Safety/Efficacy Study of Seqirus A/H7N9 IIV With or Without MF59(R) Adjuvant to Prevent Avian Influenza

NCT03682120 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 17-0076HHSN272201300021I
• Study Type: interventional
• Target: 372
• Locations: 1 country
• Sites: 7

Brief Summary

This is a randomized, double-blinded, Phase II study in healthy males and non-pregnant females, 18-64 years of age. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of a pre-pandemic 2017 monovalent inactivated influenza A/H7N9 virus vaccine (2017 H7N9 IIV) manufactured by Seqirus Inc (Seqirus) administered at different dosages (3.75 microgram mcg, 7.5 mcg and 15 mcg of hemagglutinin (HA) per dose) given with MF59(R) adjuvant manufactured by Seqirus Inc., or without adjuvant (15 mcg of HA per dose). Phosphate buffered saline (PBS) diluent manufactured by Patheon Manufacturing Services LLC will be used to achieve certain targeted doses. Approximately 371 subjects who are in good health and meet all eligibility criteria will be randomized into one of 4 study groups. The study will be conducted at up to 7 Vaccine and Treatment Unit (VTEU) sites and will last approximately 17 months, with subject participation duration of approximately 13 months. The Primary Objectives of the study are: 1) To assess the safety and reactogenicity following receipt of two doses of 2017 H7N9 IIV administered intramuscularly (IM) at different dosages approximately 21 days apart given with or without MF59(R) adjuvant; 2) To assess the serum hemagglutinin inhibition (HAI) and neutralizing (Neut) antibody responses approximately 21 days following receipt of two doses of 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with or without MF59(R) adjuvant.

Conditions

Avian Influenza; Influenza Immunisation

Keywords

A/H7N9; Healthy Adults; Immunogenicity; Influenza vaccine; MF59(R) adjuvant; Reactogenicity; Safety

Outcome Measures

Primary Outcomes (13)

• Geometric Mean Titers (GMT) of Serum Hemagglutinin Inhibition (HAI) Antibodies

  Blood was collected for HAI assay which was 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 (Day 43).

  Day 43

• Geometric Mean Titers (GMT) of Serum Neutralizing (Neut) Antibodies

  Blood was collected for Neutralizing assay which was 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 (Day 43).

  Day 43

• Number of Participants With Clinical Safety Laboratory Adverse Events

  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 1 through Day 8

• Number of Participants With Clinical Safety Laboratory Adverse Events

  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 22 to Day 29

• Number of Participants With Solicited Injection Site Reactogenicity Events

  Injection site AEs solicited on a memory aid provided to participants included 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 (any measured value \>0mm). Participants are considered reporting the injection site AE if they reported mild or greater severity at any time during the 8 days at or following the first vaccination.

  Day 1 through Day 8

• Number of Participants With Solicited Injection Site Reactogenicity Events

  Injection site AEs solicited on a memory aid provided to participants included 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 (any measured value \>0mm). Participants are considered reporting the injection site AE if they reported mild or greater severity at any time during the 8 days at or following the second vaccination.

  Day 22 through Day 29

• Number of Participants With Study Vaccine-related 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. Events are included if deemed by the investigator to be related to the study product.

  Day 1 through Day 387

• Number of Participants With Systemic Reactogenicity Events

  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 at or following the first vaccination.

  Day 1 through Day 8

• Number of Participants With Systemic Reactogenicity Events

  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 at or following the second vaccination.

  Day 22 through Day 29

• Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Antibody Titer of 1:40 or Greater

  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. The percentage of participants with HAI titer \>= 1:40 was calculated for each study group from the available results at 21 days after second dose of H7N9 (Day 43).

  Day 43

• Percentage of Participants Achieving Neutralizing (Neut) Antibody Titers of 1:40 or Greater

  Blood was collected for the Neutralizing 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 percentage of participants with Neut titer \>= 1:40 was calculated for each study group from the available results at 21 days after second dose of H7N9 (Day 43).

  Day 43

• Percentage of Participants Achieving Seroconversion Defined by Hemagglutination Inhibition (HAI) Antibodies

  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 and minimum 4-fold rise in post-vaccination antibody titer. 21 days after second dose of H7N9 is Day 43.

  Day 43

• Percentage of Participants Achieving Seroconversion Defined by Neutralizing (Neut) Antibodies

  Blood was collected for the Neutralizing 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 Neut pre-vaccination titer \<1:10 and post-vaccination titer \>= 1:40 or pre-vaccination titer \>= 1:10 and minimum 4-fold rise in post-vaccination antibody titer. 21 days after second dose of H7N9 is Day 43.

  Day 43

Secondary Outcomes (28)

• Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies

  Day 1

• Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies

  Day 8

• Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies

  Day 22

• Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies

  Day 29

• Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Antibodies

  Day 1

Study Arms (4)

Arm 1

EXPERIMENTAL

3.75 mcg per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + MF59(R) adjuvant administered intramuscularly on Day 1 and Day 22. Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. N=106

Biological: A/H7N9; Drug: MF59; Other: Phosphate Buffered Saline (PBS) diluent

Arm 2

EXPERIMENTAL

7.5 mcg per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + MF59(R) adjuvant administered intramuscularly on Day 1 and Day 22. Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. N=106

Biological: A/H7N9; Drug: MF59; Other: Phosphate Buffered Saline (PBS) diluent

Arm 3

EXPERIMENTAL

15 mcg per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + MF59(R) adjuvant administered intramuscularly on Day 1 and Day 22. Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. N=106

Biological: A/H7N9; Drug: MF59; Other: Phosphate Buffered Saline (PBS) diluent

Arm 4

EXPERIMENTAL

15 mcg per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) unadjuvanted administered intramuscularly on Day 1 and Day 22. Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. N=53

Biological: A/H7N9; Other: Phosphate Buffered Saline (PBS) diluent

Interventions

A/H7N9 BIOLOGICAL

Monovalent inactivated, "subunit" influenza virus vaccine containing the HA and NA from influenza A/Hong Kong/125/2017 (H7N9) and the PB2, PB1, PA, NP, M and NS genes from A/Puerto Rico/8/1934 (H1N1).

Arm 1; Arm 2; Arm 3; Arm 4

MF59 DRUG

Microfluoridized adjuvant 59 (MF59) is an oil-in-water emulsion.

Arm 1; Arm 2; Arm 3

Phosphate Buffered Saline (PBS) diluent OTHER

Diluent for Influenza Virus Vaccine.

Arm 1; Arm 2; Arm 3; Arm 4

Eligibility Criteria

• Age: 18 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, 18-64 years of age, inclusive.
• Oral temperature is less than 100.0 degree Fahrenheit.
• Pulse is 47 to 100 beats per minute, inclusive.
• Systolic blood pressure is 85 to 150 millimeters of Mercury, inclusive.
• Diastolic blood pressure is 55 to 95 millimeters of Mercury, inclusive.
• Women of childbearing potential\* must agree to practice 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(R) 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 male or female condoms with spermicide or with the use of applied spermicide, intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables, or oral contraceptives ("the pill").
• Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to study vaccination.

You may not qualify if:

• Have an acute illness\*, as determined by the site Principal Investigatoor 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.
• Have known active neoplastic disease or a history of any hematologic malignancy. Non-melanoma, treated, skin cancers are permitted.
• Have known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.
• Have known hypersensitivity or allergy to eggs, egg or chicken protein, neomycin, kanamycin, formaldehyde, polysorbate 80, cetyltrimethylammonium bromide (CTAB), squalene-based adjuvants, or other components of the study vaccine.
• Have a history of severe reactions following previous immunization with licensed or unlicensed influenza vaccines.
• Have a history of Guillian-Barre Syndrome.
• Have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination.
• Have a history of Potentially Immune Mediated Medical Conditions (PIMMCs)
• Have a history of alcohol or drug abuse within 5 years prior to study vaccination.
• Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.

Sponsors & Collaborators

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

Study Sites (7)

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

Birmingham, Alabama, 35294-2050, United States

Location

Saint Louis University - Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, 45229-3039, United States

Location

Vanderbilt University Medical Center - Vanderbilt Institute for Clinical and Translational Research - Clinical Research Center (VICTR-CRC)

Nashville, Tennessee, 37232-0011, United States

Location

The University of Texas Medical Branch - Sealy Center for Vaccine Development (SCVD)

Galveston, Texas, 77555-5302, United States

Location

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, 77030-3411, United States

Location

Kaiser Permanente Washington Health Research Institute - Vaccines and Infectious Diseases

Seattle, Washington, 98101-1466, United States

Location

Related Publications (1)

• Frey SE, Brady R, Jackson L, Goepfert P, El Sahly HM, Atmar RL, Rupp R, Creech CB, Abate G, Paulsen G, Weiss J, Wegel A, Roberts PC. Safety and immunogenicity of ascending doses of influenza A(H7N9) inactivated vaccine with or without MF59(R). Vaccine. 2025 Feb 15;47:126702. doi: 10.1016/j.vaccine.2024.126702. Epub 2025 Jan 10.

  PMID: 39798434 DERIVED

MeSH Terms

Conditions

Influenza in Birds; Influenza, Human

Interventions

MF59 oil emulsion

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: Sharon Frey, MD
• Organization: St Louis University School of Medicine

sharon.frey@health.slu.edu

314-997-5500

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2018
• First Posted: September 24, 2018
• Study Start: November 2, 2018
• Primary Completion: April 30, 2020
• Study Completion: April 30, 2020
• Last Updated: May 17, 2021
• Results First Posted: May 17, 2021

Record last verified: 2018-09-13

Locations

US (7)