Safety and Immunogenicity of Two Doses of aH5N1 Vaccine in Adult and Elderly Subjects With and Without Underlying Medical Conditions

Phase III, Stratified, Randomized, Controlled, Observer-Blind, Multicenter Study to Evaluate the Safety, Tolerability, and Immunogenicity of Two Doses of aH5N1 When Administered to Adult and Elderly Subjects With and Without Underlying Medical Conditions.

Evaluate the safety, immune response and reactogenicity of aH5N1 vaccination in adult (18 through 60 years of age) and elderly (≥61 years of age) subjects with and without underlying medical conditions.

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Biological: Novartis Investigational H5N1 vaccine; Biological: Novartis Seasonal Influenza Vaccine

• Study Type: Interventional
• Enrollment (Actual): 540
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • 001, Novartis Investigational Site
  • Dresden, Germany, 01307
    • 003, Novartis Investigational Site
  • Hamburg, Germany, 20359
    • 005, Novartis Investigational Site
  • Magdeburg, Germany, 39120
    • 006, Novartis Investigational Site
  • Rostock, Germany, 18055
    • 004, Novartis Investigational Site
  • Wuerzburg, Germany, 97070
    • 002, Novartis Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• - Male and female individuals 18 years of age and older at the time of enrollment who are mentally competent, willing and able to understand the nature and risks of the proposed study, and able to sign the consent form prior to study entry;
• Individuals who are able to comply with all study procedures and requirements;
• Healthy volunteers and volunteers specifically with underlying COPD, cardiovascular disease, diabetes mellitus, peripheral vascular disease, or renal impairment may be eligible;
• Please contact the site for additional eligibility criteria.

Exclusion Criteria:

• Individuals who are not able to follow all the required study procedures for the whole period of the study;
• Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the Investigator, may interfere with the subject's ability to participate in the study;
• Please contact the site for additional eligibility criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: aH5N1 adult; aH5N1 healthy and non-healthy adults	Biological: Novartis Investigational H5N1 vaccine; 2 doses of 0.5 ml, 3 weeks apart
Experimental: Arm 2: aH5N1 elderly; aH5N1 healthy and non-healthy elderly	Biological: Novartis Investigational H5N1 vaccine; 2 doses of 0.5 ml, 3 weeks apart
Active Comparator: Arm 3: aTIV adult; aTIV healthy and non-healthy adults	Biological: Novartis Seasonal Influenza Vaccine; 2 doses of 0.5 ml, 3 weeks apart
Active Comparator: Arm 4: aTIV elderly; aTIV healthy and non-healthy elderly	Biological: Novartis Seasonal Influenza Vaccine; 2 doses of 0.5 ml, 3 weeks apart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects achieving seroconversion	Seroconversion is defined as hemagglutination inhibition (HI) ≥1:40 for subjects who were seronegative at baseline [day 1 HI titer <1:10] or a minimum 4-fold increase in HI titer for subjects who were seropositive at baseline [day 1 HI titer ≥1:10])	day 43
Geometric mean ratios (GMRs) as determined by HI assay		day 43
Percentage of subjects with an HI titer ≥1:40		day 43
Solicited and unsolicited adverse events	In pooled age groups 18 years of age and older subjects who are healthy or with underlying medical condition who have received aTIV or aH5N1 vaccine.	day 202

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean titers (GMTs) as determined by HI	HI assay: homologous antibody responses to aH5N1 vaccine 3 weeks after first vaccination (day 22) according to CHMP immunogenicity criteria in adult and elderly subjects who are healthy or with underlying medical condition	day 1
Geometric mean ratios (GMRs) as determined by SRH		day 22
Percentage of subjects with an HI titer ≥1:40		day 22
Percentage of subjects achieving seroconversion	Seroconversion is defined as SRH area ≥25 mm2 for subjects who were seronegative at baseline [day 1 SRH area ≤3.997 mm2] or a significant increase [at least 50% increase] in SRH area for subjects who were seropositive at baseline [SRH area >3.997 mm2])	day 22
Percentage of subjects with geometric mean area ≥25 mm2		day 43
Percentage of subjects achieving seroconversion	Seroconversion is defined as HI ≥1:40 for subjects who were seronegative at baseline [day 1 HI titer <1:10] or a minimum 4-fold increase in HI titer for subjects who were seropositive at baseline [day 1 HI titer ≥1:10])	day 22
GMTs as determined by SRH	Serial radial haemolysis (SRH) assay: homologous antibody responses to aH5N1 vaccine 3 weeks after first and second vaccinations (day 22 and day 43) according to CHMP immunogenicity criteria in adult and elderly subjects who are healthy or with underlying medical condition	day 43 (3 weeks after the second vaccination)
GMRs as determined by HI		day 22
Geometric mean titers (GMTs) as determined by HI	HI assay: homologous antibody responses to aH5N1 vaccine 3 weeks after first vaccination (day 22) according to CHMP immunogenicity criteria in adult and elderly subjects who are healthy or with underlying medical condition	day 43 (3 weeks after the second vaccination)
Geometric mean titers (GMTs) as determined by HI	HI assay: homologous antibody responses to aH5N1 vaccine 3 weeks after first vaccination (day 22) according to CHMP immunogenicity criteria in adult and elderly subjects who are healthy or with underlying medical condition	day 22 (3 weeks after the first vaccination)
GMRs as determined by SRH		day 43
Percentage of subjects with an HI titer ≥1:40		day 1
Percentage of subjects with geometric mean area ≥25 mm2		day 1
Percentage of subjects with geometric mean area ≥25 mm2		day 22
Percentage of subjects achieving seroconversion	Seroconversion is defined as SRH area ≥25 mm2 for subjects who were seronegative at baseline [day 1 SRH area ≤3.997 mm2] or a significant increase [at least 50% increase] in SRH area for subjects who were seropositive at baseline [SRH area >3.997 mm2])	day 43
GMTs as determined by SRH	Serial radial haemolysis (SRH) assay: homologous antibody responses to aH5N1 vaccine 3 weeks after first and second vaccinations (day 22 and day 43) according to CHMP immunogenicity criteria in adult and elderly subjects who are healthy or with underlying medical condition	day 1
Geometric mean ratios (GMRs) as determined by SRH		day 43 (3 weeks after the second vaccination)

Collaborators and Investigators

• Sponsor: Seqirus
• Collaborators: Novartis Vaccines

Publications and helpful links

General Publications

• Atmar RL, Keitel WA, Patel SM, Katz JM, She D, El Sahly H, Pompey J, Cate TR, Couch RB. Safety and immunogenicity of nonadjuvanted and MF59-adjuvanted influenza A/H9N2 vaccine preparations. Clin Infect Dis. 2006 Nov 1;43(9):1135-42. doi: 10.1086/508174. Epub 2006 Sep 25.
• Banzhoff A, Gasparini R, Laghi-Pasini F, Staniscia T, Durando P, Montomoli E, Capecchi PL, di Giovanni P, Sticchi L, Gentile C, Hilbert A, Brauer V, Tilman S, Podda A. MF59-adjuvanted H5N1 vaccine induces immunologic memory and heterotypic antibody responses in non-elderly and elderly adults. PLoS One. 2009;4(2):e4384. doi: 10.1371/journal.pone.0004384. Epub 2009 Feb 6. Erratum In: PLoS ONE. 2009;4(3). doi: 10.1371/annotation/5f2ae0fb-53f1-48c2-aa19-9114765ba029. Capecchi, Pamela [corrected to Capecchi, Pier Leopoldo].
• Podda A. The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine. Vaccine. 2001 Mar 21;19(17-19):2673-80. doi: 10.1016/s0264-410x(00)00499-0.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: March 7, 2014
• First Submitted That Met QC Criteria: March 17, 2014
• First Posted (Estimate): March 19, 2014

Study Record Updates

• Last Update Posted (Estimate): November 4, 2016
• Last Update Submitted That Met QC Criteria: November 3, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Influenza; H5N1; Adjuvanted vaccine; aH5N1; H5N1 vaccine; Pandemic Influenza vaccine; MF59, Adjuvant, Avian flu; Underlying medical conditions; Underlying cardiovascular medical condition; Pandemic vaccine; Charlson Comorbidity Index (CCI)
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Disease; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Gastrointestinal Agents; Cathartics; Vaccines; Lactitol
• Other Study ID Numbers: V87_25