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Safety and Immunogenicity of Influenza H9 Vaccine in Humans

This study has been completed.
Sponsor:
Collaborators:
Crucell Holland BV
National Institute of Biological Standards and Control
Health Protection Agency, United Kingdom
Information provided by:
University Hospitals, Leicester
ClinicalTrials.gov Identifier:
NCT00814229
First received: December 23, 2008
Last updated: July 20, 2009
Last verified: July 2009
  Purpose

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


Condition Intervention Phase
Influenza
Biological: H9N2 whole virus vaccine, IM, 1.5microg
Biological: H9N2 whole virus vaccine, IM, 5microg
Biological: H9N2 whole virus vaccine vaccine, IM, 15microg
Biological: H9N2 whole virus vaccine, IM, 45microg
Biological: H9N2 whole virus vaccine, alum, IM, 1.5microg
Biological: H9N2 whole virus, alum, IM, 5microg
Biological: H9N2 vaccine, whole virus, alum, IM, 15 microg
Biological: H9N2 vaccine, whole virus, alum, IM, 45microg
Biological: H9N2 virosome vaccine, IM, 1.5microg
Biological: H9N2 virosomal vaccine, IM, 5microg
Biological: H9N2 virosomal vaccine, IM, 15microg
Biological: H9N2 virosomal vaccine, IM, 45microg
Biological: H9N2 whole virus vaccine, ID, 5microg
Biological: H9N2 whole virus vaccine, ID, 15microg
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by University Hospitals, Leicester:

Primary Outcome Measures:
  • Geometric mean antibody titres of antibody to influenza H9 by HI and neutralising antibody assays [ Time Frame: Pre vaccination, 21 days and 42 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Local and systemic reactogenicity of influenza H9 vaccine [ Time Frame: within 7 days of vaccination ] [ Designated as safety issue: Yes ]
  • seroprotective antibody titres to influenza H9 by HI and neutralising antibody [ Time Frame: pre vacciantion, 21 and 42 days post-vaccine ] [ Designated as safety issue: No ]

Enrollment: 353
Study Start Date: August 2007
Study Completion Date: September 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Vaccine 1
influenza H9N2 vaccine whole virus containing 1.5microg haemagglutinin by intramuscular injection
Biological: H9N2 whole virus vaccine, IM, 1.5microg
influenza H9N2 vaccine whole virus containing 1.5microg haemagglutinin by intramuscular injection
Active Comparator: vaccine 2
influenza H9N2 vaccine whole virus containing 5microg haemagglutinin by intramuscular injection
Biological: H9N2 whole virus vaccine, IM, 5microg
influenza H9N2 vaccine whole virus containing 5microg haemagglutinin by intramuscular injection
Active Comparator: Vaccine 3
influenza H9N2 vaccine whole virus containing 15microg haemagglutinin by intramuscular injection
Biological: H9N2 whole virus vaccine vaccine, IM, 15microg
influenza H9N2 vaccine whole virus containing 15microg haemagglutinin by intramuscular injection
Active Comparator: Vaccine 4
influenza H9N2 vaccine whole virus containing 45microg haemagglutinin by intramuscular injection
Biological: H9N2 whole virus vaccine, IM, 45microg
influenza H9N2 vaccine whole virus containing 45microg haemagglutinin by intramuscular injection
Active Comparator: Vaccine 5
influenza H9N2 vaccine whole virus adjuvanted with alum hydroxide containing 1.5microg haemagglutinin by intramuscular injection
Biological: H9N2 whole virus vaccine, alum, IM, 1.5microg
influenza H9N2 vaccine whole virus adjuvanted with alum hydroxide containing 1.5microg haemagglutinin by intramuscular injection
Active Comparator: Vaccine 6
influenza H9N2 vaccine whole virus adjuvanted with alum hydroxide containing 5microg haemagglutinin by intramuscular injection
Biological: H9N2 whole virus, alum, IM, 5microg
influenza H9N2 vaccine whole virus adjuvanted with alum hydroxide containing 5microg haemagglutinin by intramuscular injection
Active Comparator: Vaccine 7
influenza H9N2 vaccine whole virus adjuvanted with alum hydroxide containing 15microg haemagglutinin by intramuscular injection
Biological: H9N2 vaccine, whole virus, alum, IM, 15 microg
influenza H9N2 vaccine whole virus adjuvanted with alum hydroxide containing 15microg haemagglutinin by intramuscular injection
Active Comparator: Vaccine 8
influenza H9N2 vaccine whole virus adjuvanted with alum hydroxide containing 45microg haemagglutinin by intramuscular injection
Biological: H9N2 vaccine, whole virus, alum, IM, 45microg
influenza H9N2 vaccine whole virus adjuvanted with alum hydroxide containing 45microg haemagglutinin by intramuscular injection
Active Comparator: Vaccine 9
influenza H9N2 vaccine virosomal containing 1.5microg haemagglutinin by intramuscular injection
Biological: H9N2 virosome vaccine, IM, 1.5microg
influenza H9N2 vaccine virosomal containing 1.5microg haemagglutinin by intramuscular injection
Active Comparator: Vaccine 10
influenza H9N2 vaccine virosomal containing 5microg haemagglutinin by intramuscular injection
Biological: H9N2 virosomal vaccine, IM, 5microg
influenza H9N2 vaccine virosome containing 5microg haemagglutinin by intramuscular injection
Active Comparator: Vaccine 11
influenza H9N2 vaccine virosomal containing 15microg haemagglutinin by intramuscular injection
Biological: H9N2 virosomal vaccine, IM, 15microg
influenza H9N2 vaccine virosome containing 15microg haemagglutinin by intramuscular injection
Active Comparator: Vaccine 12
influenza H9N2 vaccine virosomal containing 45microg haemagglutinin by intramuscular injection
Biological: H9N2 virosomal vaccine, IM, 45microg
influenza H9N2 vaccine virosome containing 45microg haemagglutinin by intramuscular injection
Active Comparator: Vaccine 13
influenza H9N2 vaccine whole virus containing 5microg haemagglutinin by intradermal injection
Biological: H9N2 whole virus vaccine, ID, 5microg
influenza H9N2 vaccine whole virus containing 5microg haemagglutinin by intradermal injection
Active Comparator: Vaccine 14
influenza H9N2 vaccine whole virus containing 15microg haemagglutinin by intradermal injection
Biological: H9N2 whole virus vaccine, ID, 15microg
influenza H9N2 vaccine whole virus containing 15microg haemagglutinin by intradermal injection

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00814229

Locations
United Kingdom
University Hospitals Leicester
Leicester, Leicestershire, United Kingdom, LE1 5WW
Sponsors and Collaborators
University Hospitals, Leicester
Crucell Holland BV
National Institute of Biological Standards and Control
Health Protection Agency, United Kingdom
Investigators
Principal Investigator: Karl G Nicholson, FRCP, MD University of Leicester
  More Information

No publications provided

Responsible Party: Profressor Karl Nicholson, University of Leicester
ClinicalTrials.gov Identifier: NCT00814229     History of Changes
Other Study ID Numbers: UHL 08162, REC 6794
Study First Received: December 23, 2008
Last Updated: July 20, 2009
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University Hospitals, Leicester:
influenza
H9N2
vaccine

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Respiratory Tract Diseases
Respiratory Tract Infections
Virus Diseases
Hemagglutinins
Agglutinins
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 27, 2014