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Evaluating the Safety and Immune Response to an H5N1 Influenza Vaccine in People Who Have Previously Received an H5N1 or H7N3 Influenza Vaccine and in People Who Have Never Received a Live Attenuated Influenza Vaccine

Primary Purpose

H5N1 Influenza

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

H5N1 Vaccine

About this trial

This is an interventional prevention trial for H5N1 Influenza

Eligibility Criteria

22 Years - 54 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

In general good health, without significant medical illness, physical examination findings, or significant laboratory abnormalities as determined by the investigator
Available for the duration of the trial
Willing to participate in the study as evidenced by signing the informed consent document
Willing to allow storage and testing of laboratory samples for future research
Received two doses of live attenuated H5N1 or H7N3 vaccine in a prior trial (Study Groups 1, 2, and 3) or LAIV and H5 naïve (Study Groups 4 and 5)
Willing to forego seasonal LAIV for the duration of the trial (until 6 months after the last vaccination)
Female participants must agree to use effective birth control methods for the duration of the study. More information on this criterion can be found in the protocol.

Exclusion Criteria:

Pregnant, as determined by a positive beta-human choriogonadotropin (HCG) test
Currently breastfeeding
Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urine testing
Behavioral or cognitive impairment or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and cooperate with the study protocol
Have medical, occupational, or family problems as a result of alcohol or illicit drug use during the 12 months prior to study entry
Other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol
History of anaphylaxis
History of life-threatening reaction to prior influenza vaccine
Current diagnosis of asthma or reactive airway disease (within the 2 years prior to study entry)
Positive enzyme-linked immunosorbent assay (ELISA) and confirmatory Western blot tests for HIV-1
Positive ELISA and confirmatory test (e.g., recombinant immunoblot assay [RIBA]) for hepatitis C virus (HCV)
Positive hepatitis B virus surface antigen (HBsAg) by ELISA
Known immunodeficiency syndrome
History of Guillain-Barré syndrome
Use of chronic oral or intravenous administration (greater than or equal to 14 days) of immunosuppressive doses of steroids, i.e., prednisone greater than 10 mg per day, immunosuppressants or other immune-modifying drugs within 30 days of starting this study
Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to study vaccination
Receipt of blood or blood-derived products (including immunoglobulin) within 6 months prior to study vaccination
Receipt of another investigational vaccine or drug within 30 days prior to study vaccination
Allergy to eggs or egg products

In addition to the above, participants in the H5 and LAIV-naïve groups must also not experience any of the following:

Previous enrollment in an H5 influenza vaccine trial or in any study of an avian influenza (AI) vaccine
Seropositive to the H5N1 influenza A virus (serum HI titer greater than 1:8)
Previous receipt of FluMist or any intranasal live attenuated influenza vaccine

Sites / Locations

Centers for Immunization Research (CIR) - John Hopkins Bloomburg School of Public Health

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Group 1 (Previously Received H5N1 VN 04 ca Vaccine)

Group 2 (Previously Received H5N1 HK 03 ca Vaccine)

Group 3 (Previously Received H7N3 ca Vaccine)

Group 4 (Have Not Previously Received LAIV)

Group 5 (Have Not Previously Received LAIV)

Arm Description

Participants will have previously received two doses of 10^7.5 tissue culture infectious dose (TCID)50 of H5N1 A/VN/1203/04 x A/AA/6/60 ca LAIV (H5N1 VN 04 ca). In this study, they will receive one dose of the H5N1 vaccine at baseline.

Participants will have previously received two doses of 10^7.5 TCID50 of H5N1 A/HK/213/03 x A/AA/6/60 ca LAIV (H5N1 HK 03 ca). In this study, they will receive one dose of the H5N1 vaccine at baseline.

Participants will have previously received two doses of 10^7.5 TCID50 of H7N3 A/ck/BC/CN-6/04 x A/AA/6/60 ca LAIV (H7N3 ca). In this study, they will receive one dose of the H5N1 vaccine at baseline.

Participants will have not previously received an LAIV of any kind. In this study, they will receive one dose of the H5N1 vaccine at baseline.

Participants will have not previously received an LAIV of any kind. In this study, they will receive two doses of the H5N1 vaccine at baseline and Day 28.

Outcomes

Primary Outcome Measures

Characterize the kinetics and magnitude of the antibody response (measured by hemagglutination inhibition assay [HI] and microneutralization assay [MN]) to a single 45 micrograms dose of H5N1 vaccine

Secondary Outcome Measures

Assess the reactogenicity of the H5N1 vaccine in previous recipients of LAIV

Reactogenicity will be followed for 7 days; serious adverse events (SAEs) will be followed for 6 months after the last immunization.

Assess the immune response to the inactivated H5N1 vaccine (A/VN/1203/04)

Immune response will be assessed via the following: Evaluation of memory B-cell responses to H5N1 by enzyme-linked immunosorbent spot (ELISPOT) Evaluation of HI antibody responses to heterologous non-Clade 1 H5N1 viruses Evaluation of T-cell mediated responses to H5N1 influenza viruses to the following: Clade 1 H5N1 viruses Heterologous cross-clade H5N1 viruses

Full Information

NCT ID

NCT01443663

First Posted

September 28, 2011

Last Updated

February 5, 2016

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT01443663

Brief Title

Evaluating the Safety and Immune Response to an H5N1 Influenza Vaccine in People Who Have Previously Received an H5N1 or H7N3 Influenza Vaccine and in People Who Have Never Received a Live Attenuated Influenza Vaccine

Official Title

Immunogenicity and Safety Study of a 45 Micrograms Dose of Inactivated, Unadjuvanted H5N1 Influenza Vaccine in Prior Recipients of Live Attenuated H5N1 and H7N3 Influenza Vaccines and in H5 and Live Attenuated Vaccine Naïve Individuals

Study Type

Interventional

2. Study Status

Record Verification Date

February 2016

Overall Recruitment Status

Completed

Study Start Date

October 2011 (undefined)

Primary Completion Date

September 2012 (Actual)

Study Completion Date

March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

H5N1 is an influenza virus that has the potential to cause an influenza pandemic. This study will evaluate the safety and immune response to an H5N1 influenza vaccine in people who have previously received one of two versions of an H5N1 vaccine or have previously received an H7N3 vaccine and in people who have not previously received any live attenuated influenza vaccine (LAIV).

Detailed Description

Avian influenza viruses, including H1N1 and H5N1, are capable of causing an influenza pandemic. The 2009 H1N1 pandemic caused approximately 10,000 deaths in the United States, and H1N1 and H5N1 influenza outbreaks have been observed in countries around the world. Previous studies have shown that people who received an H5N1 vaccine and then received another H5N1 vaccine years later had a greater antibody response than people who only received a single vaccination. This study will evaluate the safety and immune response to an inactivated H5N1 vaccine in healthy adults who have previously received two doses of the H5N1 VN 04 ca vaccine or the H5N1 HK 03 ca vaccine or who have previously received two doses of the H7N3 ca vaccine, which is another avian influenza vaccine. The study will also enroll people who have not previously received any LAIV. Participants who previously received an H5N1 or H7N3 vaccine will receive one injection of the H5N1 vaccine at baseline. Participants who have not received any previous LAIV will be randomly assigned to receive either one dose or two doses of the H5N1 vaccine. At a baseline study visit, participants will undergo a medical history review, physical examination, blood collection, vital sign measurements, and a pregnancy test for females. All participants will then receive one injection of the vaccine in the upper arm. After receiving the vaccine, participants will remain in the clinic for 30 minutes for observation and monitoring. All participants will attend additional study visits at Days 3 and 7. Participants who are assigned to receive one vaccination will also attend study visits at Days 28, 56, and 180. Participants who are assigned to receive two vaccinations will attend study visits at Days 28 (at which time they will receive the second vaccination), 35, 56, 84, and 208. Select baseline study procedures will occur at the follow-up study visits.

6. Conditions and Keywords

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

H5N1 Influenza

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

69 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1 (Previously Received H5N1 VN 04 ca Vaccine)

Arm Type

Experimental

Arm Description

Arm Title

Group 2 (Previously Received H5N1 HK 03 ca Vaccine)

Arm Type

Experimental

Arm Description

Arm Title

Group 3 (Previously Received H7N3 ca Vaccine)

Arm Type

Experimental

Arm Description

Participants will have previously received two doses of 10^7.5 TCID50 of H7N3 A/ck/BC/CN-6/04 x A/AA/6/60 ca LAIV (H7N3 ca). In this study, they will receive one dose of the H5N1 vaccine at baseline.

Arm Title

Group 4 (Have Not Previously Received LAIV)

Arm Type

Experimental

Arm Description

Participants will have not previously received an LAIV of any kind. In this study, they will receive one dose of the H5N1 vaccine at baseline.

Arm Title

Group 5 (Have Not Previously Received LAIV)

Arm Type

Experimental

Arm Description

Participants will have not previously received an LAIV of any kind. In this study, they will receive two doses of the H5N1 vaccine at baseline and Day 28.

Intervention Type

Biological

Intervention Name(s)

H5N1 Vaccine

Intervention Description

Vaccine will be administered intramuscularly (IM) in the deltoid muscle at baseline for participants in Groups 1-4 and at baseline and Day 28 for participants in Group 5.

Primary Outcome Measure Information:

Title

Characterize the kinetics and magnitude of the antibody response (measured by hemagglutination inhibition assay [HI] and microneutralization assay [MN]) to a single 45 micrograms dose of H5N1 vaccine

Time Frame

Measured through the 6 months following participants' last vaccination

Secondary Outcome Measure Information:

Title

Assess the reactogenicity of the H5N1 vaccine in previous recipients of LAIV

Description

Reactogenicity will be followed for 7 days; serious adverse events (SAEs) will be followed for 6 months after the last immunization.

Time Frame

Measured through the 6 months following participants' last vaccination

Title

Assess the immune response to the inactivated H5N1 vaccine (A/VN/1203/04)

Description

Time Frame

Measured through the 6 months following participants' last vaccination

10. Eligibility

Sex

All

Minimum Age & Unit of Time

22 Years

Maximum Age & Unit of Time

54 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: In general good health, without significant medical illness, physical examination findings, or significant laboratory abnormalities as determined by the investigator Available for the duration of the trial Willing to participate in the study as evidenced by signing the informed consent document Willing to allow storage and testing of laboratory samples for future research Received two doses of live attenuated H5N1 or H7N3 vaccine in a prior trial (Study Groups 1, 2, and 3) or LAIV and H5 naïve (Study Groups 4 and 5) Willing to forego seasonal LAIV for the duration of the trial (until 6 months after the last vaccination) Female participants must agree to use effective birth control methods for the duration of the study. More information on this criterion can be found in the protocol. Exclusion Criteria: Pregnant, as determined by a positive beta-human choriogonadotropin (HCG) test Currently breastfeeding Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urine testing Behavioral or cognitive impairment or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and cooperate with the study protocol Have medical, occupational, or family problems as a result of alcohol or illicit drug use during the 12 months prior to study entry Other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol History of anaphylaxis History of life-threatening reaction to prior influenza vaccine Current diagnosis of asthma or reactive airway disease (within the 2 years prior to study entry) Positive enzyme-linked immunosorbent assay (ELISA) and confirmatory Western blot tests for HIV-1 Positive ELISA and confirmatory test (e.g., recombinant immunoblot assay [RIBA]) for hepatitis C virus (HCV) Positive hepatitis B virus surface antigen (HBsAg) by ELISA Known immunodeficiency syndrome History of Guillain-Barré syndrome Use of chronic oral or intravenous administration (greater than or equal to 14 days) of immunosuppressive doses of steroids, i.e., prednisone greater than 10 mg per day, immunosuppressants or other immune-modifying drugs within 30 days of starting this study Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to study vaccination Receipt of blood or blood-derived products (including immunoglobulin) within 6 months prior to study vaccination Receipt of another investigational vaccine or drug within 30 days prior to study vaccination Allergy to eggs or egg products In addition to the above, participants in the H5 and LAIV-naïve groups must also not experience any of the following: Previous enrollment in an H5 influenza vaccine trial or in any study of an avian influenza (AI) vaccine Seropositive to the H5N1 influenza A virus (serum HI titer greater than 1:8) Previous receipt of FluMist or any intranasal live attenuated influenza vaccine

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kawsar R. Talaat, MD

Organizational Affiliation

Johns Hopkins Bloomberg School of Public Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centers for Immunization Research (CIR) - John Hopkins Bloomburg School of Public Health

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21205

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

18694338

Citation

Goji NA, Nolan C, Hill H, Wolff M, Noah DL, Williams TB, Rowe T, Treanor JJ. Immune responses of healthy subjects to a single dose of intramuscular inactivated influenza A/Vietnam/1203/2004 (H5N1) vaccine after priming with an antigenic variant. J Infect Dis. 2008 Sep 1;198(5):635-41. doi: 10.1086/590916.

Results Reference

background

PubMed Identifier

19416838

Citation

Galli G, Hancock K, Hoschler K, DeVos J, Praus M, Bardelli M, Malzone C, Castellino F, Gentile C, McNally T, Del Giudice G, Banzhoff A, Brauer V, Montomoli E, Zambon M, Katz J, Nicholson K, Stephenson I. Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine. Proc Natl Acad Sci U S A. 2009 May 12;106(19):7962-7. doi: 10.1073/pnas.0903181106. Epub 2009 Apr 27.

Results Reference

background

PubMed Identifier

24604819

Citation

Talaat KR, Luke CJ, Khurana S, Manischewitz J, King LR, McMahon BA, Karron RA, Lewis KD, Qin J, Follmann DA, Golding H, Neuzil KM, Subbarao K. A live attenuated influenza A(H5N1) vaccine induces long-term immunity in the absence of a primary antibody response. J Infect Dis. 2014 Jun 15;209(12):1860-9. doi: 10.1093/infdis/jiu123. Epub 2014 Mar 5. Erratum In: J Infect Dis. 2014 Dec 15;210(12):2021.

Results Reference

derived

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