Clinical Trial: Evaluating the Infectivity, Safety, and Immunogenicity of a Single Dose of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine (D46/NS2/N/ΔM2-2-HindIII) in RSV-Seronegative Infants 6 to 24 Months of Age

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase I Placebo-Controlled Study of the Infectivity, Safety and Immunogenicity of a Single Dose of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine, D46/NS2/N/ΔM2-2-HindIII, Lot

Brief Summary:

The purpose of this study is to evaluate the safety, infectivity, and immunogenicity of a single dose of a recombinant live-attenuated respiratory syncytial virus (RSV) vaccine in RSV-seronegative infants and children 6 to 24 months of age.

This study is a companion study to CIR 313.


Detailed Summary:

Human respiratory syncytial virus (RSV) is the most common viral cause of serious acute lower respiratory illness (LRI) in infants and children under 5 years of age worldwide. This study will evaluate the safety, infectivity, and immunogenicity of a single dose of RSV D46/NS2/N/ΔM2-2-HindIII, a recombinant live-attenuated RSV vaccine, in RSV-seronegative infants and children 6 to 24 months of age.

Participants will be randomly assigned to receive a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine or placebo at study entry (Day 0).

Participants will be enrolled in the study between April 1 and October 14 (outside of RSV season) and 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.


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

Current Primary Outcome:

  • Grades of study product-related solicited adverse events (AEs) [ Time Frame: Measured through Day 28 ]
    May include fever, acute otitis media, upper respiratory tract illness (URI), or lower respiratory tract Illness (LRI)
  • Grades of study product-related unsolicited AEs [ Time Frame: Measured through Day 28 ]
    Defined as all other AEs that are not solicited AEs
  • Grades of study product-related serious adverse events (SAEs) [ Time Frame: Measured through Day 56 ]
    SAEs as defined in the protocol
  • Number of participants infected with vaccine virus [ Time Frame: Measured through Day 56 ]
    Defined as 1) vaccine virus identified in a nasal wash from Study Day 0-28 (a binary outcome based on nasal washes done throughout the study period; Day 0 nasal wash will be counted as baseline) and/or 2) greater than or equal to 4-fold rise in RSV neutralizing antibody titer from Study Day 0-56
  • Peak titer of vaccine virus shed [ Time Frame: Measured through Day 28 ]
    Determined from virologic assays
  • Duration of vaccine virus shedding in nasal washes [ Time Frame: Measured through Day 28 ]
    As determined by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)
  • Frequency of a greater than or equal to 4-fold rise in RSV-neutralizing antibody titer [ Time Frame: Measured at D

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Frequency of symptomatic, medically attended respiratory and febrile illness in the vaccine and placebo recipients who experience natural infection with wt RSV during the subsequent RSV season [ Time Frame: Measured up through Month 12 ]
      Illness graded by severity based on clinical assessments
    • Frequency of antibody responses in the vaccine and placebo recipients who experience natural infection with wt RSV during the subsequent RSV season [ Time Frame: Measured up through Month 13 ]
      Determined from virologic and immunologic assays
    • Frequency of B cell responses to vaccine [ Time Frame: Measured up through Month 13 ]
      Determined from virologic and immunologic assays
    • Frequency of mucosal antibody responses to vaccine [ Time Frame: Measured up through Month 13 ]
      Determined from nasal wash samples


    Original Secondary Outcome: Same as current

    Information By: National Institute of Allergy and Infectious Diseases (NIAID)

    Dates:
    Date Received: March 23, 2017
    Date Started: March 30, 2017
    Date Completion: April 2018
    Last Updated: May 22, 2017
    Last Verified: May 2017