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

• ClinicalTrials.gov Identifier: NCT03916185
• Recruitment Status: Active, not recruiting
• First Posted: April 16, 2019
• Last Update Posted: May 3, 2024
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

The purpose of this study is 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.

Condition or disease	Intervention/treatment	Phase
Respiratory Syncytial Virus (RSV)	Biological: RSV ΔNS2/Δ1313/I1314L Vaccine; Biological: RSV 6120/ΔNS2/1030s Vaccine; Biological: RSV 276 Vaccine; Biological: Placebo	Phase 1; Phase 2

Detailed Description:

This study will 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.

Participants will be randomly assigned to receive a single dose of RSV ΔNS2/Δ1313/I1314L vaccine, RSV 6120/ΔNS2/1030s vaccine, RSV 276 vaccine, or placebo intranasally at study entry.

Participants will be enrolled in the study outside of RSV season. All participants will remain on 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 will be between 6 and 13 months, depending on when they enroll in the study.

Participants will attend several study visits throughout the study, which may include physical examinations, blood collection, and nasal washes. Participants' parents or guardians will be contacted by study staff at various times during the study to monitor participants' health.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 67 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Randomized Phase I/II Study of 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, RSV 276 or Placebo, Delivered as Nose Drops to RSV-Seronegative Children 6 to 24 Months of Age
• Actual Study Start Date: May 16, 2019
• Actual Primary Completion Date: January 22, 2024
• Estimated Study Completion Date: April 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: RSV ΔNS2/Δ1313/I1314L Vaccine; Participants will receive a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0).	Biological: RSV ΔNS2/Δ1313/I1314L Vaccine; 10^6 plaque-forming units (PFU); administered as nose drops
Experimental: RSV 6120/ΔNS2/1030s Vaccine; Participants will receive a single dose of the RSV 6120/ΔNS2/1030s vaccine at study entry (Day 0).	Biological: RSV 6120/ΔNS2/1030s Vaccine; 10^5 plaque-forming units (PFU); administered as nose drops
Experimental: RSV 276 Vaccine; Participants will receive a single dose of the RSV 276 vaccine at study entry (Day 0).	Biological: RSV 276 Vaccine; 10^5 plaque-forming units (PFU); administered as nose drops
Placebo Comparator: Placebo; Participants will receive a single dose of placebo at study entry (Day 0).	Biological: Placebo; Administered as nose drops

Outcome Measures

Primary Outcome Measures :

1. Frequency of Grade 1 or higher solicited adverse events (AEs) [ Time Frame: Measured through Day 28 ]
   Solicited adverse events include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and are graded following a protocol-defined grading system for solicited events.
2. Frequency of Grade 2 or higher lower respiratory illnesses (LRIs) [ Time Frame: Measured through Day 28 ]
   Graded following a protocol-defined grading system for solicited events
3. Frequency of serious AEs [ Time Frame: Measured through Day 56 ]
   Serious adverse events are defined according to Version 2.0 of the DAIDS EAE Manual.
4. Frequency of a greater than or equal to 4-fold rise in serum RSV-neutralizing antibody titer [ Time Frame: Measured through Day 56 ]
   Determined from immunologic assays

Secondary Outcome Measures :

1. Frequency of a greater than or equal to 4-fold rise in serum RSV F immunoglobulin G (IgG) [ Time Frame: Measured through Day 56 ]
   Determined from immunologic assays
2. Titer of serum RSV F IgG [ Time Frame: Measured at the Day 56 Visit ]
   Determined from immunologic assays
3. Titer of serum RSV-neutralizing antibodies [ Time Frame: Measured at the Day 56 Visit ]
   Determined from immunologic assays
4. Frequency of RSV-associated medically attended acute respiratory illness (RSV-MAARI) [ Time Frame: Measured through the last day of the RSV season, which will occur between 5 and 12 months after study entry, depending on when the participant enrolls in the study ]
   Graded following a protocol-defined grading system for solicited events
5. Maximum grade (if more than one illness within a participant) of RSV-MAARI [ Time Frame: Measured through the last day of the RSV season, which will occur between 5 and 12 months after study entry, depending on when the participant enrolls in the study ]
   Graded following a protocol-defined grading system for solicited events
6. Frequency of RSV-associated medically attended acute lower respiratory illness (RSV-MAALRI) [ Time Frame: Measured through the last day of the RSV season, which will occur between 5 and 12 months after study entry, depending on when the participant enrolls in the study ]
   Graded following a protocol-defined grading system for solicited events
7. Maximum grade (if more than one illness within a participant) of RSV-MAALRI [ Time Frame: Measured through the last day of the RSV season, which will occur between 5 and 12 months after study entry, depending on when the participant enrolls in the study ]
   Graded following a protocol-defined grading system for solicited events

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 25 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Greater than or equal to 6 months (defined as greater than or equal to 180 days) of age at the time of screening and less than 25 months (defined as less than 750 days) of age at the time of enrollment.
• 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.

Exclusion Criteria:

• Prior laboratory-confirmed RSV infection.
• Known or suspected HIV infection or impairment of immunological functions.
• Receipt of immunosuppressive therapy, including any systemic, nasal, or inhaled corticosteroids within 28 days of enrollment. Note: Cutaneous (topical) steroid treatment is not an exclusion.
• 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 a person with chronic lung disease, including but not limited to chronic obstructive pulmonary disease (COPD), emphysema, or home oxygen use, reactive airway disease or asthma. Note: Asthma or reactive airway disease in a household member is not exclusionary unless the household member has taken oral steroids for asthma management in the past month and/or has been hospitalized for asthma in the past month.
• 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.
• Shares a daycare room with infants less than 4 months of age, and parent/guardian is unable or unwilling to suspend daycare for 14 days following study product administration.

• Any of the following events at the time of enrollment:

  • fever (rectal temperature of greater than or equal to 100.4°F (38°C)), or
  • upper respiratory signs or symptoms (including but not limited to rhinorrhea, cough, or pharyngitis) or
  • nasal congestion significant enough to interfere with successful study product administration, or
  • otitis media.
  • Note: if participant is randomized and subsequently noted to have any of the above, study product administration must be deferred per the study protocol.

• Receipt of the following prior to enrollment (start counting backwards with '1' as the day of planned study product administration):

  • any 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. Note: if COVID-19 vaccine has EUA approval and ACIP recommendation for this age group, it is not considered investigational

• Scheduled administration of the following after planned study product administration (start counting with '1' as the day of planned study product administration):

  • 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. Note: if COVID-19 vaccine has EUA approval and ACIP recommendation for this age group, it is not considered investigational.
• Receipt of immunoglobulin, any antibody products, or any blood products within the past 6 months prior to enrollment

• Receipt of any of the following medications within 3 days prior to study enrollment:

  • systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or
  • intranasal medications, or
  • other prescription medication except as 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.
• Born at less than 34 weeks gestation.
• Born between 34 weeks gestation and 36 weeks and 6 days gestation and less than 1 year of age at the time of enrollment.
• Current suspected or documented developmental disorder, delay, or other developmental problem.
• Any previous receipt of supplemental oxygen therapy in a home setting.
• Known or suspected SARS-CoV-2 exposure within the 14 days prior to enrollment. Note: known or suspected SARS-CoV-2 includes a known asymptomatic household member under quarantine for SARS-CoV-2 exposure but without a positive SARS-CoV-2 test.

Contacts and Locations

Locations

United States, California

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

La Jolla, California, United States, 92093-0672

Usc La Nichd Crs

Los Angeles, California, United States, 90089

David Geffen School of Medicine at UCLA NICHD CRS

Los Angeles, California, United States, 90095-1752

United States, Colorado

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, United States, 80045

United States, Georgia

Emory University School of Medicine NICHD CRS

Atlanta, Georgia, United States, 30322

United States, Illinois

Rush Univ. Cook County Hosp. Chicago NICHD CRS

Chicago, Illinois, United States, 60612

Lurie Children's Hospital of Chicago (LCH) CRS

Chicago, Illinois, United States, 60614-3393

United States, Missouri

The Children's Mercy Hospital CRS

Kansas City, Missouri, United States, 64108-4619

Center for Vaccine Development CRS

Saint Louis, Missouri, United States, 63104

United States, New York

Jacobi Med. Ctr. Bronx NICHD CRS

Bronx, New York, United States, 10461

SUNY Stony Brook NICHD CRS

Stony Brook, New York, United States, 11794

United States, North Carolina

Duke Vaccine and Trials Unit CRS

Durham, North Carolina, United States, 27705

United States, Texas

Texas Children's Hospital CRS

Houston, Texas, United States, 77030-2399

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: 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)

More Information

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT03916185
• Other Study ID Numbers: IMPAACT 2021; 38530 ( Registry Identifier: DAIDS-ES Registry Number )
• First Posted: April 16, 2019
• Last Update Posted: May 3, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Individual participant data that underlie results in the publication, after deidentification.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (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/resources/study-proposals.htm. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Virus Diseases; Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs