Studies of Pandemic Influenza (H1N1) 2009 Vaccine in Bergen (H1N1VAC)

• ClinicalTrials.gov Identifier: NCT01003288
• Recruitment Status: Completed
• First Posted: October 28, 2009
• Results First Posted: August 24, 2016
• Last Update Posted: November 18, 2019
• Sponsor: University of Bergen
• Collaborator: Haukeland University Hospital
• Information provided by (Responsible Party): Rebecca Cox, University of Bergen

Tracking Information

• First Submitted Date: October 27, 2009
• First Posted Date: October 28, 2009
• Results First Submitted Date: June 6, 2015
• Results First Posted Date: August 24, 2016
• Last Update Posted Date: November 18, 2019
• Study Start Date: October 2009
• Actual Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 19, 2016)

Number of Participants With Local and Systemic Adverse Events [ Time Frame: 21 days after vaccination ]

Solicited adverse events were collected on side reactions form which were filled in for 21 days after pandemic or seasonal vaccination.

• Original Primary Outcome Measures (submitted: October 27, 2009): The primary endpoints of the trial are the local and systemic adverse events and tolerability of parenterally administered adjuvanted H1N1 influenza vaccine in all volunteers [ Time Frame: 2010 ]
• Change History: Complete list of historical versions of study NCT01003288 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: September 19, 2016)

Number of Participants With Immunogenicity as Determined Using Haemagglutination Inhibition Assay [ Time Frame: 7, 14, 21 days post vaccination and long term follow up for 5 years ]

Antibody responses were measured using the HI assay to evaluate the rapidity and long term duration of the response

• Original Secondary Outcome Measures (submitted: October 27, 2009): The secondary endpoints are the evaluation of the immunogenicity of adjuvanted H1N1 influenza vaccine and the ability of the vaccine to meet the CHMP evaluation criteria in a subset of volunteers [ Time Frame: 2011 ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Studies of Pandemic Influenza (H1N1) 2009 Vaccine in Bergen
• Official Title: Safety and Immunogenicity Studies of Pandemic Influenza (H1N1) 2009 Vaccine in Bergen
• Brief Summary: Haukeland University Hospital has approximately 8000 employees many of whom will be in the front line to receive the pandemic A/H1N1 vaccine. We propose to conduct a safety and immunogenicity study in these subjects

Detailed Description

The investigators will conduct a safety and immunogenicity study in health employees as detailed below:

• Examine adverse events of all employees after vaccination using adverse events form
• Examine the immunogenicity of the vaccine by collecting blood samples at days 0, 21 & 42 after vaccination (up to 500 people)
• Provide a detailed time course of the immune response to vaccination with a novel influenza H1N1 virus including the kinetics of the T-cell, B-cell and antibody responses in 50 volunteers
• Investigate the long lasting immunity induced by the vaccine
• Examine the ability of the vaccine to induce cross-reactive immunity to H1N1 strains.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Healthy

Intervention

Biological: Adjuvanted influenza H1N1split virion vaccine

Vaccination Pandemrix suspension and emulsion for emulsion for injection. 1 dose (0.5 ml) contains Split influenza virus, inactivated, containing antigen 3.75 micrograms of A/California/7/2009 (H1N1)v-like strain (X-179A)

* Pandemic influenza vaccine (H1N1)v (split virion, inactivated, adjuvanted)

Other Name: Pandemrix

Study Arms

Experimental: Pandemic influenza H1N1 vaccine

Influenza vaccine

Intervention: Biological: Adjuvanted influenza H1N1split virion vaccine

Publications *

• Madhun AS, Akselsen PE, Sjursen H, Pedersen G, Svindland S, Nøstbakken JK, Nilsen M, Mohn K, Jul-Larsen A, Smith I, Major D, Wood J, Cox RJ. An adjuvanted pandemic influenza H1N1 vaccine provides early and long term protection in health care workers. Vaccine. 2010 Dec 16;29(2):266-73. doi: 10.1016/j.vaccine.2010.10.038. Epub 2010 Oct 27.
• Pedersen G, Halstensen A, Sjursen H, Naess A, Kristoffersen EK, Cox RJ. Pandemic influenza vaccination elicits influenza-specific CD4+ Th1-cell responses in hypogammaglobulinaemic patients: four case reports. Scand J Immunol. 2011 Aug;74(2):210-8. doi: 10.1111/j.1365-3083.2011.02561.x.
• Jul-Larsen Å, Madhun AS, Brokstad KA, Montomoli E, Yusibov V, Cox RJ. The human potential of a recombinant pandemic influenza vaccine produced in tobacco plants. Hum Vaccin Immunother. 2012 May;8(5):653-61. doi: 10.4161/hv.19503. Epub 2012 May 1.
• Pathirana RD, Bredholt G, Akselsen PE, Pedersen GK, Cox RJ. A(H1N1)pdm09 vaccination of health care workers: improved immune responses in low responders following revaccination. J Infect Dis. 2012 Dec 1;206(11):1660-9. doi: 10.1093/infdis/jis589. Epub 2012 Sep 11.
• Lartey S, Pathirana RD, Zhou F, Jul-Larsen Å, Montomoli E, Wood J, Cox RJ. Single dose vaccination of the ASO3-adjuvanted A(H1N1)pdm09 monovalent vaccine in health care workers elicits homologous and cross-reactive cellular and humoral responses to H1N1 strains. Hum Vaccin Immunother. 2015;11(7):1654-62. doi: 10.1080/21645515.2015.1048939.
• Eidem S, Tete SM, Jul-Larsen Å, Hoschler K, Montomoli E, Brokstad KA, Cox RJ. Persistence and avidity maturation of antibodies to A(H1N1)pdm09 in healthcare workers following repeated annual vaccinations. Vaccine. 2015 Aug 7;33(33):4146-54. doi: 10.1016/j.vaccine.2015.05.081. Epub 2015 Jun 7.
• Trieu MC, Zhou F, Lartey SL, Sridhar S, Mjaaland S, Cox RJ. Augmented CD4(+) T-cell and humoral responses after repeated annual influenza vaccination with the same vaccine component A/H1N1pdm09 over 5 years. NPJ Vaccines. 2018 Aug 14;3:37. doi: 10.1038/s41541-018-0069-1. eCollection 2018. Erratum in: NPJ Vaccines. 2018 Sep 11;3:45.
• Trieu MC, Zhou F, Lartey S, Jul-Larsen Å, Mjaaland S, Sridhar S, Cox RJ. Long-term Maintenance of the Influenza-Specific Cross-Reactive Memory CD4+ T-Cell Responses Following Repeated Annual Influenza Vaccination. J Infect Dis. 2017 Mar 1;215(5):740-749. doi: 10.1093/infdis/jiw619.
• Trieu MC, Jul-Larsen Å, Sævik M, Madsen A, Nøstbakken JK, Zhou F, Skrede S, Cox RJ. Antibody Responses to Influenza A/H1N1pdm09 Virus After Pandemic and Seasonal Influenza Vaccination in Healthcare Workers: A 5-Year Follow-up Study. Clin Infect Dis. 2019 Jan 18;68(3):382-392. doi: 10.1093/cid/ciy487.
• Manenti A, Tete SM, Mohn KG, Jul-Larsen Å, Gianchecchi E, Montomoli E, Brokstad KA, Cox RJ. Comparative analysis of influenza A(H3N2) virus hemagglutinin specific IgG subclass and IgA responses in children and adults after influenza vaccination. Vaccine. 2017 Jan 3;35(1):191-198. doi: 10.1016/j.vaccine.2016.10.024. Epub 2016 Oct 24.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 19, 2016): 255
• Original Estimated Enrollment (submitted: October 27, 2009): 8000
• Actual Study Completion Date: December 2014
• Actual Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

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 for the kinetic study

Exclusion Criteria:

• Persons with a history of anaphylaxis or serious reactions to any vaccine
• Person 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
• Suspected non-compliance

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 19 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Norway

Administrative Information

• NCT Number: NCT01003288
• Other Study ID Numbers: H1N1VAC-2009, Version 1; 2009-016456-43 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Rebecca Cox, University of Bergen
• Study Sponsor: University of Bergen
• Collaborators: Haukeland University Hospital

Investigators

• Study Chair: Per Espen Akselsen, MD; Haukeland University Hospital
• Study Chair: Haakon Sjursen, MD PhD; Haukeland University Hospital

• PRS Account: University of Bergen
• Verification Date: November 2019