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

Influenza Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00975572
• Other study ID #: JSVCT001
• Status: Completed
• Phase: Phase 2
• First received: September 8, 2009
• Last updated: September 11, 2012
• Start date: July 2009
• Est. completion date: February 2010

Study information

• Verified date: September 2009
• Source: Jiangsu Province Centers for Disease Control and Prevention
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2200
• Est. completion date: February 2010
• Est. primary completion date: September 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 3 Years to 90 Years

Eligibility

Inclusion Criteria:

1. Healthy male or female aged 3 and older

2. Be able to show legal identity card for the sake of recruitment

3. Volunteers or their guardians are able to understand and sign the informed consent

Exclusion Criteria:

1. Cases, cured cases and close contact of influenza A (H1N1) virus

2. Women of pregnancy, lactation or about to be pregnant in 60 days

3. 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

4. Serious adverse reactions to vaccines such as anaphylaxis, hives, respiratory difficulty, angioedema, or abdominal pain

5. Autoimmune disease or immunodeficiency

6. 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

7. Diabetes mellitus (type I or II), with the exception of gestational diabetes

8. History of thyroidectomy or thyroid disease that required medication within the past 12 months

9. Serious angioedema episodes within the previous 3 years or requiring medication in the previous two years

10. 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

11. 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

12. 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

13. Asplenia, functional asplenia or any condition resulting in the absence or removal o the spleen

14. Guillain-Barre Syndrome

15. 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)

16. History of any blood products or seasonal influenza vaccine administration within 3 months before the dosing

17. Administration of any other investigational research agents within 30 days before the dosing

18. Administration of any live attenuated vaccine within 30 days before the dosing

19. Administration of subunit or inactivated vaccines, e.g., pneumococcal vaccine, or allergy treatment with antigen injections, within 14 days before the dosing

20. Be receiving anti-TB prophylaxis or therapy currently

21. Axillary temperature > 37.0 centigrade at the time of dosing

22. 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

23. 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 Design

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

Related Conditions & MeSH terms

• Infection
• Influenza
• Influenza, Human
• Orthomyxoviridae Infections
• Respiratory Tract Diseases
• Respiratory Tract Infections
• Virus Diseases

Intervention

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.
• 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
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
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
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
110 adults to receive placebo control (Phosphate Buffer Saline) on day 0 and 21.

Locations

Country	Name	City	State
China	Taizhou Municipal Center for Disease Control and Prevention	Taizhou	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
Jiangsu Province Centers for Disease Control and Prevention	Hualan Biological Bacterin Co. Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hemagglutination inhibition antibody titer		D0,D21,D35	No
Secondary	local and systemic adverse reaction after vaccination		D0-42	Yes