Safety of and Immune Response to a Cow/Human Parainfluenza Virus Vaccine (rB/HPIV3) in Healthy Infants, Children, and Adults

February 29, 2012 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Phase 1 Study of the Safety and Immunogenicity of the Recombinant Live-Attenuated Chimeric Bovine/Human Parainfluenza Type 3 Virus Vaccine, rB/HPIV3, Lot PIV3 #101A, Delivered as Nose Drops to Adults 18 to 49 Years of Age, HPIV3-Seropositive Children 15 to 59 Months of Age, and HPIV3-Seronegative Infants and Children 6 to 36 Months of Age

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, children, and adults.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

HPIV type 3 (HPIV3) ranks second only to respiratory syncytial virus as the most common 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, chimeric bovine/human, attenuated intranasal HPIV3 vaccine, rB/HPIV3. This vaccine combines modified human HPIV3 with a related, modified cow virus, bovine parainfluenza type 3 virus (BPIV3). Vaccinations will be given as nose drops to healthy adults, children seropositive for HPIV3, and infants and children seronegative for HPIV3.

There are four groups in this study. Group 1 will consist of adults who will receive the higher dose of rB/HPIV3. Group 2 will consist of seropositive children who will be randomly assigned to receive the higher dose of rB/HPIV3 or placebo. Group 2 will not begin enrollment until the completion of Group 1 safety data review. Participants of both Groups 1 and 2 will be monitored for 10 days post vaccination for respiratory illness and for fever by self-reported temperature logs; these participants will be followed for a maximum of 28 days. Blood collection will occur at study entry and on Day 28; additional blood collection may occur up to 28 days prior to vaccination. Clinical assessments and nasal washes will occur at study entry and selected study visits. Group 1 participants will be contacted by phone on Day 180; Group 2 participants' parents or guardians will be contacted by phone on Days 1, 2, 8, 9, 11, and 180; study staff will ask about any illnesses or adverse events that may have occurred.

Groups 3 and 4 will consist of seronegative infants and children. Group 3 will not begin enrollment until the completion of Group 2 safety data review. Children in Group 3 will be randomly assigned to receive the lower dose of rB/HPIV3 or placebo. Group 4 will not begin enrollment until the completion of Group 3 safety data review. Children in Group 4 will be randomly assigned to receive the higher dose of rB/HPIV3 or placebo. Participants of both Groups 3 and 4 will be monitored closely for 28 days postvaccination for respiratory illness and for fever by self-reported temperature logs; these participants will be followed for a maximum of 56 days. Blood collection will occur at study entry and on Day 56. Clinical assessments and nasal washes will occur at study entry and most study visits. Participants' parents or guardians will be contacted by phone periodically post vaccination; study staff will ask about any illnesses or adverse events they may have observed in their infants or children.

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Center for Immunization Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 months to 47 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria for Adult Participants:

  • Good general health
  • Available for the duration of the trial
  • Reachable by telephone for post-vaccination contact
  • Female participants willing to use acceptable methods of contraception

Inclusion Criteria for Seropositive Child Participants:

  • Good general health and age-appropriate development, as determined by physical exam and medical history review
  • Seropositive for human parainfluenza type 3 virus (HPIV3), as defined by a serum hemagglutination-inhibition (HI) antibody titer of more than 1:8
  • Available for the duration of the trial
  • Parent or guardian willing to provide informed consent
  • Parent or guardian reachable by telephone for post-vaccination contact

Inclusion Criteria for Seronegative Infant and Child Participants:

  • Good general health and age-appropriate development, as determined by physical exam and medical history review
  • Seronegative for HPIV3, as defined by serum HI antibody titer of 1:8 or less within 28 days of first vaccination
  • Available for the duration of the trial
  • Parent or guardian willing to provide informed consent
  • Parent or guardian reachable by telephone for post-vaccination contact

Exclusion Criteria for Adult Participants:

  • Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
  • Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the ability of the participant to understand and cooperate with the study
  • Medical, work-related, or family problems as a result of alcohol or illicit drug use in the 12 months prior to study entry
  • History of severe allergic reaction or anaphylaxis
  • Absence of spleen
  • Diagnosis of asthma within the 2 years prior to study entry
  • HIV-1 infected
  • Hepatitis C virus infected
  • Positive for hepatitis B surface antigen (HBsAg)
  • Abnormal blood or urine tests
  • Known immunodeficiency syndrome
  • Blood products, including immunoglobulin, within the 3 months prior to study entry
  • Immune globulin within 3 months of vaccination
  • Current smoker unwilling to stop smoking for the duration of the study
  • Participation in another investigational vaccine or drug trial within 30 days of vaccination or while participating in this study
  • Live vaccine within 4 weeks of vaccination
  • Killed vaccine within 2 weeks of vaccination
  • Previous immunization with PIV3 vaccine
  • Known hypersensitivity to any vaccine component
  • Other condition that, in the opinion of the investigator, would affect the participant's participation in the study
  • Work and/or personal responsibilities that involve caring for children less than 6 months of age or immunosuppressed individuals
  • Pregnancy or breastfeeding

Exclusion Criteria for Infant and All Child Participants:

  • Known or suspected impairment of immune system, including maternal history of positive HIV test, previous receipt of immunosuppressive therapy including systemic corticosteroids, or receipt of bone marrow/solid organ. Participants who have received topical steroids are not excluded.
  • Major congenital malformations, including congenital cleft palate, cytogenetic abnormalities, or serious chronic disorders
  • Previous immunization with PIV3 vaccine
  • Previous serious vaccine-associated adverse event or anaphylactic reaction
  • Lung or heart disease, including reactive airway disease. Participants with clinically insignificant cardiac abnormalities not requiring treatment are not excluded. More information on this criterion can be found in the protocol.
  • Clinically significant abnormality in liver function test (seropositive participants only)
  • Clinically significant abnormality in complete blood count (CBC) (seronegative participants only)
  • Member of a household that includes a pregnant woman, an immunocompromised individual, or an infant less than 6 months of age
  • Attends day care with infants less than 6 months of age, pregnant caregivers, or immunosuppressed individuals
  • Parent or guardian unwilling to suspend day care for 14 days following vaccination. More information on this criterion can be found in the protocol.
  • Participation in another investigational vaccine or drug trial within 30 days of first vaccination or while participating in this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
One vaccination with rB/HPIV3 vaccine (at higher dose) given as nose drops to adults 18 to 49 years of age
Biological: rB/HPIV3
Live attenuated rB/HPIV3 vaccine given at a dose of 10^6 TCID50
Biological: rB/HPIV3
Live attenuated rB/HPIV3 vaccine given at a dose of 10^5 TCID50
Experimental: 2
One vaccination with rB/HPIV3 vaccine (at higher dose) given as nose drops to HPIV3-seropositive children 15 to 59 months of age). This arm may enroll after Arm 1 depending on the effect of the vaccine on Arm 1.
Biological: rB/HPIV3
Live attenuated rB/HPIV3 vaccine given at a dose of 10^6 TCID50
Biological: rB/HPIV3
Live attenuated rB/HPIV3 vaccine given at a dose of 10^5 TCID50
Experimental: 3
One vaccination with rB/HPIV3 vaccine (at lower dose) given as nose drops to seronegative children or infants 6 to 36 months of age. This arm may enroll after Arm 2.
Biological: rB/HPIV3
Live attenuated rB/HPIV3 vaccine given at a dose of 10^6 TCID50
Biological: rB/HPIV3
Live attenuated rB/HPIV3 vaccine given at a dose of 10^5 TCID50
Experimental: 4
One vaccination with rB/HPIV3 vaccine (at higher dose) given as nose drops to seronegative children or infants 6 to 36 months of age. This arm may enroll after Arm 2.
Biological: rB/HPIV3
Live attenuated rB/HPIV3 vaccine given at a dose of 10^6 TCID50
Biological: rB/HPIV3
Live attenuated rB/HPIV3 vaccine given at a dose of 10^5 TCID50
Placebo Comparator: 5
One vaccination with placebo vaccine given as nose drops to adults, HPIV3-seropositive children, or seronegative children or infants
Biological: Placebo
Placebo for rB/HPIV3 vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Frequency of vaccine-related reactogenicity events (REs) that occur during the acute monitoring phase of the study (Days 0 to 10 for adult and seropositive groups, Days 0 to 28 for seronegative groups)
Time Frame: Throughout study
Throughout study
Quantifying the amount of vaccine virus shed by each recipient
Time Frame: Throughout study
Throughout study
Determining the amount of serum antibody and mucosal antibody induced by the vaccine in each recipient
Time Frame: Throughout study
Throughout study

Secondary Outcome Measures

Outcome Measure
Time Frame
Determining the phenotypic stability of vaccine virus shed
Time Frame: Throughout study
Throughout study
Determining the number of vaccinated children and infants infected with rB/HPIV3 vaccine virus
Time Frame: Throughout study
Throughout study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Johns Hopkins Bloomberg School of Public Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

February 1, 2011

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

August 17, 2006

First Submitted That Met QC Criteria

August 17, 2006

First Posted (Estimate)

August 21, 2006

Study Record Updates

Last Update Posted (Estimate)

March 1, 2012

Last Update Submitted That Met QC Criteria

February 29, 2012

Last Verified

February 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CIR 231
  • WIRB Protocol Number 20061455

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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