Safety and Immunogenicity of an Inactivated Pandemic Influenza Vaccine

The Clinical Trial of Pandemic Influenza Vaccine (Whole-Virion， Inactivated, Adjuvanted) on Healthy Adults by Randomized and Double-Blind Design: a Phase II Study

A single center, randomized and double-blind phase II clinical trial is to be conducted in adults to evaluate the safety and immunogenicity of an inactivated pandemic influenza vaccine (whole-virion, aluminium-adjuvanted).

Study Overview

• Status: Completed
• Conditions: Prevention; Pandemic Influenza
• Intervention / Treatment: Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14)

Detailed Description

The vaccine to be investigated is producted in embryonated hen's eggs using an H5N1 reference strain NIBRG-14 which was prepared by NIBSC. The strain is a reassortant between A/Vietnam/1194/2004 and A/PR/8/34 by reverse genetics.

Total 400 volunteers aged from 18 to 60 years old are to be enrolled with 100 subjects in each group. The eligible volunteers will receive two doses vaccine of 5μg，10μg or 15μg haemagglutinin antigen. The schedule is day 0,14 or day 0,28. The subjects will donate their blood samples for the detection of HI antibody and microneutralization antibody. Local and systematic adverse reactions will be recorded during the study.

• Study Type: Interventional
• Enrollment (Actual): 402
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adults aged 18-60 years old
• Be able to show legal identity card for the sake of recruitment
• Be able to understand and sign the informed consent.

Exclusion Criteria:

• Woman： Who breast-feeding or planning to become pregnant during the 56 days of study participation
• Any history of allergic reactions was allergic to any component of the vaccine, such as eggs or ovalbumin;
• Any history of severe adverse reactions to vaccines, such as anaphylaxis, hives, respiratory difficulty, angioedema, or abdominal pain
• Autoimmune disease or immunodeficiency
• Asthma that is unstable or required emergent care, hospitalization or intubation during the past two years or that required the use of oral or intravenous corticosteroids
• Diabetes mellitus (type I or II), with the exception of gestational diabetes
• History of thyroidectomy or thyroid disease that required medication within the past 12 months
• Serious angioedema episodes within the previous 3 years or requiring medication in the previous two years
• Hypertension that was not well controlled by medication or is more than 145/95 mmHg at enrollment
• Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws
• Active malignancy or treated malignancy for which there is not reasonable assurance of sustained cure or malignancy that is likely to recur during the period of study

• Seizure disorder other than:

  1. Febrile seizures under the age of two years old,
  2. Seizures secondary to alcohol withdrawal more than 3 years ago, or
  3. A singular seizure not requiring treatment within the last 3 years
• Asplenia, functional asplenia or any condition resulting in the absence or removal o the spleen
• Guillain-Barre Syndrome
• Women subjects with positive urinary pregnancy test
• Any history of immunosuppressive medications or cytotoxic medications or inhaled corticosteroids within the past six months (with the exception of corticosteroid nasal spray for allergic rhinitis or topical corticosteroids for an acute uncomplicated dermatitis)
• History of any blood products administration within 3 months before the dosing
• Administration of any other investigational research agents within 30 days before the dosing
• Administration of any live attenuated vaccine within 30 days before the dosing
• Administration of subunit or inactivated vaccines, e.g. pneumococcal vaccine, or allergy treatment with antigen injections, within 14 days before the dosing
• Be receiving anti-TB prophylaxis or therapy currently
• Axillary temperature >37.0 centigrade at the time of dosing
• Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder requiring therapy that has not been well controlled on medication for the past two years; disorder requiring lithium; or suicidal ideation occurring within five years prior to enrollment
• Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1: 10 ug, 14 days	Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 14 days apart: 5 microgram per dose; Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 28 days apart: 5 microgram per dose; Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 28 days apart: 10 microgram per dose; Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 28 days apart: 15 microgram per dose
Experimental: 2: 5 ug, 28 days	Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 14 days apart: 5 microgram per dose; Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 28 days apart: 5 microgram per dose; Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 28 days apart: 10 microgram per dose; Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 28 days apart: 15 microgram per dose
Experimental: 3: 10 ug, 28 days	Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 14 days apart: 5 microgram per dose; Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 28 days apart: 5 microgram per dose; Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 28 days apart: 10 microgram per dose; Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 28 days apart: 15 microgram per dose
Experimental: 4: 15 ug, 28days	Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 14 days apart: 5 microgram per dose; Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 28 days apart: 5 microgram per dose; Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 28 days apart: 10 microgram per dose; Biological: pandemic influenza vaccine (H5N1 strain NIBRG-14); two-dose regimen with 28 days apart: 15 microgram per dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
HI antibody and Neutralization antibody	0,28,42,56

Secondary Outcome Measures

Outcome Measure	Time Frame
adverse reactions	0,28,42,56

Collaborators and Investigators

• Sponsor: Sinovac Biotech Co., Ltd
• Collaborators: Centers for Disease Control and Prevention, China
• Investigators: Principal Investigator: Jiang Wu, Beijing Centers for Diseases Control and Prevention

Publications and helpful links

General Publications

• Wu J, Fang HH, Chen JT, Zhou JC, Feng ZJ, Li CG, Qiu YZ, Liu Y, Lu M, Liu LY, Dong SS, Gao Q, Zhang XM, Wang N, Yin WD, Dong XP. Immunogenicity, safety, and cross-reactivity of an inactivated, adjuvanted, prototype pandemic influenza (H5N1) vaccine: a phase II, double-blind, randomized trial. Clin Infect Dis. 2009 Apr 15;48(8):1087-95. doi: 10.1086/597401.

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: September 24, 2007
• First Submitted That Met QC Criteria: September 24, 2007
• First Posted (Estimate): September 26, 2007

Study Record Updates

• Last Update Posted (Estimate): November 9, 2007
• Last Update Submitted That Met QC Criteria: November 8, 2007
• Last Verified: November 1, 2007

More Information

Terms related to this study

• 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: PRO-PanFlu-2001