Evaluating the Infectivity, Safety, and Immunogenicity of Recombinant Live-Attenuated RSV Vaccines RSV ΔNS2/Δ1313/I1314L or RSV 276 in RSV-Seronegative Infants 6 to 24 Months of Age
Condition: Respiratory Syncytial Virus Infections
MeSH terms: Respiratory Syncytial Virus Infections
Intervention: RSV ΔNS2/Δ1313/I1314L; RSV 276; Placebo
Intervention description: 10^6 plaque-forming units (PFU); administered as nose drops; 10^5 PFU; administered as nose drops; Isotonic diluent, administered as nose drops
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 65.0
Sex: All
Minimum age: 6 Months
Maximum age: 24 Months
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study was to evaluate the infectivity, safety, and immunogenicity of the
      recombinant live-attenuated respiratory syncytial virus (RSV) vaccines RSV ΔNS2/Δ1313/I1314L
      or RSV 276 when delivered as nose drops to RSV-seronegative infants 6 to 24 months of age.

      This study was a companion study to Center for Immunization Research (CIR) 321.
    

Eligibility criteria:

        Inclusion Criteria:

          -  In good health based on review of the medical record, history, and physical
             examination, without evidence of chronic disease.

          -  Parent/guardian willing and able to provide written informed consent as described in
             the 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
             inoculation.

          -  Growing normally for age (i.e., not downwardly crossing two major centiles on a
             standard growth chart) in the six months prior to enrollment AND

               -  If less than 1 year of age: current height and weight above the 5th percentile

               -  If 1 year of age or older: current height and weight above the 3rd percentile for
                  age.

          -  Received routine immunizations appropriate for age (as per national Center for Disease
             Control Advisory Committee on Immunization Practices).

          -  Expected to be available for the duration of the study.

          -  If born to an HIV-infected woman, participant must not have been breastfed and 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.

        Exclusion Criteria:

          -  Known or suspected HIV infection or impairment of immunological functions.

          -  Receipt of immunosuppressive therapy, including any systemic, including either 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 receipt of a licensed or investigational RSV vaccine (or placebo in any
             International Maternal Pediatric Adolescent AIDS Clinical Trials Network RSV study) or
             previous receipt of or planned administration of any anti-RSV product (such as
             ribavirin or RSV IG or RSV mAb).

          -  Any previous anaphylactic reaction.

          -  Any previous vaccine-associated adverse reaction that was Grade 3 or above. Note: if
             grading is not possible, determine if the reaction was considered severe or life
             threatening; if so, it is exclusionary.

          -  Any known hypersensitivity to any study product component.

          -  Heart disease. Note: 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 contained, or would contain, an infant who is less than 6
             months of age at the enrollment date through Day 28.

          -  Member of a household that contained another child/other children who was/were, or
             was/were scheduled to be, enrolled in IMPAACT 2018 AND the date of enrollment to
             IMPAACT 2018 would not be concurrent with the other participant(s) living in the
             household (i.e., all eligible children from the same household must be enrolled on the
             same date).

          -  Member of a household that contained another child who was, or was scheduled to be,
             enrolled in another study evaluating an intranasal live-attenuated RSV vaccine, AND
             there has been or would be an overlap in residency during that other child's
             participation in the study's Acute Phase (Days 0 to 28).

          -  Member of a household that contained an immunocompromised individual, including, but
             not limited to:

               -  a person who was greater than or equal to 6 years of age with HIV-related
                  immunodeficiency, defined as having a most recent CD4 T lymphocyte cell count
                  less than 300 cells/mm^3. CD4 T lymphocyte count must have been measured within 6
                  months prior to enrollment for individuals with detectable virus or within 12
                  months prior to enrollment for individuals with undetectable virus, or

               -  a person age 1 year up to less than 6 years with HIV-related immunodeficiency,
                  defined as having a most recent CD4 T lymphocyte cell percentage less than 25 or
                  CD4 T lymphocyte count less than 750 cells/mm^3 (if both values are available,
                  use the lower of the two). CD4 T lymphocyte parameter must have been measured
                  within the 6 months prior to enrollment; or

               -  a person age less than 1 year with HIV-related immunodeficiency, defined as
                  having a most recent CD4 T lymphocyte cell percentage less than 30 or CD4 T
                  lymphocyte count less than 1000 cells/mm^3 (if both values are available, use the
                  lower of the two). CD4 T lymphocyte parameter must have been measured within the
                  6 months prior to enrollment; or

               -  a person who had received chemotherapy within the 12 months prior to enrollment;
                  or

               -  a person receiving immunosuppressant agents; or

               -  a person living with a solid organ or bone marrow transplant. Documenting the
                  verbal report of CD4 T cell lymphocyte count was sufficient if the
                  parent/guardian was confident of history. Individually identifiable information
                  (e.g., name) pertaining to members of the household were not collected or
                  recorded. Confirmatory laboratory tests for members of the household were not
                  ordered or collected.

          -  Attended a daycare facility and shared a room with infants less than 6 months of age,
             and parent/guardian was unable or unwilling to suspend daycare for 28 days following
             inoculation.

          -  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 (rhinorrhea, cough, or pharyngitis) or

               -  nasal congestion significant enough to interfere with successful inoculation, or

               -  otitis media.

          -  Receipt of the following prior to enrollment:

               -  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

          -  Scheduled administration 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 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.

          -  Receipt of salicylate (aspirin) or salicylate-containing products within the 28 days
             prior to enrollment.

          -  Born at less than 34 weeks gestation.

          -  Born at less than 37 weeks 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.