Clinical trial NCT00814229: Safety and Immunogenicity of Influenza H9 Vaccine in Humans
Official title: Randomised Dose Ranging Observer Blind Single Centre Study to Evaluate Safety and Immunogenicity of Adjuvanted and Non-adjuvanted Influenza H9 Influenza Vaccine in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza
Keywords: influenza
H9N2
vaccine
Lead sponsor: University Hospitals, Leicester
Sponsor class: OTHER
Collaborators: name: Crucell Holland BV
name: National Institute of Biological Standards and Control
name: Public Health England
First posted: 2008-12-24
Enrollment: 353
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: H9N2 influenza circulates in animal and poultry and has caused delf limiting infections in children. Influenza H9N2 poses a pandemic threat to humans.

This study evaluates the safety and immunogenicity of adjuvanted and non-adjuvanted whole virus and virosomal H9N2 vaccines by the intramuscular route. We also assess intradermal route of administration to see if this has any advantages. The aim is to assess antibody responses before and after vaccination. The hypothesis is that lower doses of adjuvanted vaccine will induce similar antibody responses to non-adjuvanted vaccine

Detailed description: A double-blind, single centre comparative study in which fourteen groups of 40 male and female adults \>18 years of age will be randomly allocated to receive 1.7, 5, 15 or 45 µg quantities of whole virion (WV), Aluminium -adjuvanted WV(Al-WV), and virosomal (V) influenza A/Hong Kong/1073/99 (H9N2) vaccines by intramuscular injection into the deltoid muscle; or 5 or 15microg WV vaccine administered by intradermal injection. A second dose of the same vaccine containing the same quantity of antigen as in the first dose will be administered 21 days later. Subjects will be observed for local and systemic reactions for 30 minutes after each immunisation (day 0 and 21), and will be monitored for any reactions and other adverse events for 7 days after immunisation. Blood for immunogenicity studies will be obtained at day 0 (pre-immunisation), day-21 (+4 days), and at day-42 (i.e., 21 +4 days after the second immunization). Immunogenicity will be evaluated by haemagglutination inhibition, virus neutralization,, single radial haemolysis, neuraminidase inhibition and cellular mediated responses (in a subset of 5-10 subjects from each group).

Eligibility criteria: Inclusion Criteria:

* Mentally competent adults, who have signed an informed consent form after having received a detailed explanation of the study protocol.
* Male or female subjects over 18 years who are either healthy or have a stable medical condition.
* Able to understand and comply with all study procedures and to complete study diaries
* Individuals who can be contacted throughout the study and are available for all study visits
* Females should either be using secure contraceptive precautions including a) the oral contraceptive pill, b) condom/barrier contraception c) partner has had a vasectomy, d) be surgically sterilised, or e) post- (defined as at least two years since the last menstrual period)

Exclusion Criteria:

* Any clinically significant concurrent illness or unstable medical condition including: malignant tumours, autoimmune illnesses (including rheumatoid arthritis), acute or progressive renal or hepatic pathology, chronic obstructive pulmonary disease requiring oxygen therapy, and any active neurological disorder.
* Individuals with a history of anaphylaxis or serious reactions to vaccines; hypersensitivity to eggs, chicken protein, chicken feathers, influenzal viral protein, neomycin or polymixin, or products containing mercury.
* Persons with known immunosuppressive disease or who use systemic immunosuppressive drugs or other drugs listed in section 8 of the British National Formulary (BNF) or chloroquine, gold or penicillamine or other drugs listed in section 10.1.3 of the BNF to suppress a chronic disease process, or have received in the last 6 months radiotherapy or chemotherapy.
* Subjects who are at high risk of developing illnesses of the immune system.
* Individuals who are taking immunostimulant therapy or interferon
* Individuals who have received blood products or immunoglobulins parenterally during the preceding three months.
* Women should not be pregnant or lactating.
* Women who refuse to use a reliable contraceptive method throughout the study
* Known or suspected drug abuse.
* Individuals who have received another vaccine or experimental (investigational) drug in the preceding 4 weeks.
* Individuals who have previously received H9N2 vaccine
* Unable to lead an independent life either physically or mentally
* Regularly drink more than 40 units of alcohol weekly
* Individuals who have had acute respiratory pathology or infections requiring systemic antibiotic or antiviral therapy during the preceding 7 days (chronic antibiotic therapy for prevention of urinary tract infections is acceptable).
* Individuals who had a temperature over 38 degrees C in the preceding 3 days.
* Individuals who, in the opinion of the investigator, have conditions that might complicate interpretation of the study results.

Primary outcomes:
measure: Geometric mean antibody titres of antibody to influenza H9 by HI and neutralising antibody assays
timeFrame: Pre vaccination, 21 days and 42 days
Secondary outcomes:
measure: Local and systemic reactogenicity of influenza H9 vaccine
timeFrame: within 7 days of vaccination
measure: seroprotective antibody titres to influenza H9 by HI and neutralising antibody
timeFrame: pre vacciantion, 21 and 42 days post-vaccine
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: University Hospitals Leicester
state: Leicestershire
Study officials:
affiliation: University of Leicester
name: Karl G Nicholson, FRCP, MD
role: PRINCIPAL_INVESTIGATOR
References: