Phase I Placebo-Controlled Study of the Infectivity, Safety and Immunogenicity of a Single Dose of a Recombinant Live-attenuated Respiratory Syncytial Virus Vaccine, LID ΔM2-2 1030s, Lot RSV#010A, Delivered as Nose Drops to RSV-Seronegative Infants and Children 6 to 24 Months of Age
Phase I Placebo-Controlled Study of the Infectivity, Safety and Immunogenicity of a Single Dose of a Recombinant Live-attenuated Respiratory Syncytial Virus Vaccine, LID ΔM2-2 1030s, Lot RSV#010A, Delivered as Nose Drops to RSV-Seronegative Infants and Children 6 to 24 Months of Age
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 6 to 24 months of age.
This study is a companion study to IMPAACT 2011.
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. The purpose of this study is to evaluate the safety, infectivity, and immunogenicity of a single dose of a recombinant live-attenuated RSV vaccine, RSV LID ΔM2-2 1030s, in RSV-seronegative infants 6 to 24 months of age.
Participants will be randomly assigned to receive a single dose of the RSV LID ΔM2-2 1030s vaccine or placebo (administered as nose drops) at study entry (Day 0).
Participants will be enrolled in the study between April 1 and October 31, outside of the 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. Total study duration is between 6 to 13 months, depending on when participants enroll in the study. Participants will attend several study visits throughout the study, and the visits may include blood collection, nasal washes, and physical examinations. Participants' parents or guardians will be contacted by study staff at various times during the study to monitor participants' health.
Inclusion Criteria:
Greater than or equal to 6 months (greater than or equal to 180 days) of age at the time of screening and less than 25 months (less than 750 days) of age
Participant is in good health based on review of the medical record, history, and physical examination, without evidence of chronic disease
Parents/guardians are willing and able to provide written informed consent
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
Is growing at a normal velocity for age as demonstrated on a standard growth chart AND
Participant has received routine immunizations appropriate for age (as per Center for Disease Control Advisory Committee on Immunization Practices [ACIP])
Participant is expected to be available for the duration of the study
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.
Bone marrow/solid organ transplant recipient
Major congenital malformations (such as congenital cleft palate) or cytogenetic abnormalities
Previous receipt of a licensed or investigational RSV vaccine or receipt of placebo in this study or previous receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV IG)
Previous anaphylactic reaction
Previous vaccine-associated adverse reaction that was Grade 3 or above
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 documented wheezing
Member of a household that contains, or will contain, an infant who is less than 6 months of age at the enrollment date through Day 28
Member of a household that contains another child who is, or is scheduled to be, enrolled in CIR 311, 312 or 313 AND there has been or will 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 contains an immunocompromised individual, including but not limited to:
Attends a daycare facility and shares a room with infants less than 6 months of age, and parent/guardian is unable or unwilling to suspend daycare for 28 days following inoculation
Any of the following events at the time of enrollment:
Receipt of the following prior to enrollment:
Scheduled administration of the following after planned inoculation:
Receipt of immunoglobulin, any antibody products, or any blood products within the past 6 months
Receipt of any of the following medications within 3 days of study enrollment:
Receipt of salicylate (aspirin) or salicylate-containing products within the past 28 days
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
Meets criteria for failure to thrive within the six months prior to enrollment: a decline in height or weight growth that has crossed two major growth percentiles (e.g., from above the 75th to below the 25th) in an interval of less than 6 months
Suspected or documented developmental disorder, delay, or other developmental problem
Previous receipt of supplemental oxygen therapy in a home setting