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

Influenza, Human Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02091908
• Other study ID #: V87_25
• Status: Completed
• Phase: Phase 3
• First received: March 7, 2014
• Last updated: November 3, 2016
• Start date: April 2014
• Est. completion date: April 2015

Study information

• Verified date: November 2016
• Source: Seqirus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 540
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Disease
• Influenza, Human

Intervention

Biological:
• Novartis Investigational H5N1 vaccine
2 doses of 0.5 ml, 3 weeks apart
• Novartis Investigational H5N1 vaccine
2 doses of 0.5 ml, 3 weeks apart
• Novartis Seasonal Influenza Vaccine
2 doses of 0.5 ml, 3 weeks apart
• Novartis Seasonal Influenza Vaccine
2 doses of 0.5 ml, 3 weeks apart

Locations

Country	Name	City	State
Germany	001, Novartis Investigational Site	Berlin
Germany	003, Novartis Investigational Site	Dresden
Germany	005, Novartis Investigational Site	Hamburg
Germany	006, Novartis Investigational Site	Magdeburg
Germany	004, Novartis Investigational Site	Rostock
Germany	002, Novartis Investigational Site	Wuerzburg

Sponsors (2)

Lead Sponsor	Collaborator
Seqirus	Novartis Vaccines

Country where clinical trial is conducted

Germany, 

References & Publications (3)

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. — View Citation

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. Erratum in: PLoS ONE. 2009;4(3). doi: 10.1371/annotation/5f2ae0fb-53f1-48c2-aa19-9114765ba029. Capecchi, Pamela [corrected to Capecchi, Pier Leopoldo]. — View Citation

Podda A. The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine. Vaccine. 2001 Mar 21;19(17-19):2673-80. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Geometric mean ratios (GMRs) as determined by HI assay		day 43	No
Primary	Percentage of subjects with an HI titer =1:40		day 43	No
Primary	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	Yes
Secondary	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	No
Secondary	Geometric mean ratios (GMRs) as determined by SRH		day 22	No
Secondary	Percentage of subjects with an HI titer =1:40		day 22	No
Secondary	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	No
Secondary	Percentage of subjects with geometric mean area =25 mm2		day 43	No
Secondary	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	No
Secondary	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)	No
Secondary	GMRs as determined by HI		day 22	No
Secondary	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)	No
Secondary	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)	No
Secondary	GMRs as determined by SRH		day 43	No
Secondary	Percentage of subjects with an HI titer =1:40		day 1	No
Secondary	Percentage of subjects with geometric mean area =25 mm2		day 1	No
Secondary	Percentage of subjects with geometric mean area =25 mm2		day 22	No
Secondary	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	No
Secondary	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	No
Secondary	Geometric mean ratios (GMRs) as determined by SRH		day 43 (3 weeks after the second vaccination)	No