Safety and Immunogenicity of Replication-Competent Adenovirus 4-vectored Vaccine for Avian Influenza H5N1

Phase 1 Evaluation of the Safety and Immunogenicity of a Replication-Competent Adenovirus Serotype 4-vectored H5N1 Influenza Candidate Vaccine - Ad4-H5-Vtn

The purpose of this study is to compare the safety and immunogenicity over a 9-month period of five different dosages of Ad4-H5-Vtn in volunteers (Vaccinees) who receive three doses of the study vaccine or placebo. In addition, transmission of Ad4-H5-Vtn will be evaluated in all Household Contacts residing with the vaccinated volunteers.

Vaccinees also may participate in a substudy in which they receive a booster vaccination with the licensed Influenza Virus Vaccine, H5N1 (Sanofi Pasteur).

Study Overview

• Status: Completed
• Conditions: Influenza; Bird Flu
• Intervention / Treatment: Other: Placebo; Biological: Ad4-H5-Vtn; Biological: Sanofi Pasteur Influenza Virus Vaccine, H5N1

Detailed Description

At least 160 healthy Vaccinees will be randomized into 5 ascending dosage cohorts each consisting of at least 32 volunteers. In each dosage cohort Vaccinees will be randomly assigned to receive 3 doses of either Ad4-H5-Vtn or placebo separated by approximately 56 days. Volunteers will be followed for 168 days post-third vaccination.

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • The Center for Pharmaceutical Research
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy adults and their healthy adult household contacts.

Exclusion Criteria:

• Healthcare workers who have direct contact with patients who are immunodeficient, are HIV-positive, have an unstable medical condition, or are under the age of 18.
• Childcare workers who have direct contact with children 5 years old and younger.
• Resides with Household Contacts who are under the age of 18 or over the age of 65.
• Received or plans to receive licensed inactivated 2009 H1N1 influenza vaccine from 14 days prior to 14 days after any study vaccination.
• Received or plans to receive any other licensed vaccines from 30 days prior to the first study vaccination until 30 days after the third study vaccination.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; three vaccinations of 10^7vp Ad4-H5-Vtn or placebo	Other: Placebo; enteric coated capsule containing no vaccine virus; Other Names: Placebo for Ad4-H5-Vtn; Biological: Ad4-H5-Vtn; a live, replication-competent, recombinant Ad4 virus expressing the HA of H5N1 influenza (A/Vietnam/1194/2004) in an enteric capsule for oral administration; Other Names: Adenovirus Serotype 4-vectored H5N1 Influenza Vaccine; Biological: Sanofi Pasteur Influenza Virus Vaccine, H5N1; Single administration of a heterologous boost given to volunteers 3 to 15 months following their last vaccination with Ad4-H5-Vtn or placebo.; Other Names: FDA-licensed inactivated monovalent Influenza Virus Vaccine, H5N1; licensed H5N1 vaccine
Experimental: Cohort 2; three vaccinations of the 10^8vp Ad4-H5-Vtn or placebo	Other: Placebo; enteric coated capsule containing no vaccine virus; Other Names: Placebo for Ad4-H5-Vtn; Biological: Ad4-H5-Vtn; a live, replication-competent, recombinant Ad4 virus expressing the HA of H5N1 influenza (A/Vietnam/1194/2004) in an enteric capsule for oral administration; Other Names: Adenovirus Serotype 4-vectored H5N1 Influenza Vaccine; Biological: Sanofi Pasteur Influenza Virus Vaccine, H5N1; Single administration of a heterologous boost given to volunteers 3 to 15 months following their last vaccination with Ad4-H5-Vtn or placebo.; Other Names: FDA-licensed inactivated monovalent Influenza Virus Vaccine, H5N1; licensed H5N1 vaccine
Experimental: Cohort 3; three vaccinations of 10^9 Ad4-H5-Vtn or placebo	Other: Placebo; enteric coated capsule containing no vaccine virus; Other Names: Placebo for Ad4-H5-Vtn; Biological: Ad4-H5-Vtn; a live, replication-competent, recombinant Ad4 virus expressing the HA of H5N1 influenza (A/Vietnam/1194/2004) in an enteric capsule for oral administration; Other Names: Adenovirus Serotype 4-vectored H5N1 Influenza Vaccine; Biological: Sanofi Pasteur Influenza Virus Vaccine, H5N1; Single administration of a heterologous boost given to volunteers 3 to 15 months following their last vaccination with Ad4-H5-Vtn or placebo.; Other Names: FDA-licensed inactivated monovalent Influenza Virus Vaccine, H5N1; licensed H5N1 vaccine
Experimental: Cohort 4; three vaccinations of 10^10 Ad4-H5-Vtn or placebo	Other: Placebo; enteric coated capsule containing no vaccine virus; Other Names: Placebo for Ad4-H5-Vtn; Biological: Ad4-H5-Vtn; a live, replication-competent, recombinant Ad4 virus expressing the HA of H5N1 influenza (A/Vietnam/1194/2004) in an enteric capsule for oral administration; Other Names: Adenovirus Serotype 4-vectored H5N1 Influenza Vaccine; Biological: Sanofi Pasteur Influenza Virus Vaccine, H5N1; Single administration of a heterologous boost given to volunteers 3 to 15 months following their last vaccination with Ad4-H5-Vtn or placebo.; Other Names: FDA-licensed inactivated monovalent Influenza Virus Vaccine, H5N1; licensed H5N1 vaccine
Experimental: Cohort 5; three vaccinations of 10^11 Ad4-H5-Vtn or placebo	Other: Placebo; enteric coated capsule containing no vaccine virus; Other Names: Placebo for Ad4-H5-Vtn; Biological: Ad4-H5-Vtn; a live, replication-competent, recombinant Ad4 virus expressing the HA of H5N1 influenza (A/Vietnam/1194/2004) in an enteric capsule for oral administration; Other Names: Adenovirus Serotype 4-vectored H5N1 Influenza Vaccine; Biological: Sanofi Pasteur Influenza Virus Vaccine, H5N1; Single administration of a heterologous boost given to volunteers 3 to 15 months following their last vaccination with Ad4-H5-Vtn or placebo.; Other Names: FDA-licensed inactivated monovalent Influenza Virus Vaccine, H5N1; licensed H5N1 vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety, defined as the frequency and severity of vaccine-related reactogenicity events and reported AEs	Throughout trial (reactogenicity for 7 days following each vaccination)
Immunogenicity (humoral) defined by H5 HAI titer	At all available timepoints

Secondary Outcome Measures

Outcome Measure	Time Frame
Immunogenicity (humoral), defined by Ad4 antibody response	At all available timepoints
Replication/excretion of Ad4-H5-Vtn virus	Throughout trial
Transmission to household contacts as measured by AE assessment and antibody response and viral replication/excretion	Throughout trial

Collaborators and Investigators

• Sponsor: Emergent BioSolutions
• Investigators: Study Director: Marc Gurwith, M.D., J.D., Emergent BioSolutions

Publications and helpful links

General Publications

• Khurana S, Coyle EM, Manischewitz J, King LR, Ishioka G, Alexander J, Smith J, Gurwith M, Golding H. Oral priming with replicating adenovirus serotype 4 followed by subunit H5N1 vaccine boost promotes antibody affinity maturation and expands H5N1 cross-clade neutralization. PLoS One. 2015 Jan 28;10(1):e0115476. doi: 10.1371/journal.pone.0115476. eCollection 2015.
• Gurwith M, Lock M, Taylor EM, Ishioka G, Alexander J, Mayall T, Ervin JE, Greenberg RN, Strout C, Treanor JJ, Webby R, Wright PF. Safety and immunogenicity of an oral, replicating adenovirus serotype 4 vector vaccine for H5N1 influenza: a randomised, double-blind, placebo-controlled, phase 1 study. Lancet Infect Dis. 2013 Mar;13(3):238-50. doi: 10.1016/S1473-3099(12)70345-6. Epub 2013 Jan 29.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: November 2, 2009
• First Submitted That Met QC Criteria: November 2, 2009
• First Posted (Estimated): November 3, 2009

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; Vaccine; Virus Diseases
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: PXVX-H5-103-001