Safety and Immunogenicity of Two Doses of a Tetravalent Influenza Vaccine in Adults Aged 18 Years and Above

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

MF59-eTIV-H5N1+ placebo /pandemic influenza vaccine

Pandemic influenza vaccine + placebo /MF59-eTIV-H5N1

Pandemic influenza vaccine + seasonal influenza vaccine /pandemic influenza vaccine

Pandemic influenza vaccine + placebo / MF59-eTIV-H5N1

Pandemic influenza vaccine + seasonal influenza vaccine / pandemic influenza vaccine

MF59-eTIV-H5N1 + Placebo/pandemic influenza vaccine

About this trial

This is an interventional prevention trial for Influenza focused on measuring avian flu, seasonal influenza vaccine, influenza vaccine, prepandemic vaccine, virus strain with the potential to cause pandemic, tetravalent vaccine, Prophylaxis of influenza

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy subjects (aged 18 years and above) who have signed an informed consent form

Exclusion Criteria:

Any acute or chronic illness
Receipt of seasonal influenza vaccine for the current season 2007/2008
Known or suspected impairment/alteration of immune function
Receipt of another vaccine within 3 weeks prior to Visit 1 or planned vaccination within 3 weeks following the last study vaccination
Any serious disease
Hypersensitivity to eggs, chicken protein, chicken feathers, influenza viral protein,neomycin or kanamycin or any other component of the study vaccine
Receipt of blood, blood products or immunoglobulins 3 months prior to vaccination

Sites / Locations

ATRIUM Gesundheitszentrum;
International Medicine & Public Health Dept. of Infect. Diseases

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

T/P-A

A/P-T

A/S-A

T/P-A (V2 blood draw)

A/P-T (V2 blood draw)

A/S-A (V2 blood draw)

Arm Description

One dose of the tetravalent influenza vaccine (T) and concomitantly, but in a different arm, one dose of placebo (P) on day 1, followed by Aflunov (A) on day 22

One dose of the Aflunov (A) and concomitantly, but in a different arm, one dose of placebo (P) on day 1, followed by Tetravalent influenza vaccine (T) on day 22.

One dose of Aflunov (A) and concomitantly, but in a different arm, one dose of licensed seasonal vaccine (S) on day 1, followed Aflunov (A) on day 22.

One dose of the tetravalent influenza vaccine (T) and concomitantly, but in a different arm, one dose of placebo (P) on day 1, followed by a blood draw at visit 2 (V2) prior to Aflunov (A) vaccination on day 22.

One dose of the Aflunov(A) and concomitantly, but in a different arm, one dose of placebo (P) on day 1, followed by additional blood draw at visit 2 (V2) prior to the Tetravalent influenza vaccination (T) on day 22.

One dose of Aflunov (A)and concomitantly, but in a different arm, one dose of licensed seasonal vaccine (S) on day 1, followed by an additional blood draw at visit 2 (V2) prior to Aflunov (A) vaccination on day 22.

Outcomes

Primary Outcome Measures

To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43.

The antibody response was determined by SRH assay. Geometric mean areas (GMAs) and geometric mean ratios (GMRs) in the SRH assay were used to demonstrate the equivalence. The statistical analysis was done based on the GMRs.

Secondary Outcome Measures

Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination

Local reactions were collected up to 7 days after 1st vaccinations. All subjects were instructed to complete a diary card to record local reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization. The table represents local reactions after first vaccination in each arm differently.

Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination

Local reactions were collected up to 7 days after 1st vaccinations. All subjects were instructed to complete a diary card to record local reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization.

Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations.

Systemic reactions were collected upto 7 days after 1st and 2nd vaccinations. All subjects were instructed to complete a diary card to record systemic reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization.

Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain

Measurement of immunogenicity in terms of significant increase in antibody titer and Seroconversion. Significant increase in antibody titer is defined as at least a four-fold increase from non-negative pre-vaccination serum (≥ 10) for HI or a 50% increase in area for SRH. Seroconversion is defined as negative pre-vaccination serum / post-vaccination titer ≥40 for HI (area ≥25 mm2 for SRH)

Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2

Measurement of immunogenicity in terms of percentage of subjects achieving a titre ≥ 40/area ≥ 25mm^2 after immunization as determined by HI (Haemagglutination Inhibition), MN(Microneutralization) and SRH assay.

Antibody Response Determined by HI and MN Assay.

Measurement of immunogenicity in terms of Geometric mean titers (GMTs) as determined by HI and MN assay.

Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination.

The Cell Mediated Immunity (CMI) response was evaluated in a randomly selected subgroup of approximately 92 subjects from all the vaccine groups out of a total of 601 enrolled subjects. Frequency of circulating memory B cells (MBC), capable of differentiating in vitro into cell secreting IgG (Immunoglobulin G) antibodies specific for H5N1 (the subunit from A/Vietnam/1194/2004) or for H1N1 (the subunit from A/Solomon Island/3/2006) were determined by an ELISA-coupled limiting dilution assay.The frequency of H5N1-IgG MBC and H1N1-IgG MBC was expressed as percentages (%) of total IgG producing MBC.

Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit

Frequency and functionality of vaccine antigen-specific CD4+ (cluster of differentiation 4) T cells was assessed in peripheral blood (PBMC) taken at days 1, 22 and 43 after in vitro stimulation with: Library of 70 peptides spanning the whole H5 A/Vietnam/1194/2004 protein (H5 pool of 70 Vietnam) H5N1 subunit from A/Vietnam/1194/2004 (H5N1 Vietnam) H3N2 subunit from A/ Wisconsin/67/2005 (H3N2 Wisconsin) H1N1 subunit from A/Solomon Islands/3/2006 (H1N1 Solomon Islands) Polyclonal stimulus agonistic aCD3 mAb [monoclonal antibody (aCD3)]. The change in frequency of T-cells was measured.

Full Information

NCT ID

NCT00620815

First Posted

February 12, 2008

Last Updated

March 3, 2016

Sponsor

Novartis Vaccines

1. Study Identification

Unique Protocol Identification Number

NCT00620815

Brief Title

Safety and Immunogenicity of Two Doses of a Tetravalent Influenza Vaccine in Adults Aged 18 Years and Above

Official Title

A Phase II, Randomized, Placebo-controlled, Observer-blind, Multi Center Study on the Safety and Immunogenicity of Novartis Tetravalent Influenza Vaccine (Containing Both Interpandemic Strains and H5N1) in Adults Aged 18 Years and Above

Study Type

Interventional

2. Study Status

Record Verification Date

March 2016

Overall Recruitment Status

Completed

Study Start Date

November 2007 (undefined)

Primary Completion Date

January 2008 (Actual)

Study Completion Date

December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Vaccines

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

Evaluate the immune response and reactogenicity of H5N1 vaccination in adults aged 18 years and above (as part of a tetravalent vaccine)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Influenza

Keywords

avian flu, seasonal influenza vaccine, influenza vaccine, prepandemic vaccine, virus strain with the potential to cause pandemic, tetravalent vaccine, Prophylaxis of influenza

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Investigator

Allocation

Randomized

Enrollment

601 (Actual)

8. Arms, Groups, and Interventions

Arm Title

T/P-A

Arm Type

Experimental

Arm Description

One dose of the tetravalent influenza vaccine (T) and concomitantly, but in a different arm, one dose of placebo (P) on day 1, followed by Aflunov (A) on day 22

Arm Title

A/P-T

Arm Type

Experimental

Arm Description

One dose of the Aflunov (A) and concomitantly, but in a different arm, one dose of placebo (P) on day 1, followed by Tetravalent influenza vaccine (T) on day 22.

Arm Title

A/S-A

Arm Type

Active Comparator

Arm Description

One dose of Aflunov (A) and concomitantly, but in a different arm, one dose of licensed seasonal vaccine (S) on day 1, followed Aflunov (A) on day 22.

Arm Title

T/P-A (V2 blood draw)

Arm Type

Experimental

Arm Description

One dose of the tetravalent influenza vaccine (T) and concomitantly, but in a different arm, one dose of placebo (P) on day 1, followed by a blood draw at visit 2 (V2) prior to Aflunov (A) vaccination on day 22.

Arm Title

A/P-T (V2 blood draw)

Arm Type

Experimental

Arm Description

One dose of the Aflunov(A) and concomitantly, but in a different arm, one dose of placebo (P) on day 1, followed by additional blood draw at visit 2 (V2) prior to the Tetravalent influenza vaccination (T) on day 22.

Arm Title

A/S-A (V2 blood draw)

Arm Type

Active Comparator

Arm Description

One dose of Aflunov (A)and concomitantly, but in a different arm, one dose of licensed seasonal vaccine (S) on day 1, followed by an additional blood draw at visit 2 (V2) prior to Aflunov (A) vaccination on day 22.

Intervention Type

Biological

Intervention Name(s)

MF59-eTIV-H5N1+ placebo /pandemic influenza vaccine

Intervention Description

Tetravalent influenza vaccine (MF59-eTIV-H5N1)and placebo on day 1 followed 3-5 weeks later by pandemic influenza vaccine, including serology blood draw at V1+V3.

Intervention Type

Biological

Intervention Name(s)

Pandemic influenza vaccine + placebo /MF59-eTIV-H5N1

Intervention Description

Pandemic influenza vaccine plus placebo on day 1 followed 3-5 weeks later by tetravalent influenza vaccine (MF59-eTIV-H5N1), including serology blood draw at V1+V3.

Intervention Type

Biological

Intervention Name(s)

Pandemic influenza vaccine + seasonal influenza vaccine /pandemic influenza vaccine

Intervention Description

Pandemic influenza vaccine plus seasonal influenza vaccine, 3-5 weeks later pandemic influenza vaccine , including serology blood draw at V1+V3.

Intervention Type

Biological

Intervention Name(s)

Pandemic influenza vaccine + placebo / MF59-eTIV-H5N1

Intervention Description

Pandemic influenza vaccine plus placebo followed 3-5 weeks later by tetravalent influenza vaccine (MF59-eTIV-H5N1), including serology blood draw at V1, V2 and V3.

Intervention Type

Biological

Intervention Name(s)

Pandemic influenza vaccine + seasonal influenza vaccine / pandemic influenza vaccine

Intervention Description

Pandemic influenza vaccine plus seasonal influenza vaccine followed 3-5 weeks later by pandemic influenza vaccine, including serology blood draw at V1, V2 and V3.

Intervention Type

Biological

Intervention Name(s)

MF59-eTIV-H5N1 + Placebo/pandemic influenza vaccine

Intervention Description

Tetravalent influenza vaccine (MF59-eTIV-H5N1)plus placebo followed 3-5 weeks later by pandemic influenza vaccine, including serology blood draw at V1, V2 and V3.

Primary Outcome Measure Information:

Title

To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43.

Description

The antibody response was determined by SRH assay. Geometric mean areas (GMAs) and geometric mean ratios (GMRs) in the SRH assay were used to demonstrate the equivalence. The statistical analysis was done based on the GMRs.

Time Frame

up to day 43

Secondary Outcome Measure Information:

Title

Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination

Description

Local reactions were collected up to 7 days after 1st vaccinations. All subjects were instructed to complete a diary card to record local reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization. The table represents local reactions after first vaccination in each arm differently.

Time Frame

Up to 7 days after 1st vaccination

Title

Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination

Description

Local reactions were collected up to 7 days after 1st vaccinations. All subjects were instructed to complete a diary card to record local reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization.

Time Frame

Up to 7 days after 2nd vaccination

Title

Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations.

Description

Systemic reactions were collected upto 7 days after 1st and 2nd vaccinations. All subjects were instructed to complete a diary card to record systemic reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization.

Time Frame

7 days after 1st and 2nd vaccinations each

Title

Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain

Description

Measurement of immunogenicity in terms of significant increase in antibody titer and Seroconversion. Significant increase in antibody titer is defined as at least a four-fold increase from non-negative pre-vaccination serum (≥ 10) for HI or a 50% increase in area for SRH. Seroconversion is defined as negative pre-vaccination serum / post-vaccination titer ≥40 for HI (area ≥25 mm2 for SRH)

Time Frame

up to day 43

Title

Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2

Description

Measurement of immunogenicity in terms of percentage of subjects achieving a titre ≥ 40/area ≥ 25mm^2 after immunization as determined by HI (Haemagglutination Inhibition), MN(Microneutralization) and SRH assay.

Time Frame

Up to 43 days

Title

Antibody Response Determined by HI and MN Assay.

Description

Measurement of immunogenicity in terms of Geometric mean titers (GMTs) as determined by HI and MN assay.

Time Frame

Up to 43 days

Title

Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination.

Description

The Cell Mediated Immunity (CMI) response was evaluated in a randomly selected subgroup of approximately 92 subjects from all the vaccine groups out of a total of 601 enrolled subjects. Frequency of circulating memory B cells (MBC), capable of differentiating in vitro into cell secreting IgG (Immunoglobulin G) antibodies specific for H5N1 (the subunit from A/Vietnam/1194/2004) or for H1N1 (the subunit from A/Solomon Island/3/2006) were determined by an ELISA-coupled limiting dilution assay.The frequency of H5N1-IgG MBC and H1N1-IgG MBC was expressed as percentages (%) of total IgG producing MBC.

Time Frame

Three weeks after first vaccination (day 22) and three weeks after second vaccination (day 43)

Title

Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit

Description

Frequency and functionality of vaccine antigen-specific CD4+ (cluster of differentiation 4) T cells was assessed in peripheral blood (PBMC) taken at days 1, 22 and 43 after in vitro stimulation with: Library of 70 peptides spanning the whole H5 A/Vietnam/1194/2004 protein (H5 pool of 70 Vietnam) H5N1 subunit from A/Vietnam/1194/2004 (H5N1 Vietnam) H3N2 subunit from A/ Wisconsin/67/2005 (H3N2 Wisconsin) H1N1 subunit from A/Solomon Islands/3/2006 (H1N1 Solomon Islands) Polyclonal stimulus agonistic aCD3 mAb [monoclonal antibody (aCD3)]. The change in frequency of T-cells was measured.

Time Frame

Three weeks after 1st vaccination (day 22) and three weeks after 2nd vaccination (day 43)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy subjects (aged 18 years and above) who have signed an informed consent form Exclusion Criteria: Any acute or chronic illness Receipt of seasonal influenza vaccine for the current season 2007/2008 Known or suspected impairment/alteration of immune function Receipt of another vaccine within 3 weeks prior to Visit 1 or planned vaccination within 3 weeks following the last study vaccination Any serious disease Hypersensitivity to eggs, chicken protein, chicken feathers, influenza viral protein,neomycin or kanamycin or any other component of the study vaccine Receipt of blood, blood products or immunoglobulins 3 months prior to vaccination

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Vaccines and Diagnostics

Organizational Affiliation

Novartis

Official's Role

Study Chair

Facility Information:

Facility Name

ATRIUM Gesundheitszentrum;

City

Holzkirchen

ZIP/Postal Code

83607

Country

Germany

Facility Name

International Medicine & Public Health Dept. of Infect. Diseases

City

Munich

ZIP/Postal Code

80799

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

24047817

Citation

Herbinger KH, von Sonnenburg F, Nothdurft HD, Perona P, Borkowski A, Fragapane E, Nicolay U, Clemens R. A phase II study of an investigational tetravalent influenza vaccine formulation combining MF59(R): adjuvanted, pre-pandemic, A/H5N1 vaccine and trivalent seasonal influenza vaccine in healthy adults. Hum Vaccin Immunother. 2014;10(1):92-9. doi: 10.4161/hv.26495. Epub 2013 Sep 20.

Results Reference

derived

Influenza

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial