Flublok or Fluzone With Advax-CpG55.2 or AF03

NCT03945825 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 18-0011HHSN272201300018I
• Study Type: interventional
• Target: 241
• Locations: 1 country
• Sites: 8

Brief Summary

This is a Phase I, randomized, double blinded, clinical trial in up to 240 males and non-pregnant females, 18-45 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of either the 2018/2019 seasonal Fluzone or Flublok Quadrivalent Influenza Vaccine (QIV) manufactured by Sanofi Pasteur (SP) given without adjuvant or with one of two adjuvant formulations, AF03 or Advax-CpG55.2. Eight Vaccine and Treatment Evaluation Unit (VTEU) sites will be included in the study. Study duration is approximately 18 months, and subject participation duration is 12 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 2) to assess the serum hemagglutination inhibition (HAI) antibody responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 3) to assess the serum neuraminidase inhibition antibody (NAI) responses by enzyme-linked lectin assay (ELLA) against NA antigens in the 2018/2019 QIV from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 4) to assess the influenza neutralizing (Neut) antibody titer responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax- CpG55.2 adjuvant.

Conditions

Influenza; Influenza Immunisation

Keywords

Immunogenicity; Influenza; Influenza Vaccine; Phase 1; Quadrivalent; Safety

Outcome Measures

Primary Outcomes (18)

• Number of Participants Reporting Local and Systemic Solicited Reactogenicity Events Post First Vaccination

  Local adverse events (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). 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 local or 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 Reporting Serious and Non-serious Adverse Events (AE) Through Day 29

  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 28 days after the first study vaccination while serious adverse events (SAEs) were collected at follow up visits through approximately 12 months after the first study vaccination. Adverse events were MedDRA coded and are summarized by MedDRA System Organ Class (SOC).

  Day 1 through Day 29

• 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 SAEs were reported from time of first study vaccination through approximately 12 months after the first study vaccination.

  Day 1 through Day 365

• Number of Participants Reporting Clinical Safety Laboratory Adverse Events (AEs) Post First Vaccination

  Laboratory parameters include white blood cells (WBC), hemoglobin, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, Gamma-Glutamyl Transferase (GGT), alkaline phosphatase (ALP), amylase, lipase, and creatinine. Thresholds for adverse events were considered WBC of 3.90 x10\^3/uL or lower or 10.60 x10\^3/uL or higher; hemoglobin 11.4 g/dL or lower (female) or 12.4 g/dL or lower (male); platelets 139 x10\^3/uL or below or 416 x10\^3/uL or greater when using EDTA tubes or platelets 124 x10\^3/uL or below or 550 x10\^3/uL or greater when using Citrate tubes; ALT 44 IU/L or greater (female) or 61 IU/L or greater (male); AST 37 IU/L or greater (female) or 44 IU/L or greater (male); bilirubin 1.30 mg/dL or greater; GGT 33 IU/L or greater (female) or 50 IU/L or greater (male); ALP 116 IU/L or greater; amylase 122 IU/L or greater; lipase 61 IU/L or greater; creatinine 1.1 mg/dL or greater (female) or 1.4 mg/dL or greater (male).

  Day 1 through Day 8

• Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains

  Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination.

  Day 1, Day 29

• Ratio of Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms

  Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

  Day 1, Day 29

• Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains

  Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. HAI seroconversion was defined as either a pre-vaccination titer \< 1:10 and a post-vaccination titer \>= 1:40 or a pre-vaccination titer \>= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.

  Day 29

• Percentage of Participants With Hemagglutination Inhibition (HAI) Titer of 1:40 or Greater Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains

  Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result.

  Day 1, Day 29

• Geometric Mean Fold Rise (GMFR) in Hemagglutination Inhibition (HAI) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains

  Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises from baseline were calculated as the Day 29 titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

  Day 29

• Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains

  Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination.

  Day 1, Day 29

• Ratio of Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms

  Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

  Day 1, Day 29

• Percentage of Participants Achieving Neuraminidase Inhibition (NAI) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains

  Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. NAI seroconversion was defined as \>4 four-fold rise in post-vaccination antibody titer at Day 29.

  Day 29

• Geometric Mean Fold Rise (GMFR) in Neuraminidase Inhibition (NAI) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains

  Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises from baseline were calculated as the Day 29 titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

  Day 29

• Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains

  Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination.

  Day 1, Day 29

• Ratio of Serum Neutralizing (Neut) Geometric Mean Titers (GMT) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms

  Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

  Day 1, Day 29

• Percentage of Participants Achieving Neutralizing (Neut) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains

  Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Neut seroconversion was defined as either a pre-vaccination titer \< 1:10 and a post-vaccination titer \>= 1:40 or a pre-vaccination titer \>= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.

  Day 29

• Percentage of Participants With Neutralizing (Neut) Titer of 1:40 or Greater Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains

  Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab.

  Day 1, Day 29

• Geometric Mean Fold Rise (GMFR) in Neutralizing (Neut) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains

  Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Fold-rises from baseline were calculated as the Day 29 titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

  Day 29

Secondary Outcomes (42)

• Number of Participants Reporting Protocol Specified Adverse Events of Special Interest (AESIs)

  Day 1 through Day 365

• Number of Participants Reporting Medically-Attended Adverse Events (MAAEs), New-Onset Chronic Medical Conditions (NOCMCs), and Potentially Immune-Mediated Medical Conditions (PIMMCs)

  Day 1 through Day 365

• Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains

  Day 90 through Day 118

• Ratio of Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms

  Day 90 through Day 118

• Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Titer Seroconversion Against 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains

  Day 118

Study Arms (6)

Group 1

EXPERIMENTAL

0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90, n=40

Biological: Influenza Virus Quadrivalent Inactivated Vaccine

Group 2

EXPERIMENTAL

0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90, n=40

Drug: AF03; Biological: Influenza Virus Quadrivalent Inactivated Vaccine

Group 3

EXPERIMENTAL

0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90, n=40

Biological: Delta Inulin-CpG55.2; Biological: Influenza Virus Quadrivalent Inactivated Vaccine

Group 4

EXPERIMENTAL

0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90, n=40

Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine

Group 5

EXPERIMENTAL

0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90, n=40

Drug: AF03; Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine

Group 6

EXPERIMENTAL

0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90, n=40

Biological: Delta Inulin-CpG55.2; Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine

Interventions

AF03 DRUG

A squalene-in-PBS emulsion stabilized by nonionic surfactants, sorbitan oleate and macrogol cetostearyl ether

Group 2; Group 5

Delta Inulin-CpG55.2 BIOLOGICAL

A combination adjuvant supplied as two separate components, Delta Inulin (Sypharma Pty Ltd.) and CpG55.2 (Nikko Denka Avecia and Sypharma Pty Ltd)

Group 3; Group 6

Influenza Virus Quadrivalent Inactivated Vaccine BIOLOGICAL

2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval

Group 1; Group 2; Group 3

Quadrivalent Recombinant Seasonal Influenza Vaccine BIOLOGICAL

2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval

Group 4; Group 5; Group 6

Eligibility Criteria

• Age: 18 Years - 45 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.
• Must agree to the collection of venous blood per protocol.
• Are males or non-pregnant females, 18 to 45 years of age, inclusive at time of enrollment.

You may not qualify if:

• Oral temperature is less than 100.0 degrees Fahrenheit.
• Pulse is 47 to 100 beats per minute, inclusive.
• Systolic blood pressure is 85 to 140 mmHg, inclusive.
• Diastolic blood pressure is 55 to 90 mmHg, inclusive.
• Screening laboratories (Erythrocyte Sedimentation Rate (ESR), White Blood Cells (WBC), Hemoglobin (Hgb), Platelets (PLTs), Alanine Aminotransferase (ALT), Total Bilirubin (T. Bili), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), Alkaline Phosphatase (ALP) serum lipase, serum amylase and Creatinine (Cr)) are within acceptable parameters\*.
• \*ESR must be below 30 mm/hr; WBC \>3.90 K/MM3 and \<10.60 K/MM3; Hgb \>/= 11.5 g/dl (women) or \>/= 12.5 g/dl (men); PLTs (EDTA) 140-415 K/MM3; PLTs (Citrate) 125-325 K/MM3 ALT \</= 43 U/L (women) or \</= 60 U/L (men); T Bili \</=1.20 mg/dl; Cr \< 1.1 mg/dl (women) or \< 1.4 mg/dl (men); AST 10-36 U/L (women) or 10-43 U/L (men); GGT 5--32 U/L (women) or 10-49 U/L (men); ALP 30-115 U/L (women) or 43-115 U/L (men); lipase 13-60 U/L; amylase (Total) 35-121 U/L, for subjects to qualify for randomization and vaccination.
• Women of childbearing potential\* must use an acceptable contraception method\*\* from at least 30 days before the first study vaccination until 60 days after the second study vaccination.
• \*Not sterilized via bilateral oophorectomy, tubal ligation/ 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 has passed since the last menses if menopausal.
• Includes non-male sexual relationships, full abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more and shown to be azoospermic prior to the subject receiving the study vaccination, barrier methods such as condoms or diaphragms/cervical cap with spermicide, effective 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 urine or serum pregnancy test within 24 hours prior to the first study vaccination.
• For a woman with potential to become pregnant, she understands that in the event of pregnancy during the study she will be approached to enroll in the Sanofi Pregnancy Registry.
• Must agree to have residual specimens (i.e. residual/excess of per protocol specifications).
• Have an acute illness\*, as determined by the site Principal Investigator (PI) 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 PI 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 PI or appropriate sub-investigator, is a contraindication to study participation\*.

Sponsors & Collaborators

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

Study Sites (8)

Emory University School of Medicine

Atlanta, Georgia, 30322-1014, United States

Location

University of Iowa - Vaccine Research and Education Unit

Iowa City, Iowa, 52242-2600, United States

Location

University of Maryland Baltimore - School of Medicine - Medicine

Baltimore, Maryland, 21201-1509, United States

Location

Saint Louis University Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

Duke Vaccine and Trials Unit

Durham, North Carolina, 27704, United States

Location

Cincinnati Children's Hospital Medical Center Vaccine Research Center

Cincinnati, Ohio, 45229-3039, United States

Location

Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center

Nashville, Tennessee, 37232-2573, United States

Location

Baylor College of Medicine

Houston, Texas, 77030-3411, United States

Location

Related Publications (1)

• Hegmann TE, Walter EB, Smith MJ, Campbell J, El Sahly HM, Whitaker JA, Creech CB, Ustyugova IV, Goncalvez AP, Pandey A, Alefantis T, Sridhar S, Honda-Okubo Y, Petrovsky N, Frey SE, Abate G, Paulsen G, Anderson EJ, Rostad CA, Rouphael N, Makhene M, Roberts PC, Tuyishimire B, Bryant C, Winokur P. A phase I study of the safety, reactogenicity and immunogenicity of two quadrivalent seasonal influenza vaccines (Fluzone(R) or Flublok(R)) with or without one of two adjuvants (AF03 or Advax-CpG55.2) in healthy adults 18-45 years of age. Vaccine. 2025 Apr 30;54:126991. doi: 10.1016/j.vaccine.2025.126991. Epub 2025 Mar 18.

  PMID: 40107003 DERIVED

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Patricia Winokur, MD
• Organization: University of Iowa Carver College of Medicine

patricia-winokur@uiowa.edu

319-384-1735

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2019
• First Posted: May 10, 2019
• Study Start: June 10, 2019
• Primary Completion: September 18, 2020
• Study Completion: September 18, 2020
• Last Updated: October 14, 2025
• Results First Posted: January 3, 2022

Record last verified: 2021-02-19

Locations

US (8)