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

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Center for Immunization Research
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00366782

Purpose

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.

Condition	Intervention	Phase
Paramyxoviridae Infections Virus Diseases	Biological: rB/HPIV3 Biological: Placebo	Phase I

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety Study
Official Title:	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

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
Quantifying the amount of vaccine virus shed by each recipient [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Determining the amount of serum antibody and mucosal antibody induced by the vaccine in each recipient [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Determining the phenotypic stability of vaccine virus shed [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Determining the number of vaccinated children and infants infected with rB/HPIV3 vaccine virus [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	90
Study Start Date:	March 2007
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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
2: Experimental 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
3: Experimental 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 10^5 TCID50
4: Experimental 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
5: Placebo Comparator 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

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.

Eligibility

Ages Eligible for Study:	6 Months to 49 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00366782

Locations

United States, Maryland
Center for Immunization Research	Recruiting
Baltimore, Maryland, United States, 21205
Contact: Ruth A. Karron, MD 410-614-0319 rkarron@jhsph.edu

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Center for Immunization Research

Investigators

Principal Investigator:

Ruth A. Karron, MD

Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health

More Information

Publications:

Durbin AP, Karron RA. Progress in the development of respiratory syncytial virus and parainfluenza virus vaccines. Clin Infect Dis. 2003 Dec 15;37(12):1668-77. Epub 2003 Nov 20.

Greenberg DP, Walker RE, Lee MS, Reisinger KS, Ward JI, Yogev R, Blatter MM, Yeh SH, Karron RA, Sangli C, Eubank L, Coelingh KL, Cordova JM, August MJ, Mehta HB, Chen W, Mendelman PM. A bovine parainfluenza virus type 3 vaccine is safe and immunogenic in early infancy. J Infect Dis. 2005 Apr 1;191(7):1116-22. Epub 2005 Feb 22.

Lee MS, Greenberg DP, Yeh SH, Yogev R, Reisinger KS, Ward JI, Blatter MM, Cho I, Holmes SJ, Cordova JM, August MJ, Chen W, Mehta HB, Coelingh KL, Mendelman PM. Antibody responses to bovine parainfluenza virus type 3 (PIV3) vaccination and human PIV3 infection in young infants. J Infect Dis. 2001 Oct 1;184(7):909-13. Epub 2001 Aug 15.

Madhi SA, Cutland C, Zhu Y, Hackell JG, Newman F, Blackburn N, Murphy BR, Belshe RB, Karron RA, Deatly AM, Gruber WC, Bernstein DI, Wright PF. Transmissibility, infectivity and immunogenicity of a live human parainfluenza type 3 virus vaccine (HPIV3cp45) among susceptible infants and toddlers. Vaccine. 2006 Mar 20;24(13):2432-9. Epub 2005 Dec 20.

Responsible Party:	Center for Immunization Research, Johns Hopkins School of Public Health ( Ruth A. Karron, MD )
Study ID Numbers:	CIR 231, WIRB Protocol Number 20061455
Study First Received:	August 17, 2006
Last Updated:	January 15, 2008
ClinicalTrials.gov Identifier:	NCT00366782
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Respiratory Tract Disease
Bovine
Chimeric Vaccine

Study placed in the following topic categories:

Virus Diseases
Paramyxoviridae Infections
Respiratory Tract Diseases
Healthy

Additional relevant MeSH terms:

RNA Virus Infections
Infection
Mononegavirales Infections

ClinicalTrials.gov processed this record on January 16, 2009