Clinical trial NCT04451954: Study of Recombinant Influenza Vaccine Containing Different H3 Antigens Without or With Adjuvant in Healthy Adult Subjects
Official title: Safety and Immunogenicity of Quadrivalent Recombinant Influenza Vaccine Formulations Containing Different H3 Hemagglutinin Antigens Without or With Adjuvant in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza Immunisation
Healthy Volunteers
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2020-06-30
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: Study duration per participant is approximately 1 year

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with immediate adverse events
timeFrame: Within 30 minutes after vaccination
measure: Number of participants with solicited injection site or systemic reactions
timeFrame: From Day 0 to Day 7
measure: Number of participants with unsolicited adverse events
timeFrame: From Day 0 to Day 28
measure: Number of participants with serious adverse events
timeFrame: From Day 0 to Day 365
measure: Number of participants with adverse events of special interest
timeFrame: From Day 0 to Day 365
measure: Clinical safety laboratory test results
timeFrame: From Day 0 to Day 7
measure: HAI and SN antibody titers against influenza antigens in the quadrivalent RIV control vaccine
timeFrame: From Day 0 to Day 365
measure: Individual HAI and SN titers ratio against influenza antigens in the quadrivalent RIV control vaccine
timeFrame: From Day 0 to Day 90
measure: Number of participants with seroconversion to influenza antigens in the quadrivalent RIV control vaccine
timeFrame: From Day 0 to Day 28
measure: HAI Ab titer ≥ 40 [1/dil]
timeFrame: From Day 0 to Day 365
measure: 2-fold and 4-fold increase in SN titers
timeFrame: From Day 0 to Day 28
Secondary outcomes:
measure: HAI antibody titers against influenza H3 antigens not present in the vaccine formulations and the SN antibody titers against each of the H3 antigens
timeFrame: Day 0, Day 7, Day 28, Day 90, Day 180, and Day 365
measure: 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
timeFrame: From Day 0 to Day 90
measure: Number of participants with seroconversion to influenza H3 antigens not present in the vaccine formulations
timeFrame: Day 0 and Day 28
measure: 2-fold and 4-fold rise in SN antibody titers against each of the H3 antigens
timeFrame: Day 0, Day 7, Day 28, Day 90, Day 180, and Day 365
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Investigational Site Number 8400003
state: California
city: Melbourne
country: United States
facility: Investigational Site Number 8400002
state: Florida
city: Orlando
country: United States
facility: Investigational Site Number 8400004
state: Florida
city: Peoria
country: United States
facility: Investigational Site Number 8400001
state: Illinois
city: Rockville
country: United States
facility: Investigational Site Number 8400005
state: Maryland
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: