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Safety of and Immune Response to a Human Parainfluenza Virus Vaccine (rHPIV3cp45) in Healthy Infants

Phase 1
Completed
Conditions
Virus Diseases
Paramyxoviridae Infections
Interventions
Biological: rHPIV3cp45
Biological: Placebo
Registration Number
NCT00308412
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

Human parainfluenza viruses (HPIVs) are a major health concern in infants and young children under 5 years of age, causing serious respiratory tract disease. The purpose of this study is to test the safety of and immune response to a new HPIV vaccine in healthy infants and children.

Detailed Description

HPIV type 3 (HPIV3) ranks second only to respiratory syncytial virus as the most important cause of bronchiolitis and pneumonia in infants less than 6 months of age. HPIV3 can cause severe disease in the first 2 years of life and is responsible for 11% of hospitalizations for respiratory diseases in children. This study will evaluate the safety and immunogenicity of a live recombinant attenuated intranasal HPIV3 vaccine, rHPIV3cp45.

This study will last for a maximum of 180 days. Infants will be enrolled into one of two study groups, Group 1 or Group 2. Depending on the study location, groups will enroll either sequentially or concurrently. Within each group, infants will be randomly assigned to receive 2 immunizations of rHPIV3cp45 or placebo. Immunizations will be given as nose drops. Immunizations will be given at study entry and approximately 4 to 10 weeks after study entry.

On the day of immunization, a physical exam, vital signs measurement, blood collection, and medical history will occur. Infants will be observed for 15 minutes after immunization for any immediate adverse effects. Parents or guardians will be given a thermometer to take with them and will be instructed on how to take their infant's temperature. They will be given the study schedule and will need to provide contact phone numbers so study personnel can contact them by phone during the days after immunization. Parents and guardians will be contacted by telephone on days without study visits, from Day 1 to Day 19 and on Day 180 after immunization, and asked about any illnesses or adverse effects they have observed in their immunized infants.

Parents or guardians will need to record their infant's temperature daily for at least the 17 days immediately following immunization. During this 17-day period, there will be at least 6 study visits associated with each immunization; visits will occur on the day of immunization and approximately 3, 7, 10, 14, and 17 days after immunization. At all study visits, infants will undergo a physical exam and vital signs measurement. Group 1 participants will also undergo a nasal wash for a viral culture. There will be additional follow-up visits occurring sometime between 28 and 70 days after the first dose and 28 to 35 days after the second dose; blood collection will occur at the follow-up visits. Additional visits may be required on selected days during the month after immunization. Infants who experience illness or side effects may be asked to return to the clinic for examination. Parents or guardians will be made aware of whether their infant received the HPIV vaccine or placebo 18 days after the second immunization or in the event of a lower respiratory tract illness.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
45
Inclusion Criteria

Not provided

Exclusion Criteria
  • Known or suspected impairment of immunologic functions. Infants who are HIV infected, who are bone marrow or solid organ transplant recipients, or who are using immunosuppressive therapy, including systemic corticosteroids, are excluded. Infants who are using topical steroids, topical antibiotic ointments and topical antifungal agents are not excluded.
  • Major congenital malformations, including congenital cleft palate, cytogenetic abnormalities, or serious chronic disorders
  • Previously received PIV3 vaccine
  • Previous serious vaccine-associated adverse event or anaphylactic reaction
  • Known hypersensitivity to any vaccine component
  • Lung or heart disease, including reactive airway disease. Infants with clinically insignificant cardiac abnormalities are not excluded. Infants or children who wheezed once or received bronchodilator therapy once in the first year of life but who have not had any additional wheezing episodes or bronchodilator therapy for at least 12 months are not excluded.
  • Born prematurely before the 37th week of pregnancy
  • Member of a household containing immunocompromised individuals, pregnant caregivers, or infants less than 6 months of age
  • Attends day care with infants less than 6 months of age
  • Parent or guardian unable or unwilling to suspend daycare for 14 days following each immunization. More information on this criterion can be found in the protocol.
  • Currently enrolled in another investigational drug or vaccine study

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1rHPIV3cp45Two 10\^5 PFU doses of rHPIV3cp45 vaccine given as nose drops to healthy infants and children aged 6 to 36 months of age. The two doses are given 4 to 10 weeks apart.
2PlaceboTwo placebo vaccinations given as nose drops to healthy infants and children aged 6 to 36 months of age. The two doses are given 4 to 10 weeks apart.
Primary Outcome Measures
NameTimeMethod
Frequency of vaccine-related reactogenicity events (REs) that occur during the acute monitoring phase of the studyFor 17 days after each dose
Proportion of infants that develop fourfold or greater rises in hemagglutination-inhibition (HAI) antibody titer following two doses of vaccineThroughout study
Secondary Outcome Measures
NameTimeMethod
For the subset of infants enrolled in group 1 of the study (n=24), quantifying the amount of vaccine virus shed by each recipientThroughout study
Assessment of the immunogenicity of a second dose of vaccine and the protection of the first dose against reinfection with the second doseThroughout study
Determination of the number of vaccinated infants infected with rHPIV3cp45Throughout study
Determination of the number of vaccinated subjects infected with a second dose of rHPIV3cp45 vaccineThroughout study
Determination of the phenotypic stability of vaccine virus shedThroughout study

Trial Locations

Locations (1)

Center for Immunization Research, Johns Hopkins University

🇺🇸

Baltimore, Maryland, United States

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