Safety of and Immune Response to Recombinant Live Attenuated Parainfluenza Type 3 Virus Vaccine in Healthy Infants and Children

Virus Diseases Clinical Trial

Official title:

Phase I Study to Determine the Safety, Infectivity, and Tolerability of 2 Doses of Live Attenuated Recombinant Cold-Passaged (cp) 45 Human Parainfluenza Type 3 Virus Vaccine, rHPIV3cp45, Lot PIV3#102A, Delivered as Nose Drops to HPIV3-Seronegative Infants and Children 6 to 36 Months of Age, at a 6 Month Interval

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01021397
• Other study ID #: CIR 255
• Status: Completed
• Phase: Phase 1
• First received: November 25, 2009
• Last updated: December 31, 2012
• Start date: November 2009
• Est. completion date: December 2011

Study information

• Verified date: December 2012
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 primary purpose of this study is to test the safety of and immune response to a new HPIV vaccine in healthy infants and children.

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 approximately 28 weeks. Infants and children 6 months to 36 months of age will be randomly assigned to one of two groups. Group 1 participants will receive 2 immunizations of rHPIV3cp45. Group 2 participants will receive 2 doses of rHPIV3cp45 placebo. Immunizations will be given as nose drops and administered at study entry and approximately 22 to 27 weeks after study entry.

On the day of immunization, a physical exam and blood collection will occur. Participants 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 child'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 daily from Day 1 to Day 18 after each immunization.

Parents or guardians will need to record their child's temperature daily for at least 17 days immediately following immunization. During this 17-day period, study visits will occur on Days 3, 6, and 12 after each dose of vaccine or placebo. Participants will undergo a nasal wash for a viral culture at all study visits. There will be additional follow-up visits occurring sometime between 49 and 63 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 6 Months to 36 Months

Eligibility

Inclusion Criteria:

• Good general health

• HPIV3-uninfected

• Has received age-appropriate inactivated or subunit routine immunizations at least 2 weeks prior to study entry

• Has received age-appropriate live routine immunizations at least 4 weeks prior to study entry and at least 2 weeks for rotavirus and inactivated vaccines

• Available for the duration of the trial

• Parent or guardian reachable by telephone for post-immunization contact

• Parent or guardian willing to provide informed consent

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 have received immunosuppressive therapy, including systemic corticosteroids within 30 days prior to study entry. 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 HPIV3 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 if participant is currently less than 12 months of age

• 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.

• Enrolled in another investigational drug or vaccine study from 30 days prior to study entry until the final follow-up blood draw

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Paramyxoviridae Infections
• Virus Diseases

Intervention

Drug:
• rHPIV3cp45
10^5 TCID50 nasal drops
• rHPIV3cp45 placebo
1X-L15 nasal drops

Locations

Country	Name	City	State
United States	Center for Immunization Research (CIR), Johns Hopkins School of Public Health	Baltimore	Maryland
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Johns Hopkins Bloomberg School of Public Health

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

Skiadopoulos MH, Surman SR, Riggs JM, Orvell C, Collins PL, Murphy BR. Evaluation of the replication and immunogenicity of recombinant human parainfluenza virus type 3 vectors expressing up to three foreign glycoproteins. Virology. 2002 May 25;297(1):136-52. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of vaccine-related reactogenicity events and other adverse events		Throughout study	Yes
Primary	Amount of serum antibody induced by vaccine in each recipient		Throughout study	No
Secondary	Amount of vaccine virus shed by each recipient		Throughout study	No
Secondary	Immunogenicity of a second dose of vaccine and the protection of the first dose against re-infection with the second dose		From Weeks 22 to 28	No
Secondary	Number of vaccinated infants infected with rHPIV3cp45		Throughout study	Yes
Secondary	Number of vaccinated participants infected with a second dose of rHPIV3cp45		From Weeks 22 to 28	Yes
Secondary	Phenotypic stability of vaccine virus shed		Throughout study	No