Safety and Immunogenicity of the RSV D46cpΔM2-2 Vaccine in RSV-Seropositive Children and RSV-Seronegative Infants and Children
- Conditions
- Respiratory Syncytial Virus Infections
- Interventions
- Biological: PlaceboBiological: D46cpΔM2-2 vaccine
- Registration Number
- NCT02601612
- Brief Summary
The purpose of this study is to evaluate the safety and immunogenicity of the RSV D46cpΔM2-2 vaccine in RSV-seropositive children and RSV-seronegative infants and children.
- Detailed Description
Human 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 and immunogenicity of the RSV D46cpΔM2-2 vaccine in RSV-seropositive children and RSV-seronegative infants and children. The vaccine will be evaluated in a stepwise fashion beginning in RSV-seropositive children (Group 1), and then in RSV-seronegative infants and children (Group 2). In each group, participants will be randomly assigned to receive a single dose of D46cpΔM2-2 vaccine or placebo at study entry (day 0).
Participants will be enrolled in the study between April 1 and October 31, outside of the RSV season. Group 1 (RSV-seropositive children) will attend several study visits and will be followed for 28 days. Group 2 (RSV-seronegative infants and children) 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 in Group 2 will also attend several study visits during the time they are enrolled in the study. Study visits for all participants may include clinical assessments, blood collection, and nasal washes.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 45
- Greater than or equal to 12 months of age and less than 60 months of age
- Received routine immunizations appropriate for age
- Serum RSV neutralizing antibody titer greater than or equal to 1:40
- Serum RSV neutralizing antibody result obtained this calendar year
- Pre-inoculation serum RSV neutralizing antibody specimen obtained less than or equal to 56 days prior to inoculation
- Parent/guardian has completed the study comprehension assessment
- Parent/guardian has signed the study informed consent document (ICD)
- Subject is expected to be available for the duration of the study
- Evidence of chronic disease
- Within the past 6 months had a decline in height or weight growth that crosses two major growth percentiles (e.g., from above the 75th to below the 25th)
- Known or suspected impairment of immune function
- Maternal history of positive HIV test
- Bone marrow/solid organ transplant recipient
- Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities
- Current or unresolved suspected or documented developmental disorder, delay, or other developmental problem
- Cardiac abnormality requiring treatment
- Lung disease or reactive airway disease
- More than one episode of wheezing in the first year of life
- Wheezing episode or received bronchodilator therapy within the past 12 months
- Previous immunization with an experimental RSV vaccine
- Previous receipt or planned administration of anti-RSV antibody product
- Previous serious vaccine-associated AE or anaphylactic reaction
- Known hypersensitivity to any vaccine component
- Previous receipt of immunoglobulin or any antibody products
- Previous receipt of any other blood products within the past 6 months
- Member of a household that contains an infant who is less than 12 months of age during study days 0 to 10
- Member of a household that includes an immunocompromised individual
- Member of a household that includes a person who has received chemotherapy within the past 12 months
- Will attend a daycare facility that does not separate children by age and contains an infant who is greater than 12 months of age during study days 0 to 10
RSV-Seronegative Infants and Children:
Inclusion Criteria:
- Greater than or equal to 6 months of age and less than 25 months of age
- Received routine immunizations appropriate for age
- Serum RSV neutralizing antibody titer is less than 1:40
- Screening and pre-inoculation serum RSV neutralizing antibody specimen obtained less than or equal to 42 days prior to inoculation
- Parent/guardian has completed the study comprehension assessment
- Parent/guardian has signed the study ICD
- Subject is expected to be available for the duration of the study
- Born at greater than or equal to 37 weeks gestation or is currently greater than 1 year of age
Exclusion Criteria:
- Evidence of chronic disease
- Within the past 6 months had a decline in height or weight growth that crosses two major growth percentiles (e.g., from above the 75th to below the 25th)
- Known or suspected impairment of immune function
- Maternal history of positive HIV test
- Bone marrow/solid organ transplant recipient
- Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities
- Current or unresolved suspected or documented developmental disorder, delay, or other developmental problem
- Cardiac abnormality requiring treatment
- Lung disease or reactive airway disease
- More than one episode of wheezing in the first year of life
- Wheezing episode or received bronchodilator therapy within the past 12 months
- Previous immunization with an experimental RSV vaccine
- Previous receipt or planned administration of anti-RSV antibody product
- Previous receipt of immunoglobulin or any antibody products
- Previous receipt of any other blood products within the past 6 months
- Previous serious vaccine-associated AE or anaphylactic reaction
- Known hypersensitivity to any vaccine component
- Member of a household which contains an infant who is less than 6 months of age during study days 0 to 28
- Member of a household that includes an immunocompromised individual
- Member of a household that includes a person who has received chemotherapy within the past 12 months
- Will attend a daycare facility that does not separate children by age and contains an infant who is less than 6 months of age during study days 0 to 28
Temporary Exclusion Criteria for RSV-Seropositive and RSV-Seronegative Children:
To be eligible to participate, RSV-seropositive and RSV-seronegative infants and children must satisfy none of the temporary exclusion criteria. The following conditions are temporary or self-limiting. Once the condition is resolved and the subject is otherwise eligible, the subject may be enrolled or rescreened, if necessary.
-
Any of the following events at the time of inoculation:
- fever (rectal temperature of greater than or equal to 100.4°F),
- upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis)
- nasal congestion significant enough to interfere with successful inoculation
- otitis media
-
Receipt of any killed vaccine or live-attenuated rotavirus vaccine less than 14 days prior to inoculation
-
Receipt of the following medications less than 28 days prior to inoculation:
- any live vaccine other than rotavirus
- another investigational vaccine or investigational drug,
- systemic corticosteroids administered for greater than 14 days at a dosage equivalent to prednisone at greater than 2 mg/kg or 20 mg daily
- salicylate (aspirin) or salicylate-containing products
-
Receipt of a non-permitted concomitant medication or any of the following medications less than 3 days prior to inoculation:
- systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis,
- intranasal medications
-
Scheduled administration of the following in relation to planned inoculation:
- killed vaccine within the 14 days following,
- any live vaccine other than rotavirus within the 28 days following,
- another investigational vaccine or drug within the 28 days following for RSV-seropositive children and the 56 days following for RSV-seronegative infants and children
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 2: Placebo Placebo RSV-seronegative infants and children will receive a single dose of placebo at study entry (day 0). Group 1: D46cpΔM2-2 Vaccine D46cpΔM2-2 vaccine RSV-seropositive children will receive a single dose of 10\^6 PFU D46cpΔM2-2 vaccine at study entry (day 0). Group 1: Placebo Placebo RSV-seropositive children will receive a single dose of placebo at study entry (day 0). Group 2: D46cpΔM2-2 Vaccine D46cpΔM2-2 vaccine RSV-seronegative infants and children will receive a single dose of 10\^5 PFU D46cpΔM2-2 vaccine at study entry (day 0).
- Primary Outcome Measures
Name Time Method Frequency of vaccine-related solicited adverse events (AEs) that occur during the acute monitoring phase of the study Measured at days 0-10 for seropositive and days 0-28 for seronegative Severity of vaccine-related solicited AEs that occur during the acute monitoring phase of the study Measured at days 0-10 for seropositive and days 0-28 for seronegative Proportion of subjects shedding vaccine virus Measured during study days 0-28 for seropositive subjects and study days 0-56 for seronegative subjects Frequency of vaccine-related lower respiratory illness Measured during study days 0-28 for seropositive subjects and study days 0-56 for seronegative subjects Proportion of subjects that develop 4-fold or greater increases in RSV neutralizing antibody titer following vaccination Measured during study days 0-28 for seropositive subjects and study days 0-56 for seronegative subjects
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Johns Hopkins Bloomberg School of Public Health
🇺🇸Baltimore, Maryland, United States