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

NCT03318315 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 17-0077HHSN272201300022I
• Study Type: interventional
• Target: 149
• Locations: 1 country
• Sites: 4

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.

Conditions

Avian Influenza; Influenza; Influenza Immunisation

Keywords

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

Outcome Measures

Primary Outcomes (22)

• Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies Against the 2017 H7N9 Inactivated Influenza Vaccine (IIV) Strain After Second H7N9 Vaccination

  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.

  21 days after second dose of H7N9

• GMTs of Serum HAI Antibodies Against Each of the 2017 IIV4 Strains

  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.

  Day 22

• GMTs of Serum Neutralizing Antibodies Against Each of the 2017 IIV4 Strains

  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.

  Day 22

• GMTs of Serum Neutralizing Antibodies Against the 2017 H7N9 IIV Strain After the Second H7N9 Vaccination

  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.

  21 days after second dose of H7N9

• Number of Participants Reporting Serious Adverse Events (SAEs)

  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.

  Day 1 up to Day 408

• Number of Participants Assessed With Clinical Safety Laboratory AEs After First Vaccination

  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.

  Day 8

• Number of Participants Assessed With Clinical Safety Laboratory AEs After Second Vaccination

  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.

  Day 29

• Number of Participants Assessed With Clinical Safety Laboratory AEs After Third Vaccination

  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.

  Day 50

• Number of Participants Reporting Solicited Injection Site AEs After First Vaccination

  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)

  Day 1 up to day 8

• Number of Participants Reporting Solicited Injection Site AEs After Second Vaccination

  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)

  Day 22 up to day 29

• Number of Participants Reporting Solicited Injection Site AEs After Third Vaccination

  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)

  Day 43 up to day 50

• Occurrence of Study Vaccine-related SAEs

  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.

  Day 1 up to day 408

• Number of Participants Reporting Solicited Systemic AEs After First Vaccination

  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.

  Day 1 up to day 8

• Number of Participating Reporting Solicited Systemic AEs After Second Vaccination

  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.

  Day 22 up to day 29

• Number of Participants Reporting Solicited Systemic AEs After Third Vaccination

  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.

  Day 43 up to day 50

• Percentage of Participants Achieving HAI Seroconversion Against 2017 H7N9 Study Vaccine After Second H7N9 Vaccination

  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.

  21 days after second dose of H7N9

• Percentage of Participants Achieving Neutralizing Antibody Seroconversion Against 2017 H7N9 Study Vaccine After Second H7N9 Vaccination

  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.

  21 days after second dose of H7N9

• Percentage of Participants Achieving HAI Seroconversion Against Each of the Study IIV4 Strains

  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.

  Day 22

• Percentage of Participants With HAI Antibody Titer of 1:40 or Greater Against Each of the Study IIV4 Strains

  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.

  Day 22

• Percentage of Participants With HAI Antibody Titer of 1:40 or Greater Against the Influenza 2017 H7N9 Study Vaccine Strain After Second H7N9 Vaccination

  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 days after second dose of H7N9

• Percentage of Participants With Neutralizing Antibody Titer of 1:40 or Greater Against Each of the Study IIV4 Strains

  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.

  Day 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

  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

  21 days after second dose of H7N9

Secondary Outcomes (17)

• GMTs of Serum HAI Antibodies Against the Influenza 2017 H7N9 Vaccine Virus at Baseline

  Day 1

• GMTs of Serum HAI Antibodies Against the Influenza 2017 H7N9 Vaccine Virus After First H7N9 Vaccination

  21 days after first dose of H7N9

• GMTs of Serum Neutralizing Antibodies Against the Influenza 2017 H7N9 Vaccine Virus at Baseline

  Day 1

• GMTs of Serum Neutralizing Antibodies Against the Influenza 2017 H7N9 Vaccine Virus After First H7N9 Vaccination

  21 days after first dose of H7N9

• Number of Participants Reporting Unsolicited Non-serious AEs After First Vaccination

  Approximately 21 days after first vaccination

Study Arms (3)

Group 1

EXPERIMENTAL

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; Biological: Inactivated influenza H7N9 vaccine; Biological: Influenza Virus Quadrivalent Inactivated Vaccine; Other: Phosphate Buffered Saline (PBS) diluent

Group 2

EXPERIMENTAL

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; Biological: Inactivated influenza H7N9 vaccine; Biological: Influenza Virus Quadrivalent Inactivated Vaccine; Other: Phosphate Buffered Saline (PBS) diluent

Group 3

ACTIVE COMPARATOR

0.5 ml dose of IIV4 vaccine intramuscularly on day 1, n=30

Biological: Influenza Virus Quadrivalent Inactivated Vaccine

Interventions

AS03 DRUG

AS03 oil-in-water emulsion adjuvant.

Group 1; Group 2

Inactivated influenza H7N9 vaccine BIOLOGICAL

Monovalent 2017 H7N9 inactivated influenza vaccine

Group 1; Group 2

Influenza Virus Quadrivalent Inactivated Vaccine BIOLOGICAL

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).

Group 1; Group 2; Group 3

Phosphate Buffered Saline (PBS) diluent OTHER

Diluent for Adjuvanted 2017 Monovalent Inactivated Influenza A/H7N9 vaccine (2017 H7N9IIV)

Group 1; Group 2

Eligibility Criteria

• Age: 19 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written informed consent prior to initiation of any study procedures.
• Are able to understand and comply with planned study procedures and be available for all study visits.
• Are males or non-pregnant females, 19 -64 years of age, inclusive.

You may not qualify if:

• Oral temperature is less than 100.0°F.
• Pulse is 47 to 100 beats per minute (bpm), inclusive.
• Systolic blood pressure is 85 to 150 mmHg, inclusive (subjects \<65 years of age), 85 to 160 mmHg, inclusive (subjects = / \> 65 years of age).
• Diastolic blood pressure is 55 to 95 mmHg, inclusive.
• ESR is less than 30 mm per hour.
• 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").
• Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to study vaccination.
• 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.
• 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.
• Have immunosuppression as a result of an underlying illness or treatment, a recent history or current use of immunosuppressive or immunomodulating disease therapy.
• Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (4)

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

Birmingham, Alabama, 35294-2050, United States

Location

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

Baltimore, Maryland, 21201-1509, United States

Location

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, 45229-3039, United States

Location

Vanderbilt University Medical Center - Infectious Diseases

Nashville, Tennessee, 37232-0011, United States

Location

Related Publications (2)

• El Sahly HM, Anderson EJ, Jackson LA, Neuzil KM, Atmar RL, Bernstein DI, Chen WH, Creech CB, Frey SE, Goepfert P, Meier J, Phadke V, Rouphael N, Rupp R, Stapleton JT, Spearman P, Walter EB, Winokur PL, Yildirim I, Williams TL, Oshinsky J, Coughlan L, Nijhuis H, Pasetti MF, Krammer F, Stadlbauer D, Nachbagauer R, Tsong R, Wegel A, Roberts PC. Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens. Vaccine. 2025 Feb 15;47:126689. doi: 10.1016/j.vaccine.2024.126689. Epub 2025 Jan 4.

  PMID: 39756216 DERIVED

• 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.

  PMID: 35465983 DERIVED

MeSH Terms

Conditions

Influenza in Birds; Influenza, Human

Condition Hierarchy (Ancestors)

Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Bird Diseases; Animal Diseases; Respiratory Tract Infections; Respiratory Tract Diseases

Results Point of Contact

• Title: Kathleen M. Neuzil, MD, MPH
• Organization: University of Maryland School of Medicine

kneuzil@som.umaryland.edu

410-706-5328

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2017
• First Posted: October 23, 2017
• Study Start: February 20, 2018
• Primary Completion: July 25, 2019
• Study Completion: July 25, 2019
• Last Updated: August 6, 2020
• Results First Posted: August 6, 2020

Record last verified: 2018-02-14

Locations

US (4)