Clinical trial NCT00868218: Study of a Parenterally Administered H5N1 Influenza Vaccine in Healthy Adults
Official title: Preparing for an Influenza Pandemic: A Phase I Study of a Parenterally Administered H5N1 Influenza Vaccine in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza
Healthy
Keywords: Influenza A
pandemic
vaccine
immunogenicity
Virus
H5N1
Lead sponsor: University of Bergen
Sponsor class: OTHER
Collaborators: name: Haukeland University Hospital
name: European Commission
First posted: 2009-03-24
Enrollment: 60
Sex: ALL
Minimum age (years): 19
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

Brief summary: The safety and tolerability of the pandemic A/H5N1 virosomal vaccine formulated with or without the 3rd generation ISCOM™ adjuvant for parenteral administration will be investigated locally and systemically and by using haematological, biochemical and immunological screening tests. The immunogenicity of the H5N1 vaccine will be assessed through the induction of local and systemic antibody and cellular immune responses. In a pandemic situation, an important aspect is the rapidity of the immune response to the H5N1 vaccine so the detailed kinetics of the immune response will be investigated. The capacity of the vaccine to elicit long lasting immunity and cross reactive immunity to H5 viruses will also be evaluated. Furthermore, the quality of the immune response induced by the vaccine will be studied. The vaccine will be administered as twice the normal human dose (30μg HA) with and without adjuvant, and in a dose sparing manor of half (7.5μg HA) and one tenth (1.5μg HA) of the normal human dose with adjuvant. Sixty subjects will receive two doses of virosomal H5N1 influenza vaccine (separated by 21 ± 4 days) by intramuscular injection into the deltoid muscle. Escalating doses will be separated by a period of one week. Four groups each containing 15 subjects will receive two doses of the pandemic virosomal A/H5N1 influenza vaccine containing:

Group 1 30µg HA IM, Group 2 1.5µg HA adjuvanted with 50µg 3rd generation ISCOM™ IM, Group 3 7.5µg HA adjuvanted with 50µg 3rd generation ISCOM™ IM, Group 4 30µg HA adjuvanted with 50µg 3rd generation ISCOM™ IM.


Eligibility criteria: Inclusion Criteria:

* Healthy volunteers (as concluded from the medical history, physical examination, and clinical judgment) aged 19 to 50 years old
* Females using a reliable method of contraception (from 4 weeks prior to the first vaccination until 4 weeks after the second vaccination) and a negative urine pregnancy test will be required before administration of each dose of vaccine
* Signed informed consent
* Subjects able to understand and comply with the study protocol and complete the Adverse Event Form
* Subjects able to attend the scheduled visits
* Subjects with normal pre-screening values. If a subjects prescreening samples lie outside the reference values he/she will only be included in the study based upon the medical evaluation of the clinical investigator

Exclusion Criteria:

* Persons with a history of anaphylaxis or serious reactions to any vaccine
* Persons with known hypersensitivity to any of the vaccine components
* Persons who have had a temperature \>38oC during the previous 72 hours
* Persons who have had an acute respiratory infection during the last 7 days
* Women who are pregnant or breast-feeding
* Persons with chronic illness at any stage that could interfere with trial conduct or compliance
* Persons who have received blood products or immunoglobulins parenterally during the previous 3 months
* Persons who have been vaccinated with any vaccine during the 4 weeks preceding the first trial vaccination
* Persons with known or suspected immunosuppressive disease or who use systemic immunosuppressive drugs
* Persons taking immunostimulant therapy
* Persons involved in another clinical trial during the last month.
* Suspected non-compliance

Primary outcomes:
measure: Solicted Adverse Events
timeFrame: three months
measure: Adverse Events
timeFrame: 42 days
Secondary outcomes:
measure: Immunogenicity of a Non-adjuvanted and 3rd Generation ISCOM™ Adjuvanted Virosomal H5N1 Influenza Vaccine
timeFrame: one year
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland Univeristy Hospital
Study officials:
affiliation: Haukeland Univeristy Hospital
name: Haakon Sjursen, MD
role: STUDY_DIRECTOR
References:
citation: Pedersen GK, Madhun AS, Breakwell L, Hoschler K, Sjursen H, Pathirana RD, Goudsmit J, Cox RJ. T-helper 1 cells elicited by H5N1 vaccination predict seroprotection. J Infect Dis. 2012 Jul 15;206(2):158-66. doi: 10.1093/infdis/jis330. Epub 2012 May 2.
citation: Cox RJ, Pedersen G, Madhun AS, Svindland S, Saevik M, Breakwell L, Hoschler K, Willemsen M, Campitelli L, Nostbakken JK, Weverling GJ, Klap J, McCullough KC, Zambon M, Kompier R, Sjursen H. Evaluation of a virosomal H5N1 vaccine formulated with Matrix M adjuvant in a phase I clinical trial. Vaccine. 2011 Oct 19;29(45):8049-59. doi: 10.1016/j.vaccine.2011.08.042. Epub 2011 Aug 22.
citation: Pedersen GK, Sjursen H, Nostbakken JK, Jul-Larsen A, Hoschler K, Cox RJ. Matrix M(TM) adjuvanted virosomal H5N1 vaccine induces balanced Th1/Th2 CD4(+) T cell responses in man. Hum Vaccin Immunother. 2014;10(8):2408-16. doi: 10.4161/hv.29583.
citation: Pedersen GK, Hoschler K, Oie Solbak SM, Bredholt G, Pathirana RD, Afsar A, Breakwell L, Nostbakken JK, Raae AJ, Brokstad KA, Sjursen H, Zambon M, Cox RJ. Serum IgG titres, but not avidity, correlates with neutralizing antibody response after H5N1 vaccination. Vaccine. 2014 Jul 31;32(35):4550-4557. doi: 10.1016/j.vaccine.2014.06.009. Epub 2014 Jun 18.
citation: Cox RJ, Major D, Pedersen G, Pathirana RD, Hoschler K, Guilfoyle K, Roseby S, Bredholt G, Assmus J, Breakwell L, Campitelli L, Sjursen H. Matrix M H5N1 Vaccine Induces Cross-H5 Clade Humoral Immune Responses in a Randomized Clinical Trial and Provides Protection from Highly Pathogenic Influenza Challenge in Ferrets. PLoS One. 2015 Jul 6;10(7):e0131652. doi: 10.1371/journal.pone.0131652. eCollection 2015.
citation: Nachbagauer R, Wohlbold TJ, Hirsh A, Hai R, Sjursen H, Palese P, Cox RJ, Krammer F. Induction of broadly reactive anti-hemagglutinin stalk antibodies by an H5N1 vaccine in humans. J Virol. 2014 Nov;88(22):13260-8. doi: 10.1128/JVI.02133-14. Epub 2014 Sep 10.