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Phase 1 N=241 Randomized Double-blind Prevention

Flublok or Fluzone With Advax-CpG55.2 or AF03

Influenza · Influenza Immunisation

Enrolled (actual)
241
Serious AEs
0.8%
Results posted
Jan 2022
Primary outcome: Primary: Number of Participants Reporting Local and Systemic Solicited Reactogenicity Events Post First Vaccination — 24; 25; 23; 23 Participants

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
AF03 (Drug); Delta Inulin-CpG55.2 (Biological); Influenza Virus Quadrivalent Inactivated Vaccine (Biological); Quadrivalent Recombinant Seasonal Influenza Vaccine (Biological)
Age
Adult · 18+ yrs
Sex
All
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Primary completion
Sep 2020

Outcome Measures

OutcomeResultp-value
PRIMARY
Number of Participants Reporting Local and Systemic Solicited Reactogenicity Events Post First Vaccination
24; 25; 23; 23; 18; 26
PRIMARY
Number of Participants Reporting Serious and Non-serious Adverse Events (AE) Through Day 29
12; 11; 8; 14; 10; 15
PRIMARY
Number of Participants Reporting Serious Adverse Events (SAEs)
0; 1; 0; 0; 0; 1
PRIMARY
Number of Participants Reporting Clinical Safety Laboratory Adverse Events (AEs) Post First Vaccination
6; 2; 3; 2; 3; 0
PRIMARY
Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
296.6; 582.8; 343.0; 398.7; 469.4; 347.5
PRIMARY
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
2.0; 1.2; 1.2; 0.9; 2.1; 1.1
PRIMARY
Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
27; 35; 30; 29; 47; 43
PRIMARY
Percentage of Participants With Hemagglutination Inhibition (HAI) Titer of 1:40 or Greater Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
100; 100; 100; 100; 97; 100
PRIMARY
Geometric Mean Fold Rise (GMFR) in Hemagglutination Inhibition (HAI) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
2.6; 3.0; 3.5; 2.4; 3.6; 3.2
PRIMARY
Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
123.1; 116.4; 91.9; 140.9; 129.7; 105.9
PRIMARY
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
0.9; 0.7; 0.9; 0.8; 1.2; 1.2
PRIMARY
Percentage of Participants Achieving Neuraminidase Inhibition (NAI) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
27; 36; 36; 3; 0; 2
PRIMARY
Geometric Mean Fold Rise (GMFR) in Neuraminidase Inhibition (NAI) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
2.1; 2.5; 2.6; 1.0; 1.0; 1.0
PRIMARY
Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
140.6; 271.9; 154.0; 168.8; 210.6; 148.5
PRIMARY
Ratio of Serum Neutralizing (Neut) Geometric Mean Titers (GMT) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms
1.9; 1.1; 1.2; 0.9; 2.1; 1.3
PRIMARY
Percentage of Participants Achieving Neutralizing (Neut) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
10; 16; 20; 15; 11; 7
PRIMARY
Percentage of Participants With Neutralizing (Neut) Titer of 1:40 or Greater Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
95; 100; 95; 95; 95; 93
PRIMARY
Geometric Mean Fold Rise (GMFR) in Neutralizing (Neut) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
1.3; 1.8; 1.5; 1.1; 1.7; 1.3
SECONDARY
Number of Participants Reporting Protocol Specified Adverse Events of Special Interest (AESIs)
0; 0; 0; 0; 0; 0
SECONDARY
Number of Participants Reporting Medically-Attended Adverse Events (MAAEs), New-Onset Chronic Medical Conditions (NOCMCs), and Potentially Immune-Mediated Medical Conditions (PIMMCs)
9; 13; 7; 8; 7; 10
SECONDARY
Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains
325.5; 326.2; 234.7; 456.6; 408.2; 355.1
SECONDARY
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
1.0; 0.7; 0.9; 0.8; 0.9; 0.7
SECONDARY
Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Titer Seroconversion Against 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains
0; 0; 0; 6; 0; 6
SECONDARY
Percentage of Participants With Hemagglutination Inhibition (HAI) Titer of 1:40 or Greater Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains
100; 100; 92; 95; 95; 95
SECONDARY
Geometric Mean Fold Rise in Hemagglutination Inhibition (HAI) Titers Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains
1.1; 1.1; 1.2; 1.3; 1.3; 1.4
SECONDARY
Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms
90.1; 91.5; 72.4; 107.8; 111.8; 79.2
SECONDARY
Ratio of Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms for the Fluzone Study Arms
1.0; 0.8; 1.0; 0.7; 1.4; 1.0
SECONDARY
Percentage of Participants Achieving Neuraminidase Inhibition (NAI) Titer Seroconversion Against 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms
6; 0; 0; 8; 0; 0
SECONDARY
Geometric Mean Fold Rise (GMFR) in Neuraminidase Inhibition (NAI) Titers Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms
1.3; 1.2; 1.2; 1.4; 1.1; 1.3
SECONDARY
Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Titers Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains
3375.3; 3727.3; 2488.0; 4850.2; 5622.8; 3899.5
SECONDARY
Ratio of Serum Neutralizing (Neut) Geometric Mean Titers (GMT) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms
1.1; 0.7; 1.2; 0.8; 0.9; 0.7
SECONDARY
Percentage of Participants Achieving Neutralizing (Neut) Titer Seroconversion Against 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains
0; 0; 0; 9; 6; 3
SECONDARY
Geometric Mean Fold Rise (GMFR) in Neutralizing (Neut) Titers Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains
1.0; 1.0; 1.3; 1.4; 1.1; 1.3
SECONDARY
Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
296.6; 582.8; 343.0; 398.7; 469.4; 347.5
SECONDARY
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
2.0; 1.2; 1.2; 0.9; 2.1; 1.1
SECONDARY
Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
27; 35; 30; 29; 47; 43
SECONDARY
Percentage of Participants With Hemagglutination Inhibition (HAI) Titer of 1:40 or Greater Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
100; 100; 100; 100; 97; 100
SECONDARY
Geometric Mean Fold Rise (GMFR) in Hemagglutination Inhibition (HAI) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
2.6; 3.0; 3.5; 2.4; 3.6; 3.2
SECONDARY
Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms
441.2; 501.7; 394.0; 262.2; 260.4; 202.8
SECONDARY
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 for the Fluzone Study Arms
1.1; 0.9; 1.0; 0.8; 1.0; 0.7
SECONDARY
Percentage of Participants Achieving Neuraminidase Inhibition (NAI) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms
49; 62; 50; 20; 22; 24
SECONDARY
Geometric Mean Fold Rise (GMFR) in Neuraminidase Inhibition (NAI) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms
3.6; 4.3; 4.3; 2.0; 2.2; 2.4
SECONDARY
Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
140.6; 271.9; 154.0; 168.8; 210.6; 148.5
SECONDARY
Ratio of Serum Neutralizing (Neut) Geometric Mean Titers (GMT) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms
1.9; 1.1; 1.2; 0.9; 2.1; 1.3
SECONDARY
Percentage of Participants Achieving Neutralizing (Neut) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
10; 16; 20; 15; 11; 7
SECONDARY
Percentage of Participants With Neutralizing (Neut) Titer of 1:40 or Greater Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
95; 100; 95; 95; 95; 93
SECONDARY
Geometric Mean Fold Rise (GMFR) in Neutralizing (Neut) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
1.3; 1.8; 1.5; 1.1; 1.7; 1.3
SECONDARY
Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against Heterologous H1 and H3 Influenza Strains
59.5; 113.1; 70.3; 87.8; 78.6; 63.5
SECONDARY
Ratio of Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against Heterologous H1 and H3 Influenza Strains Between Adjuvanted and Unadjuvanted Study Arms
1.9; 1.2; 0.9; 0.7; 2.3; 1.6
SECONDARY
Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Titer Seroconversion Against Heterologous H1 and H3 Influenza Strains
44; 38; 33; 27; 50; 48
SECONDARY
Percentage of Participants With Hemagglutination Inhibition (HAI) Titer of 1:40 or Greater Against Heterologous H1 and H3 Influenza Strains
78; 78; 73; 71; 71; 69
SECONDARY
Geometric Mean Fold Rise (GMFR) in Hemagglutination Inhibition (HAI) Titers Against Heterologous H1 and H3 Influenza Strains
3.2; 3.9; 4.2; 3.0; 4.5; 4.7
SECONDARY
Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against Heterologous N1 and N2 Neuraminidase (NA) Antigens for the Fluzone Study Arms
16.6; 20.2; 14.5; 34.1; 49.6; 35.1
SECONDARY
Ratio of Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against Heterologous N1 and N2 Neuraminidase (NA) Antigens Between Adjuvanted and Unadjuvanted Study Arms for the Fluzone Study Arms
1.2; 0.9; 1.0; 0.8; 1.0; 0.9
SECONDARY
Percentage of Participants Achieving Neuraminidase Inhibition (NAI) Titer Seroconversion Against Heterologous N1 and N2 Neuraminidase (NA) Antigens for the Fluzone Study Arms
17; 27; 25; 24; 32; 38
SECONDARY
Geometric Mean Fold Rise (GMFR) in Neuraminidase Inhibition (NAI) Titers Against Heterologous N1 and N2 Neuraminidase (NA) Antigens for the Fluzone Study Arms
2.1; 2.5; 2.4; 2.2; 2.5; 2.3
SECONDARY
Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Titers Against Heterologous H1 and H3 Influenza Strains
293.5; 535.4; 348.3; 412.1; 388.6; 307.9
SECONDARY
Ratio of Serum Neutralizing (Neut) Geometric Mean Titers (GMT) Against Heterologous H1 and H3 Influenza Strains Between Adjuvanted and Unadjuvanted Study Arms
1.8; 1.2; 0.9; 0.7; 1.4; 1.2
SECONDARY
Percentage of Participants Achieving Neutralizing (Neut) Titer Seroconversion Against Heterologous H1 and H3 Influenza Strains
24; 32; 33; 27; 42; 45
SECONDARY
Geometric Mean Fold Rise (GMFR) in Neutralizing (Neut) Titers Against Heterologous H1 and H3 Influenza Strains
2.8; 4.3; 4.8; 2.9; 4.6; 4.6

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.

Eligibility Criteria

Inclusion Criteria

  • 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.
  • Are in good health*. *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.
  • 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 /= 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 preg
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03945825). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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