Safety and Immunogenicity of Two Doses of H5N1 Influenza Vaccine in Healthy Adults

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Adjuvanted H5N1 pandemic influenza vaccine

About this trial

This is an interventional prevention trial for Pandemic H5N1 Influenza focused on measuring Influenza, Pandemic, H5N1, Adults

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy adult subjects 18 to 64 years of age,
Individuals willing to provide written informed consent,
Individuals in good health,
Individuals willing to allow for their serum samples to be stored beyond the study period.

Exclusion Criteria:

Individuals not able to understand and follow study procedures,
History of any significant illness,
History of any chronic medical condition or progressive disease,
Presence of medically significant cancer,
Known or suspected impairment/alteration of immune function,
Presence of any progressive or severe neurologic disorder,
Presence of any bleeding disorders or conditions that prolongs bleeding time,
History of allergy to vaccine components,
Receipt of any other investigational product within 30 days prior to entry into the study,
History of previous H5N1 vaccination,
Receipt of any other type of seasonal vaccination within 2 months prior to entry into the study,
Receipt of any other vaccine within 2 weeks prior to entry into the study
Body temperature ≥38°C.0 (≥100.4° F) and/or acute illness within 3 days of intended study vaccination,
Pregnant or breast feeding,
Females of childbearing potential refusing to use acceptable method of birth control,
Body mass index (BMI) ≥ 35 kg/m2,
History of drug or alcohol abuse,
Any planned surgery during study period,
Individuals conducting the study and their immediate family members,
Individuals with behavioral or cognitive impairment or psychiatric diseases.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

aH5N1c-High Dose

aH5N1c-Low dose

Arm Description

Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.

Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.

Outcomes

Primary Outcome Measures

Percentages Of Subjects Achieving Hemagglutinin Inhibition (HI) Titers ≥40 Against A/H5N1 Strain.

The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion. CBER criterion for the adult population is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.

Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain.

Immunogenicity was measured in terms of the percentages of subjects achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criterion. Seroconversion is defined as either a) in subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or b) in subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion for the adult population is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.

Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination.

Safety was assessed using the number of subjects who reported solicited local and systemic AEs following vaccination with either low or high dose of aH5N1c vaccine.

Number of Subjects Reporting Unsolicited AEs After Any Vaccination.

Safety was assessed using the number of subjects who reported any unsolicited adverse events, adverse events possibly or probably related to study vaccine, serious adverse events (SAEs), new onset of chronic diseases (NOCDs), medically attended AEs, AEs of special interest (AESIs), AEs leading to withdrawal from study following vaccination with either low or high dose of aH5N1c vaccine.

Secondary Outcome Measures

Geometric Mean Ratios Against A/H5N1 Strain Following 2-dose Vaccination Schedule of Either Low Dose or High Dose aH5N1c Vaccine.

Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c is reported. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criterion if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5 for subjects 18-60 years of age.

Percentages Of Subjects With HI Titers ≥40 Against A/H5N1 Strain.

Immunogenicity was assessed in terms of percentage of subjects achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%.

Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain.

Immunogenicity was assessed in terms of percentages of subjects achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as: a) for subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or b) for subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is >40%.

Full Information

NCT ID

NCT01776541

First Posted

January 20, 2013

Last Updated

January 20, 2015

Sponsor

Novartis Vaccines

Collaborators

Department of Health and Human Services

1. Study Identification

Unique Protocol Identification Number

NCT01776541

Brief Title

Safety and Immunogenicity of Two Doses of H5N1 Influenza Vaccine in Healthy Adults

Official Title

A Phase II, Randomized, Observer-Blind,Multi-Center, Study to Evaluate Safety, Tolerability and Immunogenicity of an Adjuvanted Cell Culture-Derived H5N1 Subunit Influenza Virus Vaccine at Two Different Formulations in Healthy Adult Subjects.

Study Type

Interventional

2. Study Status

Record Verification Date

January 2015

Overall Recruitment Status

Completed

Study Start Date

January 2013 (undefined)

Primary Completion Date

June 2013 (Actual)

Study Completion Date

May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Vaccines

Collaborators

Department of Health and Human Services

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

Evaluate Safety, Tolerability and Immune Response of Adjuvanted H5N1 Cell Culture Derived Influenza Vaccine in Adult Subjects.

6. Conditions and Keywords

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

Pandemic H5N1 Influenza

Keywords

Influenza, Pandemic, H5N1, Adults

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

979 (Actual)

8. Arms, Groups, and Interventions

Arm Title

aH5N1c-High Dose

Arm Type

Experimental

Arm Description

Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.

Arm Title

aH5N1c-Low dose

Arm Type

Experimental

Arm Description

Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.

Intervention Type

Biological

Intervention Name(s)

Adjuvanted H5N1 pandemic influenza vaccine

Intervention Description

Comparison of two doses of aH5N1c vaccine

Primary Outcome Measure Information:

Title

Percentages Of Subjects Achieving Hemagglutinin Inhibition (HI) Titers ≥40 Against A/H5N1 Strain.

Description

The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion. CBER criterion for the adult population is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.

Time Frame

Three weeks after 2nd vaccination (day 43)

Title

Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain.

Description

Immunogenicity was measured in terms of the percentages of subjects achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criterion. Seroconversion is defined as either a) in subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or b) in subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion for the adult population is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.

Time Frame

Three weeks after 2nd vaccination (day 43)

Title

Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination.

Description

Safety was assessed using the number of subjects who reported solicited local and systemic AEs following vaccination with either low or high dose of aH5N1c vaccine.

Time Frame

From day 1 through day 7 after any vaccination.

Title

Number of Subjects Reporting Unsolicited AEs After Any Vaccination.

Description

Safety was assessed using the number of subjects who reported any unsolicited adverse events, adverse events possibly or probably related to study vaccine, serious adverse events (SAEs), new onset of chronic diseases (NOCDs), medically attended AEs, AEs of special interest (AESIs), AEs leading to withdrawal from study following vaccination with either low or high dose of aH5N1c vaccine.

Time Frame

Any unsolicited AEs - day 1 through day 22 after any vaccination. SAEs, NOCDs. medically attended AEs, AESIs, AEs leading to study withdrawal- day 1 to day 387

Secondary Outcome Measure Information:

Title

Geometric Mean Ratios Against A/H5N1 Strain Following 2-dose Vaccination Schedule of Either Low Dose or High Dose aH5N1c Vaccine.

Description

Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c is reported. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criterion if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5 for subjects 18-60 years of age.

Time Frame

Day 1; day 22; day 43 and day 387

Title

Percentages Of Subjects With HI Titers ≥40 Against A/H5N1 Strain.

Description

Immunogenicity was assessed in terms of percentage of subjects achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%.

Time Frame

Day 1, day 22, day 43 and day 387

Title

Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain.

Description

Immunogenicity was assessed in terms of percentages of subjects achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as: a) for subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or b) for subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is >40%.

Time Frame

Day 22, day 43 and day 387

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy adult subjects 18 to 64 years of age, Individuals willing to provide written informed consent, Individuals in good health, Individuals willing to allow for their serum samples to be stored beyond the study period. Exclusion Criteria: Individuals not able to understand and follow study procedures, History of any significant illness, History of any chronic medical condition or progressive disease, Presence of medically significant cancer, Known or suspected impairment/alteration of immune function, Presence of any progressive or severe neurologic disorder, Presence of any bleeding disorders or conditions that prolongs bleeding time, History of allergy to vaccine components, Receipt of any other investigational product within 30 days prior to entry into the study, History of previous H5N1 vaccination, Receipt of any other type of seasonal vaccination within 2 months prior to entry into the study, Receipt of any other vaccine within 2 weeks prior to entry into the study Body temperature ≥38°C.0 (≥100.4° F) and/or acute illness within 3 days of intended study vaccination, Pregnant or breast feeding, Females of childbearing potential refusing to use acceptable method of birth control, Body mass index (BMI) ≥ 35 kg/m2, History of drug or alcohol abuse, Any planned surgery during study period, Individuals conducting the study and their immediate family members, Individuals with behavioral or cognitive impairment or psychiatric diseases.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Vaccines and Diagnostics

Organizational Affiliation

Novartis Vaccines

Official's Role

Study Chair

Facility Information:

Facility Name

1 Miami Research Associates

City

Miami

State/Province

Florida

ZIP/Postal Code

33143

Country

United States

Facility Name

2 Mercy Health Research

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63141

Country

United States

Facility Name

3 Saint Louis University

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63141

Country

United States

Facility Name

4 Benchmark Medical Research

City

Austin

State/Province

Texas

ZIP/Postal Code

78705

Country

United States

Facility Name

48 Hunter Clinical Research

City

Newcastle

State/Province

New South Wales

ZIP/Postal Code

2292

Country

Australia

Facility Name

46 CMAX

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

5000

Country

Australia

Facility Name

47 Linear Clinical Research

City

Nedlands

State/Province

Western Australia

ZIP/Postal Code

6009

Country

Australia

Facility Name

80 Faculty of Tropical Medicine

City

Bangkok

ZIP/Postal Code

1040

Country

Thailand

12. IPD Sharing Statement

Citations:

PubMed Identifier

30968056

Citation

Frey SE, Shakib S, Chanthavanich P, Richmond P, Smith T, Tantawichien T, Kittel C, Jaehnig P, Mojares Z, Verma B, Kanesa-Thasan N, Hohenboken M. Safety and Immunogenicity of MF59-Adjuvanted Cell Culture-Derived A/H5N1 Subunit Influenza Virus Vaccine: Dose-Finding Clinical Trials in Adults and the Elderly. Open Forum Infect Dis. 2019 Mar 1;6(4):ofz107. doi: 10.1093/ofid/ofz107. eCollection 2019 Apr.

Results Reference

derived

Pandemic H5N1 Influenza

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

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