Clinical trial NCT03233217: Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine in Patients ≥65 Years
Official title: Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine Administered by Intramuscular or Subcutaneous Route in Participants Aged 65 Years and Older in Japan
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Influenza
Keywords: Influenza
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2017-07-28
Enrollment: 175
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Safety and tolerability was initially assessed in the first 10 participants in a smaller cohort (Cohort 1). Participants were randomized 1:1 into 2 groups in Cohort 1: QIV-HD by IM route (n=5) and QIV-HD by SC route (n=5).

After review of the local and systemic adverse events, the remaining 165 participants were enrolled (Cohort 2). Participants were randomized 1:1:1 into 3 groups in Cohort 2: QIV-HD by IM route (n=55), QIV-HD by SC route (n=55), and QIV-SD by SC route (n=55).
Primary purpose: PREVENTION

Brief summary: This phase I/II, randomized, modified double-blind, multi-center study assessed the safety and immunogenicity of a high-dose Quadrivalent influenza vaccine (QIV-HD) in older adults (greater than or equal to \[\>=\] 65 years).

Detailed description: This phase I/II, randomized, modified double-blind, multi-center study was conducted in 175 healthy Japanese adults aged 65 years and older to describe the safety profile and immune responses (geometric mean titers and seroconversion for the 4 common strains at 28 days post-vaccination) of the QIV-HD administered by intramuscular (IM) and subcutaneous (SC) methods. A local standard-dose Quadrivalent Influenza Vaccine (QIV-SD) administered by SC method served as a control arm.

Eligibility criteria: Inclusion Criteria:

* Aged \>= 65 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 study procedures.

Exclusion Criteria:

* 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 vaccination with live vaccines within the past 27 days preceding the study vaccination or any vaccination with inactivated vaccines within the past 6 days preceding the study vaccination, or planned receipt of any vaccine prior to Visit 3.
* Previous vaccination against influenza (in the preceding 6 months) with either the study vaccine or another vaccine.
* Receipt of immune globulins, blood or blood-derived products in the past 3 months.
* Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer 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).
* Known systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the study or to a vaccine containing any of the same substances.
* Thrombocytopenia or bleeding disorder, contraindicating IM vaccination based on Investigator's judgment.
* Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
* Alcohol 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, was at a stage where it might interfere with study conduct or completion.
* 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 (i.e., 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.
* Neoplastic disease or any hematologic malignancy (except localized skin or prostate cancer that was stable at the time of vaccination in the absence of therapy and participants who had a history of neoplastic disease and have been disease free for \>=5 years).
* Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature \>=37.5°Celsius). A prospective participant were not be included in the study until the condition had resolved or the febrile event had subsided.
* History of convulsions.

Primary outcomes:
measure: Number of Participants With Immediate Unsolicited Adverse Events (AE) After Vaccination
timeFrame: Within 30 minutes after vaccination
measure: Number of Participants With Solicited Injection Site and Systemic Reactions
timeFrame: Within 7 days after vaccination
measure: Number of Participants With Unsolicited Adverse Events After Vaccination
timeFrame: Within 28 days after vaccination
measure: Number of Participant With Serious Adverse Events (SAEs) After Vaccination
timeFrame: Up to 6 months after vaccination
Secondary outcomes:
measure: Cohort 2: Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With QIV-HD or QIV-SD
timeFrame: Day 0 (pre-vaccination) and Day 28 (post-vaccination)
measure: Cohort 2: Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With QIV-HD or QIV-SD
timeFrame: Day 0 (pre-vaccination) and Day 28 (post-vaccination)
measure: Cohort 2: Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With QIV-HD or QIV-SD
timeFrame: Day 28 (post-vaccination)
measure: Cohort 2: Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With QIV-HD or QIV-SD
timeFrame: Day 0 (pre-vaccination) and Day 28 (post-vaccination)
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: Sanofi Pasteur Investigational Site
city: Ōsaka
country: Japan
facility: Sanofi Pasteur Investigational Site
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Sanchez L, Matsuoka O, Inoue S, Inoue T, Meng Y, Nakama T, Kato K, Pandey A, Chang LJ. Immunogenicity and safety of high-dose quadrivalent influenza vaccine in Japanese adults >/=65 years of age: a randomized controlled clinical trial. Hum Vaccin Immunother. 2020 Apr 2;16(4):858-866. doi: 10.1080/21645515.2019.1677437. Epub 2019 Nov 19.