Co-Administration of AS03 Adjuvanted A/H7N9 IIV With IIV4

• ClinicalTrials.gov Identifier: NCT03318315
• Recruitment Status: Completed
• First Posted: October 23, 2017
• Results First Posted: August 6, 2020
• Last Update Posted: August 6, 2020
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

This is a randomized, un-blinded, Phase II study in males and non-pregnant females, who are in good health, 19 to 64 years of age. This study is designed to assess the safety, reactogenicity, and immunogenicity of a pre-pandemic AS03 (GSK) adjuvanted 2017 monovalent inactivated influenza A/H7N9 vaccine, when two doses are administered 21 days apart either sequentially or simultaneously (within 15 minutes) with licensed seasonal influenza vaccine. Subjects will be randomized into one of three treatment groups. The study will enroll approximately 150 individuals who have no history of influenza A/H7N9 infection or prior receipt of an influenza virus H7 subtype vaccine. Study duration is approximately 16 months with subject participation duration of approximately 13 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity following sequential or simultaneous IM administration of 2 doses of AS03-adjuvanted 2017 H7N9 IIV and one dose of seasonal influenza vaccine (IIV4); 2) to assess the serum HAI and Neut antibody responses against A/H7N9 at approximately 21 days following receipt of two doses of AS03-adjuvanted 2017 H7N9 IIV administered IM approximately 21 days apart; 3) to assess the serum HAI and Neut antibody responses against the seasonal influenza strains at approximately 21 days following receipt of IIV4.

Condition or disease	Intervention/treatment	Phase
Avian Influenza; Influenza; Influenza Immunisation	Drug: AS03; Biological: Inactivated influenza H7N9 vaccine; Biological: Influenza Virus Quadrivalent Inactivated Vaccine; Other: Phosphate Buffered Saline (PBS) diluent	Phase 2

Detailed Description:

This is a randomized, un-blinded, Phase II study in males and non-pregnant females, who are in good health, 19 to 64 years of age. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of a pre-pandemic AS03 (GSK) adjuvanted 2017 monovalent inactivated influenza A/H7N9 vaccine (2017 H7N9 IIV) manufactured by Sanofi Pasteur (3.75 mcg of HA per dose with Phosphate Buffered Saline (PBS) diluent), when two doses are administered 21 days apart either sequentially or simultaneously (within 15 minutes) with licensed seasonal influenza vaccine. Subjects will be randomized into one of three treatment groups. Group 1 will receive two doses of AS03-adjuvanted 2017 H7N9 IIV, each dose administered IM approximately 21 days apart, and one dose of licensed seasonal IIV4 will be administered IM simultaneously (within 15 minutes) with the first dose of AS03 adjuvanted 2017 H7N9 IIV. Group 2 will receive one dose of IIV4 approximately 21 days prior to the IM administration of two doses of AS03-adjuvanted 2017 H7N9 IIV; each dose of AS03-adjuvanted 2017 H7N9 IIV will be given approximately 21 days apart. Group 3 will receive one dose IM of IIV4 as an un-blinded comparator. The study will enroll approximately 150 individuals who have no history of influenza A/H7N9 infection or prior receipt of an influenza virus H7 subtype vaccine. Study duration is approximately 16 months with subject participation duration of approximately 13 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity following sequential or simultaneous IM administration of 2 doses of AS03-adjuvanted 2017 H7N9 IIV and one dose of seasonal influenza vaccine (IIV4); 2) to assess the serum HAI and Neut antibody responses against A/H7N9 at approximately 21 days following receipt of two doses of AS03-adjuvanted 2017 H7N9 IIV administered IM approximately 21 days apart; 3) to assess the serum HAI and Neut antibody responses against the seasonal influenza strains at approximately 21 days following receipt of IIV4. The secondary objectives are: 1) to assess unsolicited non-SAEs following sequential or simultaneous IM administration of AS03-adjuvanted 2017 H7N9 IIV and seasonal influenza vaccine (IIV4); 2) to assess MAAEs, including NOCMCs and PIMMCs, following sequential or simultaneous IM administration of AS03-adjuvanted 2017 H7N9 IIV and IIV4; 3) to assess the HAI and Neut antibody responses at 21 days following receipt of 1 dose of AS03-adjuvanted 2017 H7N9 IIV.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 149 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase II Study in Healthy Adults (19-64 Years of Age) to Assess the Safety, Reactogenicity and Immunogenicity of Sequential or Simultaneous Intramuscular Administration of an AS03-adjuvanted A/H7N9 Inactivated Influenza Vaccine With Seasonal Influenza Vaccine
• Actual Study Start Date: February 20, 2018
• Actual Primary Completion Date: July 25, 2019
• Actual Study Completion Date: July 25, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1; 3.75 mcg HA per 0.5 mL dose of H7N9 vaccine in PBS diluent + GSK AS03 adjuvant and 0.5 ml dose of IIV4 vaccine, both administered intramuscularly within 15 minutes on day 1, and 3.75 mcg HA per 0.5 mL dose of H7N9 vaccine in PBS diluent + GSK AS03 adjuvant intramuscularly on day 22, n=60	Drug: AS03; AS03 oil-in-water emulsion adjuvant.; Biological: Inactivated influenza H7N9 vaccine; Monovalent 2017 H7N9 inactivated influenza vaccine; Biological: Influenza Virus Quadrivalent Inactivated Vaccine; A seasonal quadrivalent inactivated influenza vaccine (IIV4), prepared from influenza viruses propagated in embryonated chicken eggs, protecting against 2 influenza A subtypes (H1N1 and H3N2) and 2 influenza B subtypes (B Yamata lineage and B Victoria lineage).; Other: Phosphate Buffered Saline (PBS) diluent; Diluent for Adjuvanted 2017 Monovalent Inactivated Influenza A/H7N9 vaccine (2017 H7N9IIV)
Experimental: Group 2; 0.5 ml dose of IIV4 vaccine intramuscularly on day 1 and 3.75 mcg HA per 0.5 ml dose of H7N9 vaccine in PBS diluent + GSK AS03 adjuvant intramuscularly on day 22 and day 43, n=60	Drug: AS03; AS03 oil-in-water emulsion adjuvant.; Biological: Inactivated influenza H7N9 vaccine; Monovalent 2017 H7N9 inactivated influenza vaccine; Biological: Influenza Virus Quadrivalent Inactivated Vaccine; A seasonal quadrivalent inactivated influenza vaccine (IIV4), prepared from influenza viruses propagated in embryonated chicken eggs, protecting against 2 influenza A subtypes (H1N1 and H3N2) and 2 influenza B subtypes (B Yamata lineage and B Victoria lineage).; Other: Phosphate Buffered Saline (PBS) diluent; Diluent for Adjuvanted 2017 Monovalent Inactivated Influenza A/H7N9 vaccine (2017 H7N9IIV)
Active Comparator: Group 3; 0.5 ml dose of IIV4 vaccine intramuscularly on day 1, n=30	Biological: Influenza Virus Quadrivalent Inactivated Vaccine; A seasonal quadrivalent inactivated influenza vaccine (IIV4), prepared from influenza viruses propagated in embryonated chicken eggs, protecting against 2 influenza A subtypes (H1N1 and H3N2) and 2 influenza B subtypes (B Yamata lineage and B Victoria lineage).

Outcome Measures

Primary Outcome Measures :

1. Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies Against the 2017 H7N9 Inactivated Influenza Vaccine (IIV) Strain After Second H7N9 Vaccination [ Time Frame: 21 days after second dose of H7N9 ]
   Blood was collected for HAI assay at conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at 21 days after the second dose of H7N9, which is Day 43 for Group 1 and Day 64 for Group 2.
2. GMTs of Serum HAI Antibodies Against Each of the 2017 IIV4 Strains [ Time Frame: Day 22 ]
   Blood was collected for HAI assay at conducted with the IIV4 vaccine viruses as the antigens. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results.
3. GMTs of Serum Neutralizing Antibodies Against Each of the 2017 IIV4 Strains [ Time Frame: Day 22 ]
   Blood was collected for the serum neutralizing antibody assay conducted with the IIV4 vaccine viruses as the antigens. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results.
4. GMTs of Serum Neutralizing Antibodies Against the 2017 H7N9 IIV Strain After the Second H7N9 Vaccination [ Time Frame: 21 days after second dose of H7N9 ]
   Blood was collected for the serum neutralizing antibody assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at 21 days after second dose of H7N9, which is Day 43 for Group 1 and Day 64 for Group 2.
5. Number of Participants Reporting Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to Day 408 ]
   SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect. All events are included regardless of relationship to the study product.
6. Number of Participants Assessed With Clinical Safety Laboratory AEs After First Vaccination [ Time Frame: Day 8 ]
   Laboratory parameters include alanine aminotransferase (ALT), bilirubin, creatinine, hemoglobin, platelets and white blood cells (WBC). Thresholds for adverse events were considered as ALT 44 IU/L or greater (female) or 61 IU/L or greater (male); bilirubin 1.30 mg/dL or greater; creatinine 1.1 mg/dL or greater (female) or 1.4 mg/dL or greater (male); hemoglobin 11.4 g/dL or lower (female) or 12.4 g/dL or lower (male); platelets 139 x10^3/µL or below or 416 x10^3/µL or greater; or WBC or 3.9 x10^3/µL or lower or 10.6 x10^3/µL or higher.
7. Number of Participants Assessed With Clinical Safety Laboratory AEs After Second Vaccination [ Time Frame: Day 29 ]
   Laboratory parameters include alanine aminotransferase (ALT), bilirubin, creatinine, hemoglobin, platelets and white blood cells (WBC). Thresholds for adverse events were considered as ALT 44 IU/L or greater (female) or 61 IU/L or greater (male); bilirubin 1.30 mg/dL or greater; creatinine 1.1 mg/dL or greater (female) or 1.4 mg/dL or greater (male); hemoglobin 11.4 g/dL or lower (female) or 12.4 g/dL or lower (male); platelets 139 x10^3/µL or below or 416 x10^3/µL or greater; or WBC or 3.9 x10^3/µL or lower or 10.6 x10^3/µL or higher.
8. Number of Participants Assessed With Clinical Safety Laboratory AEs After Third Vaccination [ Time Frame: Day 50 ]
   Laboratory parameters include alanine aminotransferase (ALT), bilirubin, creatinine, hemoglobin, platelets and white blood cells (WBC). Thresholds for adverse events were considered as ALT 44 IU/L or greater (female) or 61 IU/L or greater (male); bilirubin 1.30 mg/dL or greater; creatinine 1.1 mg/dL or greater (female) or 1.4 mg/dL or greater (male); hemoglobin 11.4 g/dL or lower (female) or 12.4 g/dL or lower (male); platelets 139 x10^3/µL or below or 416 x10^3/µL or greater; or WBC or 3.9 x10^3/µL or lower or 10.6 x10^3/µL or higher.
9. Number of Participants Reporting Solicited Injection Site AEs After First Vaccination [ Time Frame: Day 1 up to day 8 ]
   Injection site AEs solicited on a memory aid provided to participants included . Participants are considered reporting the injection site AE if they reported mild or greater severity at any time during the 8 days following vaccination Pain, Tenderness, Itching/Pruritus, Ecchymosis/Bruising (functional grade based on interference with daily activities), Ecchymosis/Bruising (any measured value >0mm), Erythema/Redness (functional grade), Erythema/ Redness (any measured value >0mm), Induration/Swelling (functional grade), and Induration/Swelling (measurement grade)
10. Number of Participants Reporting Solicited Injection Site AEs After Second Vaccination [ Time Frame: Day 22 up to day 29 ]
    Injection site AEs solicited on a memory aid provided to participants included . Participants are considered reporting the injection site AE if they reported mild or greater severity at any time during the 8 days following vaccination Pain, Tenderness, Itching/Pruritus, Ecchymosis/Bruising (functional grade based on interference with daily activities), Ecchymosis/Bruising (any measured value >0mm), Erythema/Redness (functional grade), Erythema/ Redness (any measured value >0mm), Induration/Swelling (functional grade), and Induration/Swelling (measurement grade)
11. Number of Participants Reporting Solicited Injection Site AEs After Third Vaccination [ Time Frame: Day 43 up to day 50 ]
    Injection site AEs solicited on a memory aid provided to participants included . Participants are considered reporting the injection site AE if they reported mild or greater severity at any time during the 8 days following vaccination Pain, Tenderness, Itching/Pruritus, Ecchymosis/Bruising (functional grade based on interference with daily activities), Ecchymosis/Bruising (any measured value >0mm), Erythema/Redness (functional grade), Erythema/ Redness (any measured value >0mm), Induration/Swelling (functional grade), and Induration/Swelling (measurement grade)
12. Occurrence of Study Vaccine-related SAEs [ Time Frame: Day 1 up to day 408 ]
    SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect. Events are included if deemed by the investigator to be related to the study product.
13. Number of Participants Reporting Solicited Systemic AEs After First Vaccination [ Time Frame: Day 1 up to day 8 ]
    Systemic AEs solicited on a memory aid provided to participants included Elevated Oral Temperature, Feverishness, Fatigue, Malaise, Myalgia, Arthralgia, Headache, and Nausea. Participants are considered reporting the systemic AE if they reported mild or greater severity at any time during the 8 days following vaccination.
14. Number of Participating Reporting Solicited Systemic AEs After Second Vaccination [ Time Frame: Day 22 up to day 29 ]
    Systemic AEs solicited on a memory aid provided to participants included Elevated Oral Temperature, Feverishness, Fatigue, Malaise, Myalgia, Arthralgia, Headache, and Nausea. Participants are considered reporting the systemic AE if they reported mild or greater severity at any time during the 8 days following vaccination.
15. Number of Participants Reporting Solicited Systemic AEs After Third Vaccination [ Time Frame: Day 43 up to day 50 ]
    Systemic AEs solicited on a memory aid provided to participants included Elevated Oral Temperature, Feverishness, Fatigue, Malaise, Myalgia, Arthralgia, Headache, and Nausea. Participants are considered reporting the systemic AE if they reported mild or greater severity at any time during the 8 days following vaccination.
16. Percentage of Participants Achieving HAI Seroconversion Against 2017 H7N9 Study Vaccine After Second H7N9 Vaccination [ Time Frame: 21 days after second dose of H7N9 ]
    Blood was collected for the HAI assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as HAI pre-vaccination titer <1:10 and post-vaccination titer = / >1:40 or pre-vaccination titer 1:10 or greater and min. 4-fold rise in post-vaccination antibody titer. 21 days after second dose of H7N9 is Day 22 for Group 1 and Day 43 for Group 2.
17. Percentage of Participants Achieving Neutralizing Antibody Seroconversion Against 2017 H7N9 Study Vaccine After Second H7N9 Vaccination [ Time Frame: 21 days after second dose of H7N9 ]
    Blood was collected for the serum neutralizing antibody assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as neutralizing antibody pre-vaccination titer <1:10 and post-vaccination titer 1:40 or greater, or pre-vaccination titer 1:10 or greater and minimum 4-fold rise in post-vaccination antibody titer. 21 days after second dose of H7N9 is Day 22 for Group 1 and Day 43 for Group 2.
18. Percentage of Participants Achieving HAI Seroconversion Against Each of the Study IIV4 Strains [ Time Frame: Day 22 ]
    Blood was collected for the HAI assay conducted with the IIV4 vaccine viruses as the antigens. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as HAI pre-vaccination titer <1:10 and post-vaccination titer = / >1:40 or pre-vaccination titer 1:10 or greater and min. 4-fold rise in post-vaccination antibody titer.
19. Percentage of Participants With HAI Antibody Titer of 1:40 or Greater Against Each of the Study IIV4 Strains [ Time Frame: Day 22 ]
    Blood was collected for the HAI assay conducted with the IIV4 vaccine viruses as the antigens. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result.
20. Percentage of Participants With HAI Antibody Titer of 1:40 or Greater Against the Influenza 2017 H7N9 Study Vaccine Strain After Second H7N9 Vaccination [ Time Frame: 21 days after second dose of H7N9 ]
    Blood was collected for the HAI assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. 21 days after second dose of H7N9 is Day 43 for Group 1 and Day 64 for Group 2
21. Percentage of Participants With Neutralizing Antibody Titer of 1:40 or Greater Against Each of the Study IIV4 Strains [ Time Frame: Day 22 ]
    Blood was collected for the serum neutralizing antibody assay conducted with the IIV4 vaccine viruses as the antigens. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result.
22. Percentage of Participants With Neutralizing Antibody Titer of 1:40 or Greater Against the Influenza 2017 H7N9 Study Vaccine Strain After Second H7N9 Vaccination [ Time Frame: 21 days after second dose of H7N9 ]
    Blood was collected for the serum neutralizing antibody assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. 21 days after second dose of H7N9 is Day 43 for Group 1 and Day 64 for Group 2

Secondary Outcome Measures :

1. GMTs of Serum HAI Antibodies Against the Influenza 2017 H7N9 Vaccine Virus at Baseline [ Time Frame: Day 1 ]
   Blood was collected for HAI assay at conducted with the H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results.
2. GMTs of Serum HAI Antibodies Against the Influenza 2017 H7N9 Vaccine Virus After First H7N9 Vaccination [ Time Frame: 21 days after first dose of H7N9 ]
   Blood was collected for HAI assay at conducted with the H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results. 21 days after first dose of H7N9 is Day 22 for Group 1 and Day 43 for Group 2.
3. GMTs of Serum Neutralizing Antibodies Against the Influenza 2017 H7N9 Vaccine Virus at Baseline [ Time Frame: Day 1 ]
   Blood was collected for the serum neutralizing antibody assay at conducted with the H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results.
4. GMTs of Serum Neutralizing Antibodies Against the Influenza 2017 H7N9 Vaccine Virus After First H7N9 Vaccination [ Time Frame: 21 days after first dose of H7N9 ]
   Blood was collected for serum neutralizing antibody assay at conducted with the H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results. 21 days after first dose of H7N9 is Day 22 for Group 1 and Day 43 for Group 2.
5. Number of Participants Reporting Unsolicited Non-serious AEs After First Vaccination [ Time Frame: Approximately 21 days after first vaccination ]
   Adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Non-serious AEs were collected from participants at follow up visits through approximately 21 days after each vaccination. Adverse events were MedDRA coded and are summarized by MedDRA System Organ Class (SOC).
6. Number of Participants Reporting Unsolicited Non-serious AEs After Second Vaccination [ Time Frame: Approximately 21 days after second vaccination ]
   Adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Non-serious AEs were collected from participants at follow up visits through approximately 21 days after each vaccination. Adverse events were MedDRA coded and are summarized by MedDRA System Organ Class (SOC).
7. Number of Participants Reporting Unsolicited Non-serious AEs After Third Vaccination [ Time Frame: Approximately 21 days after third vaccination ]
   Adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Non-serious AEs were collected from participants at follow up visits through approximately 21 days after each vaccination. Adverse events were MedDRA coded and are summarized by MedDRA System Organ Class (SOC).
8. Number of Participants Reporting of Medically-Attended Adverse Events (MAAEs), Including New-Onset Chronic Medical Conditions (NOCMCs) and Potentially Immune-Mediated Medical Conditions (PIMMCs) [ Time Frame: Day 1 up to day 408 ]
   Participants were queried at each visit for the occurrence of medically-attended adverse events (MAAEs), including new-onset chronic medical conditions (NOCMCs) and potentially immune-mediated medical conditions (PIMMCs) throughout the duration of the study.
9. Number of Participants Reporting Study Vaccine-related Unsolicited Non-serious AEs After First Vaccination [ Time Frame: Approximately 21 days after first vaccination ]
   Adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Non-serious AEs were collected from participants at follow up visits through approximately 21 days after each vaccination. The site investigator determined vaccine related as "a reasonable possibility that the study product caused the AE. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the AE." Adverse events were MedDRA coded and are summarized by MedDRA System Organ Class (SOC).
10. Number of Participants Reporting Study Vaccine-related Unsolicited Non-serious AEs After Second Vaccination [ Time Frame: Approximately 21 days after second vaccination ]
    Adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Non-serious AEs were collected from participants at follow up visits through approximately 21 days after each vaccination. The site investigator determined vaccine related as "a reasonable possibility that the study product caused the AE. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the AE." Adverse events were MedDRA coded and are summarized by MedDRA System Organ Class (SOC).
11. Number of Participants Reporting Study Vaccine-related Unsolicited Non-serious AEs After Third Vaccination [ Time Frame: Approximately 21 days after third vaccination ]
    Adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Non-serious AEs were collected from participants at follow up visits through approximately 21 days after each vaccination. The site investigator determined vaccine related as "a reasonable possibility that the study product caused the AE. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the AE." Adverse events were MedDRA coded and are summarized by MedDRA System Organ Class (SOC).
12. Percentage of Participants Achieving HAI Antibody Seroconversion Against the 2017 H7N9 Vaccine Strain After First H7N9 Vaccination [ Time Frame: 21 days after first dose of H7N9 ]
    Blood was collected for HAI assay at conducted with the H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as HAI pre-vaccination titer <1:10 and post-vaccination titer 1:40 or greater, or pre-vaccination titer 1:10 or greater and min. 4-fold rise in post-vaccination antibody titer. 21 days after first dose of H7N9 is Day 22 for Group 1 and Day 43 for Group 2.
13. Percentage of Participants Achieving Neutralizing Antibody Seroconversion Against the 2017 H7N9 Vaccine Strain After First H7N9 Vaccination [ Time Frame: 21 days after first dose of H7N9 ]
    Blood was collected for serum neutralizing antibody assay at conducted with the H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as a pre-vaccination titer <1:10 and post-vaccination titer 1:40 or greater, or pre-vaccination titer 1:10 or greater and min. 4-fold rise in post-vaccination antibody titer. 21 days after first dose of H7N9 is Day 22 for Group 1 and Day 43 for Group 2.
14. Percentage of Participants Achieving Serum HAI Antibody Titers of 1:40 or Greater Against the Influenza 2017 H7N9 Vaccine Strain at Baseline [ Time Frame: Day 1 ]
    Blood was collected for HAI assay at conducted with the H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result.
15. Percentage of Participants Achieving Serum HAI Antibody Titers of 1:40 or Greater Against the Influenza 2017 H7N9 Vaccine Strain After First H7N9 Vaccination [ Time Frame: 21 days after first dose of H7N9 ]
    Blood was collected for serum neutralizing antibody assay at conducted with the H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. 21 days after first H7N9 vaccination was Day 22 for Group 1 and Day 43 for Group 2
16. Percentage of Participants Achieving Serum Neutralizing Antibody Titers of 1:40 or Greater Against the Influenza 2017 H7N9 Vaccine Strain at Baseline [ Time Frame: Day 1 ]
    Blood was collected for serum neutralizing antibody assay at conducted with the H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result.
17. Percentage of Participants Achieving Serum Neutralizing Antibody Titers of 1:40 or Greater Against the Influenza 2017 H7N9 Vaccine Strain After First H7N9 Vaccination [ Time Frame: 21 days after first dose of H7N9 ]
    Blood was collected for serum neutralizing antibody assay at conducted with the H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. 21 days after first H7N9 vaccination was Day 22 for Group 1 and Day 43 for Group 2

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Provide written informed consent prior to initiation of any study procedures.
2. Are able to understand and comply with planned study procedures and be available for all study visits.
3. Are males or non-pregnant females, 19 -64 years of age, inclusive.
4. Are in good health. - As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical diagnoses or conditions, defined as those that have been present for at least 90 days, which would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable for the last 60 days (no hospitalizations, Emergency Room (ER), or urgent care for condition and no adverse symptoms that need medical intervention such as medication change/supplemental oxygen). This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis or condition in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided there was no deterioration in the subject's chronic medical condition that necessitated a medication change, and there is no additional risk to the subject or interference with the evaluation of responses to study vaccination. Note: Topical, nasal, and inhaled medications (with the exception of inhaled corticosteroids as outlined in the Subject Exclusion Criteria), herbals, vitamins, and supplements are permitted.
5. Oral temperature is less than 100.0°F.
6. Pulse is 47 to 100 beats per minute (bpm), inclusive.
7. Systolic blood pressure is 85 to 150 mmHg, inclusive (subjects <65 years of age), 85 to 160 mmHg, inclusive (subjects = / > 65 years of age).
8. Diastolic blood pressure is 55 to 95 mmHg, inclusive.
9. ESR is less than 30 mm per hour.

10. Women of childbearing potential must use an acceptable contraception method from 30 days before first study vaccination until 60 days after last study vaccination.

    - Not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure® placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or <1 year of the last menses if menopausal.

    -- Includes non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving the first study vaccination, barrier methods such as condoms or diaphragms with spermicide or foam, effective intrauterine devices, NuvaRing®, and licensed hormonal methods such as implants, injectables, or oral contraceptives ("the pill").

11. Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to study vaccination.

Exclusion Criteria:

1. Have an acute illness, as determined by the site principal investigator or appropriate sub-investigator, within 72 hours prior to study vaccination.

   - An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site principal investigator or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.

2. Have any medical disease or condition that, in the opinion of the site principal investigator or appropriate sub-investigator, is a contraindication to study participation.

   - Including acute or chronic medical disease or condition, defined as persisting for at least 90 days, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial.

3. Have immunosuppression as a result of an underlying illness or treatment, a recent history or current use of immunosuppressive or immunomodulating disease therapy.
4. Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
5. Have known active neoplastic disease or a history of any hematologic malignancy. Non-melanoma, treated, skin cancers are permitted.
6. Have known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.
7. Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based adjuvants, or other components of the study vaccine.
8. Have a history of severe reactions following previous immunization with licensed or unlicensed influenza vaccines.
9. Have a personal or family history of narcolepsy.
10. Have a history of Guillian-Barre Syndrome (GBS).
11. Have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination.
12. Have a history of Potentially Immune-Mediated Medical Conditions (PIMMCs).
13. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.
14. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.
15. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 10 years prior to study vaccination.
16. Have taken oral or parenteral (including intra-articular) corticosteroids of any dose within 30 days prior to study vaccination.

17. Have taken high-dose inhaled corticosteroids within 30 days prior to each study vaccination.

    - High-dose defined per age as using inhaled high dose per reference chart https://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/quick-reference-html#estimated-comparative-daily-doses

18. Received a licensed live vaccine within 30 days prior to the first study vaccination, or plan to receive a licensed live vaccine within 30 days before or after each study vaccination.
19. Received or plan to receive a licensed, inactivated, vaccine (excluding all flu vaccines) within 14 days before or after each study vaccination.
20. Received or plan to receive the 2017-2018 inactivated seasonal flu vaccine prior to or during the clinical trial and for the remainder of the 2017-2018 season.
21. Received Ig or other blood products (with exception of Rho D Ig) within 90 days prior to each study vaccination.

22. Received an experimental agent within 30 days prior to the first study vaccination, or expect to receive an experimental agent during the 13-month trial-reporting period.

    - Including vaccine, drug, biologic, device, blood product, or medication.

    -- Other than from participation in this trial.

23. Are participating or plan to participate in another clinical trial with an interventional agent that will be received during the 13-month trial-reporting period.

    - Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication.

24. Received or plan to receive an influenza A/H7 vaccine or have a history of influenza A/H7 subtype infection.

    - And assigned to a group receiving influenza A/H7 vaccine.

25. Have traveled to mainland China and had substantial direct contact with live or freshly slaughtered poultry or pigeons within the past five years.

    - Substantial contact is defined as visited a poultry farm and/or a live poultry market.

26. Occupational exposure to or substantial direct physical contact with birds in the past year and through the 21 days after the last study vaccination.

    - Exposure to free range chickens in the yard is exclusionary. Casual contact with birds at petting zoos or county or state fairs, or having pet birds does not exclude subjects from study participation.

27. Female subjects who are breastfeeding or plan to breastfeed at any given time from the first study vaccination until 30 days after the last study vaccination.
28. Plan to travel outside the US (continental US, Hawaii, and Alaska) from enrollment through 21 days after the last study vaccination.

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham School of Medicine - Alabama Vaccine Research Clinic

Birmingham, Alabama, United States, 35294-2050

United States, Maryland

University of Maryland School of Medicine - Center for Vaccine Development - Baltimore

Baltimore, Maryland, United States, 21201-1509

United States, Ohio

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, United States, 45229-3039

United States, Tennessee

Vanderbilt University Medical Center - Infectious Diseases

Nashville, Tennessee, United States, 37232-0011

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):

Study Protocol  [PDF] September 18, 2018

Statistical Analysis Plan  [PDF] November 14, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ortiz JR, Spearman PW, Goepfert PA, Cross K, Buddy Creech C, Chen WH, Parker S, Overton ET, Dickey M, Logan HL, Wegel A, Neuzil KM. Safety and immunogenicity of monovalent H7N9 influenza vaccine with AS03 adjuvant given sequentially or simultaneously with a seasonal influenza vaccine: A randomized clinical trial. Vaccine. 2022 May 20;40(23):3253-3262. doi: 10.1016/j.vaccine.2022.03.055. Epub 2022 Apr 22.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT03318315
• Other Study ID Numbers: 17-0077; HHSN272201300022I
• First Posted: October 23, 2017
• Results First Posted: August 6, 2020
• Last Update Posted: August 6, 2020
• Last Verified: February 14, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

AS03-adjuvanted Inactivated Influenza Vaccine; Co-Administered; Healthy Adults; Immunogenicity; Inactivated Seasonal Influenza Vaccine; Phase II; Safety

Additional relevant MeSH terms:

Influenza, Human; Influenza in Birds; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs