Novel Influenza A/H1N1 Split- Virion Vaccine in Healthy Population Aged 3 Years and Older

Sponsor

Jiangsu Province Centers for Disease Control and Prevention (Other)

Overall Status

Completed

CT.gov ID

NCT00975572

Collaborator

Hualan Biological Bacterin Co. Ltd. (Industry)

2,200

Enrollment

Location

Arms

7.1

Duration (Months)

311.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary safety objective of this study is to assess the safety of split- virion inactivated H1N1 vaccine with and without adjuvant when administered at the 7.5,15 or 30 mcg dose. The primary immunogenicity objective is to assess the antibody response following each dose of split- virion inactivated A(H1N1) vaccine with and without adjuvant. Participants will include up to 2200 healthy persons age 3 and older who have no history of novel influenza H1N1 2009 infection or novel influenza H1N1 2009 vaccination. This is a randomized, double-blinded, Phase II study in healthy males and non-pregnant females, aged 3 years and older. Subjects will be stratified by elders (equal to or more than 61 years), adults (18-60 years), adolescents (12-17 years) and children (3-11 years), elders and adolescents will be randomized into 5 dose groups (adjuvanted H1N1 vaccine of 7.5,15 or 30 mcg per dose or non-adjuvanted H1N1 vaccine of 15 or 30 mcg per dose), children will be randomized into 4 dose groups (adjuvanted H1N1 vaccine of 7.5 or 15 mcg per dose or non-adjuvanted H1N1 vaccine of 15 or 30 mcg per dose), adults will be randomized into 6 dose groups (adjuvanted H1N1 vaccine of 7.5,15 or 30 mcg per dose or non-adjuvanted H1N1 vaccine of 15 or 30 mcg per dose or placebo), 110 subjects per dose and age stratum will be to receive intramuscular influenza H1N1 vaccine. The H1N1 vaccine will be administered at Day 0 and Day 21. Following immunization, safety will be measured by assessment of adverse events through 21 days following the last vaccination (Day 42 for those receiving both doses), serious adverse events and new-onset chronic medical conditions through 6 months post the final vaccination (Day 180 after second vaccination), and reactogenicity to the vaccine for 8 days (Day 0-7) following each vaccination. Immunogenicity testing will be hemagglutination inhibiting (HAI) on serum obtained on the day 21 of each vaccination (prior to vaccination), on Day 21 after first vaccination, and 21 days following the second vaccination (Day 42).

Condition or Disease	Intervention/Treatment	Phase
Virus Diseases Respiratory Tract Diseases Respiratory Tract Infections Influenza Orthomyxoviridae Infections	Biological: split-virion, non-adjuvanted H1N1 vaccine of 30 μg Biological: Experimental: split-virion, adjuvanted H1N1 vaccine of 7.5 μg Biological: Experimental: split-virion, adjuvanted H1N1 vaccine of 15 μg Biological: Experimental: split-virion, adjuvanted H1N1 vaccine of 30 μg Biological: Experimental: split-virion, non-adjuvanted H1N1 vaccine of 15 μg Biological: Placebo Comparator: Placebo control	Phase 2

Detailed Description

Recently, a novel swine-origin influenza A/H1N1 virus was identified as a significant cause of febrile respiratory illnesses in Mexico and the United States. It rapidly spread to many countries around the world, prompting the World Health Organization (WHO) to declare a pandemic on June 11, 2009. Data from several cohorts in different age groups that received licensed trivalent seasonal influenza vaccines suggest that these vaccines are unlikely to provide protection against the new virus. In addition, adults are more likely to have measurable levels of serum hemagglutination inhibition assay (HAI) or neutralizing antibody than are children. These data indicate the need to develop vaccines against the new H1N1 strain and suggest that different vaccine strategies (e.g., number of doses, need for adjuvant) may be appropriate for persons in different age groups. The primary safety objective of this study is to assess the safety of split- virion inactivated H1N1 vaccine with and without adjuvant when administered at the 7.5,15 or 30 mcg dose. The primary immunogenicity objective is to assess the antibody response following each dose of split- virion inactivated A(H1N1) vaccine with and without adjuvant,. Participants will include up to 2200 healthy persons age 3 and older who have no history of novel influenza H1N1 2009 infection or novel influenza H1N1 2009 vaccination. This is a randomized, double-blinded, Phase II study in healthy males and non-pregnant females, aged 3 years and older. This study is designed to investigate the safety, reactogenicity, and immunogenicity of an inactivated influenza H1N1 virus vaccine at different dose levels of split- virion inactivated H1N1 vaccine with or without adjuvant or placebo in 4 aged groups. Subjects will be stratified by elders (equal to or more than 61 years), adults (18-60 years), adolescents (12-17 years) and children (3-11 years), elders and adolescents will be randomized into 5 dose groups(adjuvanted H1N1 vaccine of 7.5,15 or 30 mcg per dose or non-adjuvanted H1N1 vaccine of 15 or 30 mcg per dose ) , children will be randomized into 4 dose groups(adjuvanted H1N1 vaccine of 7.5 or 15 mcg per dose or non-adjuvanted H1N1 vaccine of 15 or 30 mcg per dose ), adults will be randomized into 6 dose groups(adjuvanted H1N1 vaccine of 7.5,15 or 30 mcg per dose or non-adjuvanted H1N1 vaccine of 15 or 30 mcg per dose or placebo ), 110 subjects per dose and age stratum will be to receive intramuscular influenza H1N1 vaccine . The H1N1 vaccine will be administered at Day 0 and Day 21. Following immunization, safety will be measured by assessment of adverse events through 21 days following the last vaccination (Day 42 for those receiving both doses), serious adverse events and new-onset chronic medical conditions through 6 months post the final vaccination (Day 180 after second vaccination), and reactogenicity to the vaccine for 8 days (Day 0-7) following each vaccination. Immunogenicity testing will be HAI on serum obtained on the day 21 of each vaccination (prior to vaccination), on Day 21 after first vaccination, and 21 days following the second vaccination (Day 42).

Study Design

Study Type:

Interventional

Actual Enrollment :

2200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

A Double-blind, Randomized, Stratified and Controlled Clinical Trial With Split-virion, Adjuvanted and Non-adjuvanted Influenza A/H1N1 Vaccines in Healthy Adults, Elders, Adolescents and Children

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

Sep 1, 2009

Actual Study Completion Date :

Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: split-virion, adjuvanted H1N1 vaccine of 7.5 μg	Biological: Experimental: split-virion, adjuvanted H1N1 vaccine of 7.5 μg 440 participants (110 elders,110 adults, 110 adolescents and 110 children) to receive split-virion, adjuvanted H1N1 vaccine of 7.5 μg on day 0 and 21.
Experimental: split-virion, adjuvanted H1N1 vaccine of 15 μg	Biological: Experimental: split-virion, adjuvanted H1N1 vaccine of 15 μg 440 participants (110 elders, 110 adults, 110 adolescents and 110 children) to receive split-virion, adjuvanted H1N1 vaccine of 15 μg on day 0 and 21.
Experimental: split-virion, adjuvanted H1N1 vaccine of 30 μg	Biological: Experimental: split-virion, adjuvanted H1N1 vaccine of 30 μg 330 participants (110 elders, 110 adults, and 110 adolescents) to receive split-virion, adjuvanted H1N1 vaccine of 30 μg on day 0 and 21.
Experimental: split-virion, non-adjuvanted H1N1 vaccine of 15 μg	Biological: Experimental: split-virion, non-adjuvanted H1N1 vaccine of 15 μg 440 participants (110 elders, 110 adults, 110 adolescents and 110 children) to receive split-virion, non-adjuvanted H1N1 vaccine of 15 μg on day 0 and 21.
Placebo Comparator: Placebo control	Biological: Placebo Comparator: Placebo control 110 adults to receive placebo control (Phosphate Buffer Saline) on day 0 and 21.
Experimental: split-virion, non-adjuvanted H1N1 vaccine of 30 μg	Biological: split-virion, non-adjuvanted H1N1 vaccine of 30 μg 440 participants (110 elders, 110 adults, 110 adolescents and 110 children) to receive split-virion, non-adjuvanted H1N1 vaccine of 30 μg on day 0 and 21.

Outcome Measures

Primary Outcome Measures

Hemagglutination inhibition antibody titer [D0,D21,D35]

Secondary Outcome Measures

local and systemic adverse reaction after vaccination [D0-42]

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy male or female aged 3 and older
Be able to show legal identity card for the sake of recruitment
Volunteers or their guardians are able to understand and sign the informed consent

Exclusion Criteria:

Cases, cured cases and close contact of influenza A (H1N1) virus
Women of pregnancy, lactation or about to be pregnant in 60 days
Subject that has a medical history of any of the following: allergic history, or allergic to any ingredient of vaccine, such as egg, egg protein, etc
Serious 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
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:

Febrile seizures under the age of two years old
Seizures secondary to alcohol withdrawal more than 3 years ago, or
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
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 or seasonal influenza vaccine 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
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