended. See study-specific Manual of Procedures for further guidance
• Is expected to be available for the duration of the study.
• If born to an HIV-infected woman, potential participant must have documentation of 2 negative HIV nucleic acid (RNA or DNA) test results from samples collected on different dates with both collected when greater than or equal to 4 weeks of age and at least one collected when greater than or equal to 16 weeks of age, and no positive HIV nucleic acid (RNA or DNA) test; or 2 negative HIV antibody tests, both from samples collected at greater than or equal to 24 weeks of age. If potential participant was breastfed by an HIV-infected woman, each of the sampling times noted above must be measured in weeks after the last exposure to breast milk, rather than weeks of age.

You may not qualify if:

• Prior laboratory-confirmed RSV infection.
• Known or suspected HIV infection or impairment of immunological functions.
• Any receipt of bone marrow/solid organ transplant.
• Major congenital malformations (such as congenital cleft palate) or cytogenetic abnormalities.
• Previous enrollment in this trial, previous pediatric receipt of a licensed or investigational RSV vaccine, or previous maternal or pediatric receipt of or planned administration of any other anti-RSV product (such as ribavirin or RSV IG or RSV monoclonal antibody \[mAb\]) within 4 months of screening or planned administration of an anti-RSV product between screening and day 56 after enrollment.
• Any previous anaphylactic reaction.
• Any known hypersensitivity to any study product component.
• Heart disease. Note: Potential participants with cardiac abnormalities documented to be clinically insignificant and requiring no treatment may be enrolled.
• Lung disease, including any history of reactive airway disease or medically diagnosed wheezing.
• Member of a household that contains, or will contain, an infant who is less than 4 months of age at the enrollment date through Day 14.
• Member of a household that contains another child/other children who is/are enrolled or is/are scheduled to be enrolled in IMPAACT 2021 on a different date and has/have not completed the Day 56 visit in the same calendar year (i.e., all eligible children from the same household must be enrolled/receive study product on the same date or additional children in the household may be screened, enrolled, and randomized independently after other children in the household complete the Day 56 Visit).
• Member of a household that contains another child who is, or is scheduled to be, enrolled in another study evaluating an intranasal live-attenuated RSV vaccine, AND there has been or will be an overlap in residency during Day 0 to 14 of that other child's participation in the study.
• Member of a household that contains an immunocompromised individual, including, but not limited to:
• a person who has been diagnosed with cancer and who has received chemotherapy within the 12 months prior to enrollment; or
• a person living with a solid organ, cord blood, or bone marrow transplant.

Sponsors & Collaborators

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

Study Sites (14)

David Geffen School of Medicine at UCLA NICHD CRS

Los Angeles, California, 90095-1752, United States

Location

University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program

San Diego, California, 92103, United States

Location

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, 80045, United States

Location

Emory University School of Medicine NICHD CRS

Atlanta, Georgia, 30322, United States

Location

Rush Univ. Cook County Hosp. Chicago NICHD CRS

Chicago, Illinois, 60612, United States

Location

Lurie Children's Hospital of Chicago (LCH) CRS

Chicago, Illinois, 60614-3393, United States

Location

University of Maryland School of Medicine Center for Vaccine Development CRS

Baltimore, Maryland, 21201, United States

Location

The Children's Mercy Hospital CRS

Kansas City, Missouri, 64108-4619, United States

Location

Center for Vaccine Development CRS

St Louis, Missouri, 63104, United States

Location

SUNY Stony Brook NICHD CRS

Stony Brook, New York, 11794, United States

Location

Jacobi Med. Ctr. Bronx NICHD CRS

The Bronx, New York, 10461, United States

Location

Duke Vaccine and Trials Unit CRS

Durham, North Carolina, 27703, United States

Location

Gamble Center for Clinical Studies CRS

Cincinnati, Ohio, 45229, United States

Location

Baylor College of Medicine/ Texas Children's Hospital NICHD CRS

Houston, Texas, 77030, United States

Location

Related Links

• The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1 July 2017
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

Limitations and Caveats

The study closed to enrollment prior to fully accruing. As a result, outcomes were estimated with less precision than originally planned.

Results Point of Contact

• Title: IMPAACT Clinicaltrials.gov Coordinator
• Organization: Family Health International (FHI 360)

IMPAACT.ctgov@fstrf.org

(919) 405-1429

Study Officials

• Coleen Cunningham, MD

  University of California, Irvine

  STUDY CHAIR

• Ruth Karron, MD

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

  STUDY CHAIR

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: April 10, 2019
• First Posted: April 16, 2019
• Study Start: June 20, 2019
• Primary Completion: January 22, 2024
• Study Completion: April 25, 2024
• Last Updated: February 21, 2025
• Results First Posted: February 21, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
• Access Criteria: * With whom? * Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network. * For what types of analyses? * To achieve aims in the proposal approved by the IMPAACT Network. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/studies/submit-research-proposals. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.

Locations

US (14)