Study of Recombinant Influenza Vaccine Containing Different H3 Antigens Without or With Adjuvant in Healthy Adult Subjects (FBP00004)

Safety and Immunogenicity of Quadrivalent Recombinant Influenza Vaccine Formulations Containing Different H3 Hemagglutinin Antigens Without or With Adjuvant in Healthy Adult Subjects

The primary objectives of the study are:

• To describe the safety profile of the different formulations in all participants
• To describe the hemagglutinin inhibition (HAI) and seroneutralization (SN) antibody responses against hemagglutinin (H1, H3, B/Victoria, and B/Yamagata) antigens present in the control vaccine in all groups at all timepoints.

The secondary objectives are:

• To describe antigenic coverage in each group by assessing the HAI and SN antibody responses against a panel of H3 antigens (not present in any of the vaccine formulations).
• To describe SN antibody responses in each group against each of the H3 antigens.
• To compare H3 HAI and SN antibody responses for the groups with quadrivalent recombinant influenza vaccine (RIV) formulations with H3 antigens to those of the quadrivalent RIV control group.
• To compare the HAI and SN antibody responses for the groups with quadrivalent RIV formulation with adjuvant to the group without adjuvant.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Influenza Immunisation
• Intervention / Treatment: Biological: Quadrivalent RIV with H3 strain 1; Biological: Quadrivalent RIV with H3 strain 1 and adjuvant; Biological: Quadrivalent RIV with H3 strain 2; Biological: Quadrivalent RIV with H3 strain 2 and adjuvant; Biological: Quadrivalent RIV with 2018-2019 NH H3 strain; Biological: Quadrivalent RIV with 2018-2019 NH H3 strain and adjuvant

Detailed Description

Study duration per participant is approximately 1 year

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92108
      • Investigational Site Number 8400003
  • Florida
    • Melbourne, Florida, United States, 32934
      • Investigational Site Number 8400002
    • Orlando, Florida, United States, 32806
      • Investigational Site Number 8400004
  • Illinois
    • Peoria, Illinois, United States, 61614
      • Investigational Site Number 8400001
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Investigational Site Number 8400005

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria :

• Older adults: Aged 50 years and older on the day of inclusion Young adults: Aged 18 to 30 years on the day of inclusion
• Informed consent form has been signed and dated
• Able to attend all scheduled visits and to comply with all trial procedures

Exclusion criteria:

• Participant is pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 12 weeks postvaccination. To be considered of non-childbearing potential, a female must be premenarche, or postmenopausal for at least 1 year, or surgically sterile
• Participation at the time of study enrollment (or in the 4 weeks preceding the study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
• Receipt of any vaccine in the 4 weeks preceding the study vaccination or planned receipt of any vaccine in the 4 weeks following study vaccination
• Previous vaccination against influenza during either of the previous 2 influenza seasons (2018-2019 and 2019-2020) with any licensed or investigational influenza vaccine
• Receipt of immune globulins, blood, or blood-derived products in the past 3 months
• Known or suspected congenital or acquired immunodeficiency; immunosuppressive therapy (such as anticancer chemotherapy or radiation therapy, within the preceding 6 months); or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) or receipt of hydroxychloroquine within the preceding 4 weeks
• Dementia or any other cognitive condition at a stage that could interfere with following the trial procedures
• Have known active or recently active (12 months) neoplastic disease or a history of any hematologic malignancy
• History of influenza infection during either of the previous 2 influenza seasons (2018- 2019 or 2019-2020), confirmed by laboratory tests (including rapid tests) at that time
• History of laboratory confirmed coronavirus disease 2019 (COVID-19), confirmed with a nucleic acid amplification test on a respiratory specimen, or known exposure to severe acute respiratory syndrome coronavirus (SARS-CoV-2) positive confirmed close contact (eg, family member, housemate, daycare provider, aged parent requiring care), in the 30 days preceding vaccination, at the discretion of the investigator
• Self-reported or documented seropositivity for human immunodeficiency virus, hepatitis B, or hepatitis C
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances
• Have any diagnosis, current or past, of an autoimmune disease
• Thrombocytopenia or bleeding disorder, contraindicating intramuscular vaccination based on investigator's judgment
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Any change in chronic prescription medication or change in medication dose or dosage in the 60 days prior to enrollment
• Alcohol abuse or substance abuse that, in the opinion of the investigator, might interfere with the study conduct or completion
• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion
• Any current or past diagnosis of chronic pulmonary disease including asthma (history of childhood asthma is allowed), cystic fibrosis and chronic pulmonary obstructive disease
• Have taken a high-dose inhaled corticosteroid within 6 months prior to study vaccination
• Body mass index of 40 or higher
• Any current or past diagnosis of cardiac disease (eg, coronary artery disease, heart failure, or valvular heart disease [mild mitral valve prolapse allowed]). Participants with isolated primary (essential) hypertension are allowed
• Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (oral temperature ≥100.4 F [≥38.0 C]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided
• Identified as an investigator or employee of the investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the investigator or employee with direct involvement in the proposed study
• Personal or family history of Guillain-Barré syndrome
• History of chronic kidney disease
• Current or past diagnosis of thyroid disease (eg, thyroiditis [including Hashimoto's thyroiditis], hyperthyroidism, and hypothyroidism)

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Quadrivalent RIV with H3 strain 1, without adjuvant; 1 injection of quadrivalent RIV containing H3 strain 1, without adjuvant, in participants ≥ 50 years old	Biological: Quadrivalent RIV with H3 strain 1; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
Experimental: Group 2: Quadrivalent RIV with H3 strain 1, with adjuvant; 1 injection of quadrivalent RIV containing H3 strain 1, with adjuvant, in participants ≥ 50 years old	Biological: Quadrivalent RIV with H3 strain 1 and adjuvant; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
Experimental: Group 3: Quadrivalent RIV with H3 strain 2, without adjuvant; 1 injection of quadrivalent RIV containing H3 strain 2, without adjuvant, in participants ≥ 50 years old	Biological: Quadrivalent RIV with H3 strain 2; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
Experimental: Group 4: Quadrivalent RIV with H3 strain 2, with adjuvant; 1 injection of quadrivalent RIV containing H3 strain 2, with adjuvant, in participants ≥ 50 years old	Biological: Quadrivalent RIV with H3 strain 2 and adjuvant; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
Active Comparator: Group 5: Quadrivalent RIV Control, without adjuvant; 1 injection of quadrivalent RIV containing 2018-19 Northern Hemisphere (NH) recommended H3 strain, without adjuvant, in participants ≥ 50 years old	Biological: Quadrivalent RIV with 2018-2019 NH H3 strain; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
Active Comparator: Group 6: Quadrivalent RIV Control, with adjuvant; 1 injection of quadrivalent RIV containing 2018-19 NH recommended H3 strain, with adjuvant, in participants ≥ 50 years old	Biological: Quadrivalent RIV with 2018-2019 NH H3 strain and adjuvant; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
Active Comparator: Group 7: Quadrivalent RIV Control, without adjuvant; 1 injection of quadrivalent RIV containing 2018-19 NH recommended H3 strain, without adjuvant, in participants 18-30 years old	Biological: Quadrivalent RIV with 2018-2019 NH H3 strain; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with immediate adverse events	Immediate adverse events are unsolicited systemic adverse events reported in the 30 minutes after vaccination	Within 30 minutes after vaccination
Number of participants with solicited injection site or systemic reactions	Solicited injection site reactions: injection site pain, erythema, swelling, induration and bruising; solicited systemic reactions: fever, headache, malaise, and myalgia	From Day 0 to Day 7
Number of participants with unsolicited adverse events	Unsolicited (spontaneously reported) adverse events not not fulfilling criteria for solicited reactions	From Day 0 to Day 28
Number of participants with serious adverse events	Serious adverse events are collected throughout the study	From Day 0 to Day 365
Number of participants with adverse events of special interest	Adverse events of special interest are collected throughout the study	From Day 0 to Day 365
Clinical safety laboratory test results	Laboratory tests include complete blood count (CBC), platelet count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, serum creatinine, serum lipase, and serum amylase)	From Day 0 to Day 7
HAI and SN antibody titers against influenza antigens in the quadrivalent RIV control vaccine	Influenza antibody titers are measured by HAI and SN assays	From Day 0 to Day 365
Individual HAI and SN titers ratio against influenza antigens in the quadrivalent RIV control vaccine	Titers ratio is calculated for the following time points: Day 7/Day 0, Day 28/Day 0, and Day 90/Day 0	From Day 0 to Day 90
Number of participants with seroconversion to influenza antigens in the quadrivalent RIV control vaccine	Seroconversion is defined as HAI antibody titer < 10 [1/dil] at Day 0 and post-injection titer ≥ 40 [1/dil] at Day 28, or titer ≥ 10 [1/dil] at Day 0 and a ≥ 4-fold increase in titer [1/dil] at Day 28)	From Day 0 to Day 28
HAI Ab titer ≥ 40 [1/dil]	Influenza vaccine antibody titers are measured by HAI assay	From Day 0 to Day 365
2-fold and 4-fold increase in SN titers	Influenza vaccine antibody titers are measured by SN assay	From Day 0 to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HAI antibody titers against influenza H3 antigens not present in the vaccine formulations and the SN antibody titers against each of the H3 antigens	Influenza vaccine antibody titers are measured by HAI and SN assays	Day 0, Day 7, Day 28, Day 90, Day 180, and Day 365
Individual HAI titer ratios against influenza H3 antigens not present in the vaccine formulations and individual SN titer ratio against each of the H3 antigens	Titer ratio is calculated for the following time points: Day 7/Day 0, Day 28/Day 0, Day 90/Day 0	From Day 0 to Day 90
Number of participants with seroconversion to influenza H3 antigens not present in the vaccine formulations	Seroconversion is defined as HAI antibody titer < 10 [1/dil] at Day 0 and post-injection titer ≥ 40 [1/dil] at Day 28, or titer ≥ 10 [1/dil] at Day 0 and a ≥ 4-fold increase in titer [1/dil] at Day 28)	Day 0 and Day 28
2-fold and 4-fold rise in SN antibody titers against each of the H3 antigens	Influenza vaccine antibody titers a are measured by SN assay	Day 0, Day 7, Day 28, Day 90, Day 180, and Day 365

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi Pasteur, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2020
• Primary Completion (Actual): September 20, 2021
• Study Completion (Actual): September 20, 2021

Study Registration Dates

• First Submitted: June 25, 2020
• First Submitted That Met QC Criteria: June 25, 2020
• First Posted (Actual): June 30, 2020

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 15, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: FBP00004; U1111-1239-0391 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No