Purpose

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

Eligibility

Eligible Ages
Between 18 Years and 45 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

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.
  5. Are in good health:
  6. As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical or psychiatric 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 or urgent care for condition, or invasive medical procedure and no adverse symptoms that need medical intervention such as medication change/supplemental oxygen). This includes no change in chronic prescription medication, dose or 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. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site PI or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening or treatment of continued symptoms of medical diagnosis or condition. Note: Low dose topical, corticosteroids as outlined in the Subject

Exclusion Criteria

as well as herbals, vitamins and supplements are permitted.

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 (ESR, WBC, Hgb, PLTs, ALT, T. Bili, AST, GGT, ALP serum lipase, serum amylase and 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 < / = 43U/L (women) or < / = 60 U/L (men); T Bili < / =1.20 mg/dl; Cr < 1.1mg/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).

Exclusion Criteria:

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.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Prevention
Masking
Triple (Participant, Care Provider, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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
  • Biological: Influenza Virus Quadrivalent Inactivated Vaccine
    2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval
Experimental
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
  • Drug: AF03
    A squalene-in-PBS emulsion stabilized by nonionic surfactants, sorbitan oleate and macrogol cetostearyl ether
  • Biological: Influenza Virus Quadrivalent Inactivated Vaccine
    2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval
Experimental
Group 3
0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Advax-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: Advax-CpG55.2
    A combination adjuvant supplied as two separate components, Advax (Sypharma Pty Ltd.) and CpG55.2 (Nikko Denka Avecia and Sypharma Pty Ltd)
  • Biological: Influenza Virus Quadrivalent Inactivated Vaccine
    2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval
Experimental
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
  • Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine
    2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval
Experimental
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
  • Drug: AF03
    A squalene-in-PBS emulsion stabilized by nonionic surfactants, sorbitan oleate and macrogol cetostearyl ether
  • Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine
    2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval
Experimental
Group 6
0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Advax-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: Advax-CpG55.2
    A combination adjuvant supplied as two separate components, Advax (Sypharma Pty Ltd.) and CpG55.2 (Nikko Denka Avecia and Sypharma Pty Ltd)
  • Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine
    2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval

More Details

NCT ID
NCT03945825
Status
Active, not recruiting
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Study Contact

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/H3 strains from baseline (Day 1) to approximately Days 8, 29, 57, 90, 118, 180 and 365 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, 118, 180 and 365 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/H3 strains from baseline (Day 1) to approximately Days 8, 29, 57, 90, 118, 180 and 365 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, 118, 180 and 365 following receipt of the 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.