A Phase I Study to Evaluate the Safety, Reactogenicity, and Humoral Immune Responses to an Inactivated H5N1 Influenza Vaccine

A Phase I, Prospective, Randomized, Open Label, Observer-Blind, Single Center Study to Evaluate the Safety, Reactogenicity and Immunogenicity of an Inactivated H5N1 Influenza Vaccine Produced in Madin-Darby Canine Kidney (MDCK) Cells

The focus of this study is to evaluate the safety, reactogenicity and humoral immune responses of the study vaccine when administered at the dose of 7.5 µg HA, 15 µg HA, or 30 µg HA to human subjects.

Study Overview

• Status: Completed
• Conditions: Avian Influenza; Bird Flu; Influenza A(H5N1)
• Intervention / Treatment: Biological: AT-301

Detailed Description

Since 1997, avian H5N1 influenza in Southeast Asia has caused several human infections and has a high mortality rate. Experts warn that the next influenza pandemic is imminent and could be severe and prevention and control will depend on the rapid production and worldwide distribution of specific pandemic influenza candidate vaccines. An H5N1 influenza vaccine was successfully produced from whole virus grown in MDCK (Madin-Darby canine kidney) cells. These purified inactivated vaccine antigens were safe and could induce immune responses in animal studies. Moreover, when formulated in aluminum phosphate a stronger response was generated even at low doses in animals (Chong et al., 2008; Hu et al., 2008). However, further investigations are necessary before their human safety and immunogenicity can be established. This human phase I clinical study, therefore, evaluates the safety and immunogenicity of adjuvanted H5N1 virion influenza vaccine.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female ≥20 and ≤60 years of age
• In good health as determined by medical history, physical examination, and clinical judgment of the investigator
• Willing and able to comply with all required study visits and follow-up required by this protocol
• Must provide written informed consent

Exclusion Criteria:

• Known or potential exposure to avian influenza virus or any H5N1 HA antigen vaccine
• Had any influenza vaccine within 6 months
• Administered with any vaccine within 30 days
• A history of hypersensitivity to vaccines or inflammatory or degenerative neurological disease
• Receiving chronic administration of immunosuppressants or other immune-modifying drugs within 6 months
• Known HIV, hepatitis B (HBsAg) or hepatitis C seropositivity
• Any medical illness including clinically significant acute pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests
• Receiving immunoglobulins and/or any blood products within the three months
• Acute disease at the time of enrolment
• Psychiatric, addictive, or any disorder, which may compromise the ability to give a truly informed consent for participation of this study or adequate compliance
• Breast feeding or pregnant women

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dosage AT-301; 7.5 µg hemagglutinin (HA)	Biological: AT-301; Inactivated H5N1 Influenza Virion Vaccine
Experimental: Middle Dosage AT-301; 15 µg hemagglutinin (HA)	Biological: AT-301; Inactivated H5N1 Influenza Virion Vaccine
Experimental: High Dosage AT-301; 30 µg hemagglutinin (HA)	Biological: AT-301; Inactivated H5N1 Influenza Virion Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Signs and symptoms solicited by vaccination	Percentage, intensity, and relationship to vaccination of solicited local and general signs and symptoms during a 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after each administered vaccine.	A 7-day follow-up period after each vaccine administration
Signs and symptoms unsolicited by vaccination	Percentage, intensity, and relationship to vaccination of unsolicited local and general signs and symptoms during a 21-day follow-up period (i.e. day of vaccination and 20 subsequent days) after each administered vaccine.	A 21-day follow-up period after each vaccine administration
Occurrence of adverse events and serious adverse events	Occurrence of overall adverse events and serious adverse events up to 180 days after the first administered vaccine.	Up to 180 days after the first vaccine administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum antibody titers to H5N1 virus	Serum anti-HA antibody titers and neutralizing antibody titers.	Day 0
Serum antibody titers to H5N1 virus	Serum anti-HA antibody titers and neutralizing antibody titers.	Day 21
Serum antibody titers to H5N1 virus	Serum anti-HA antibody titers and neutralizing antibody titers.	Day 42

Collaborators and Investigators

• Sponsor: Medigen Biotechnology Corporation
• Investigators: Principal Investigator: Pan-Chyr Yang, MD, PhD, National Taiwan University Hospital

Publications and helpful links

General Publications

• Cheng A, Hsieh SM, Pan SC, Li YH, Hsieh EF, Lee HC, Lin TW, Lai KL, Chen C, Shi-Chung Chang S, Chang SC. The safety and immunogenicity of a cell-derived adjuvanted H5N1 vaccine - A phase I randomized clinical trial. J Microbiol Immunol Infect. 2019 Oct;52(5):685-692. doi: 10.1016/j.jmii.2019.03.009. Epub 2019 May 18.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: August 22, 2012
• First Submitted That Met QC Criteria: August 26, 2012
• First Posted (Estimate): August 29, 2012

Study Record Updates

• Last Update Posted (Estimate): October 25, 2013
• Last Update Submitted That Met QC Criteria: October 23, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Phase I; Avian Influenza; Influenza A Virus Subtype H5N1; Inactivated H5N1 Influenza Virion Vaccine; Preventive H5N1 vaccination
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Influenza in Birds
• Other Study ID Numbers: CT-AI-11