Flublok or Fluzone With Advax-CpG55.2 or AF03

NCT ID: NCT03945825

Last Updated: 2025-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 241 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-10
• Study Completion Date: 2020-09-18

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.

Detailed Description

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. Subjects will be stratified by prior receipt of licensed, seasonal influenza vaccine (defined as receipt of at least one of the 2017/2018 and/or 2018/2019 influenza vaccines) and will be randomly assigned to 1 of 6 treatment arms to receive a single dose of one of the two seasonal 2018/2019 QIV vaccine formulations with or without one of the two adjuvants (Day 1). On approximately Day 90, each subject will receive a single dose of the seasonal 2019/2020 QIV. Groups 1, 2 and 3 will receive 2019/2020 Fluzone QIV and Groups 4, 5 and 6 will receive 2019/2020 Flublok QIV. 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. The secondary objectives of this study are: 1) to assess protocol specified adverse events of special interest (AESI), medically-attended adverse events (MAAEs), including new-onset chronic medical conditions (NOCMCs) and potentially immune-mediated medical conditions (PIMMCs) that occur after receipt of study product; 2) to assess the HAI, Neut and NAI ELLA responses to the 2019/2020 QIV strains prior to (Day 1) and approximately 28 days after vaccination with the 2019/2020 QIV in all study groups; 3) to assess the HAI antibody responses against heterologous influenza A/H1 and H3 strains from baseline (Day 1) to approximately Days 8, 29, 57, 90 and 118 after receipt of 2018/2019 Fluzone or Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 4) to assess NAI ELLA responses against heterologous N1 and N2 NA antigens from baseline (Day 1) to approximately Days 8, 29, 57, 90 and 118 after administration of 2018/2019 Fluzone with and without AF03 or Advax-CpG55.2 adjuvant; 5) to assess the influenza neutralizing (Neut) antibody titer responses against heterologous influenza A/H1 and H3 strains from baseline (Day 1) to approximately Days 8, 29, 57, 90 and 118 after administration of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 6) to assess the longitudinal kinetics and durability of the HAI, NAI, and Neut responses against the 2018/2019 QIV strains on approximately Days 8, 57, 90 and 118 following receipt of the 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant.

Conditions

Influenza; Influenza Immunisation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Group 1

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

Group Type: EXPERIMENTAL

Influenza Virus Quadrivalent Inactivated Vaccine

Intervention Type: BIOLOGICAL

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

Group 2

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

Group Type: EXPERIMENTAL

AF03

Intervention Type: DRUG

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

Influenza Virus Quadrivalent Inactivated Vaccine

Intervention Type: BIOLOGICAL

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

Group 3

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

Group Type: EXPERIMENTAL

Delta Inulin-CpG55.2

Intervention Type: BIOLOGICAL

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

Influenza Virus Quadrivalent Inactivated Vaccine

Intervention Type: BIOLOGICAL

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

Group 4

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

Group Type: EXPERIMENTAL

Quadrivalent Recombinant Seasonal Influenza Vaccine

Intervention Type: BIOLOGICAL

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

Group 5

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

Group Type: EXPERIMENTAL

AF03

Intervention Type: DRUG

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

Quadrivalent Recombinant Seasonal Influenza Vaccine

Intervention Type: BIOLOGICAL

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

Group 6

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

Group Type: EXPERIMENTAL

Delta Inulin-CpG55.2

Intervention Type: BIOLOGICAL

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

Quadrivalent Recombinant Seasonal Influenza Vaccine

Intervention Type: BIOLOGICAL

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

Interventions

AF03

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

Intervention Type: DRUG

Delta Inulin-CpG55.2

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

Intervention Type: BIOLOGICAL

Influenza Virus Quadrivalent Inactivated Vaccine

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

Intervention Type: BIOLOGICAL

Quadrivalent Recombinant Seasonal Influenza Vaccine

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

Intervention Type: BIOLOGICAL

Eligibility 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. Must agree to the collection of venous blood per protocol.

4. Are males or non-pregnant females, 18 to 45 years of age, inclusive at time of enrollment.

Exclusion Criteria

6. Oral temperature is less than 100.0 degrees Fahrenheit.

7. Pulse is 47 to 100 beats per minute, inclusive.

8. Systolic blood pressure is 85 to 140 mmHg, inclusive.

9. Diastolic blood pressure is 55 to 90 mmHg, inclusive.

10. 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.

11. 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").

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

13. 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.

14. Must agree to have residual specimens (i.e. residual/excess of per protocol specifications).

1. 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.

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

*Including acute, subacute, intermittent or chronic medical disease or condition 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 or recently active (12 months) 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 history of Guillain-Barré Syndrome (GBS).

10. Have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination.

11. Have a history of Potentially Immune-Mediated Medical Conditions (PIMMCs).

12. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.

13. Have any diagnosis, current or past, of schizophrenia, bipolar disease or other psychiatric diagnosis that may interfere* with subject compliance or safety evaluations.

*As determined by the site PI or appropriate sub-investigator.

14. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 5 years prior to study vaccination.

15. Have taken oral or parenteral (including intra-articular) corticosteroids of any dose within 30 days prior to study vaccination.

16. Have taken high-dose inhaled corticosteroids* within 30 days prior to study vaccination.

*High-dose defined as per age as using inhaled high-dose per reference chart in the National Heart, Lung and Blood Institute Guidelines for the Diagnosis and Management of Asthma (EPR-3) or other lists published in UPTODATE.

17. Received or plan to receive a licensed, live vaccine (excluding all licensed, seasonal LAIVs) within 30 days before or after the study vaccination.

18. Received or plan to receive a licensed, inactivated vaccine (excluding all licensed, seasonal IIVs) within 14 days before or after each study vaccination.

19. Have received any 2018/2019 seasonal influenza vaccine within the 6 months prior to enrollment.

20. Plans to receive any 2019/2020 seasonal influenza vaccine within approximately 90 days of receipt of the first study vaccination.

21. Have a known history of documented influenza infection within the past 6 months.

22. Received immunoglobulin or other blood products (except Rho D immunoglobulin) within 90 days prior to study vaccination.

23. Received an experimental agent* within 30 days prior to the study vaccination or expect to receive another experimental agent* during the trial-reporting period*.

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

**Other than from participation in this trial.

***Approximately 12 months after the first study vaccination.

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

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

**Approximately 12 months after the first study vaccination.

25. Female subjects who are breastfeeding or plan to breastfeed from the time of the first study vaccination through 30 days after the last study vaccination.

26. Plan to travel outside the US (continental US, Hawaii and Alaska) from the time of study vaccination through approximately 90 days after the first study vaccination.

27. Planning to donate blood within 4 months following first vaccination.

All study participants will be expected to receive the second study vaccination except under the circumstances listed below. The second study vaccination will not be administered to a subject if any of the following criteria are met:

• Meets the contraindication on the package insert to receipt of licensed influenza vaccine.
• As deemed necessary by the site principal investigator or appropriate sub-investigator for noncompliance or other reasons.
• Subject refusal of further study vaccination.
• Withdrawal of consent.
• Subject is lost to follow-up.
• Termination of this trial.
• New information becomes available that makes further participation unsafe.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Emory University School of Medicine

Atlanta, Georgia, United States

University of Iowa - Vaccine Research and Education Unit

Iowa City, Iowa, United States

University of Maryland Baltimore - School of Medicine - Medicine

Baltimore, Maryland, United States

Saint Louis University Center for Vaccine Development

St Louis, Missouri, United States

Duke Vaccine and Trials Unit

Durham, North Carolina, United States

Cincinnati Children's Hospital Medical Center Vaccine Research Center

Cincinnati, Ohio, United States

Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center

Nashville, Tennessee, United States

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 40107003 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

HHSN272201300018I

Identifier Type: -

Identifier Source: secondary_id

18-0011

Identifier Type: -

Identifier Source: org_study_id