A Phase 2a Randomized, Observer-blind, Dose-finding Study to Evaluate the Immunogenicity and Safety of mRNA-based Multivalent Seasonal Influenza Vaccine Candidates in Adults 18 Years of Age and Older
Overview
- Phase
- Phase 2
- Intervention
- F2G22B/DL001Z
- Conditions
- Influenza, Human
- Sponsor
- GlaxoSmithKline
- Enrollment
- 845
- Locations
- 18
- Primary Endpoint
- Part 1 YA: Geometric Mean Titer (GMT) of Antigen 1 Antibody Titer
- Status
- Completed
- Last Updated
- last month
Overview
Brief Summary
The purpose of this study is to assess the safety and immune response of GlaxoSmithKlines (GSK) messenger RNA (mRNA)-based multivalent vaccine (GSK4382276A) candidate against influenza, administered in healthy younger adults (YA) and older adults (OA).
Investigators
Eligibility Criteria
Inclusion Criteria
- •A male or female between and including 18 and 85 years of age (YAs: 18-64; OAs: 65-85) at the time of the study intervention administration.
- •Healthy participants or medically stable patients as established by medical history and clinical examination. Participants with chronic medical conditions with or without specific treatment (e.g., chronic metabolic, cardiac, pulmonary, renal, hepatic, neurologic, and hematologic diseases) are allowed to participate in this study if considered by the investigator as medically stable. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during 3 months before enrolment.
- •Body mass index (BMI) \>=18 Kilograms per meter square (kg/m²) and less than or equal to (\<=) 35kg/m
- •Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits), independently or with the assistance of a caregiver.
- •Written informed consent obtained from the participant prior to performance of any study-specific procedure.
- •Female participants of non-childbearing potential may be enrolled in the clinical study.
- •Female participants of childbearing potential may be enrolled in the clinical study, if the participant:
- •Has practiced adequate contraception for 1 month prior to the study intervention administration, and
- •Has a negative pregnancy test within 24 hours prior to the study intervention administration, and
- •Has agreed to continue adequate contraception for at least 1 month after study intervention administration.
Exclusion Criteria
- •Participant tested positive for influenza by local health authority-approved testing methods within 180 days prior to Day
- •Current or past malignancy, unless completely resolved without sequelae for greater than (\>) 5 years before the study intervention administration (excluding effectively treated basal cell skin cancer).
- •Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination (no laboratory testing required). HIV-infected individuals may be enrolled if they have been stable on antiretroviral therapy for the past 6 consecutive months, i.e., their treatment has not been modified, their cluster of differentiation 4 (CD4) cell count is \>= 200/ cubic millimeter (mm³) and their viral load has been undetectable (i.e., HIV-RNA lesser than (\<) 50 copies/milliliter \[mL\]) (based on medical records, no laboratory testing required).
- •Participants with a history of, or current suspicion of myocarditis, pericarditis, or idiopathic cardiomyopathy (including a history of myocarditis or pericarditis following vaccination with an mRNA COVID-19 vaccine), or presence of any medical condition that increases risk of myocarditis or pericarditis, including cocaine abuse, cardiomyopathy, endomyocardial fibrosis, hypereosinophilic syndrome, hypersensitivity myocarditis, eosinophilic granulomatosis with polyangiitis and persistent myocardial infection will be excluded from the study.
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention (including polyethylene glycol, egg proteins and aminoglycoside antibiotics).
- •Hypersensitivity to latex.
- •Recurrent history or uncontrolled neurological disorders or seizures, including Guillain-Barré syndrome and Bell's palsy, with the exception of febrile seizures during childhood.
- •Any history of dementia or any medical condition that moderately or severely impairs cognition.
- •Any condition that in the judgment of the investigator would make intramuscular injection unsafe.
- •Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the clinical study.
Arms & Interventions
Part 1 YA: Flu mRNA_1_Younger Adults (YA)
YA participants received a single dose of Flu mRNA study intervention F2G22B/DL001Z administered at Day 1.
Intervention: F2G22B/DL001Z
Part 1 YA: Flu mRNA_2_YA
YA participants received a single dose of Flu mRNA study intervention F2H23D/DL001Z-NH administered at Day 1.
Intervention: F2H23D/DL001Z-NH
Part 1 YA: Flu mRNA_3_YA
YA participants received a single dose of Flu mRNA study intervention F2H23B/DL001Z-NH administered at Day 1.
Intervention: F2H23B/DL001Z-NH
Part 1 YA: Flu mRNA_4_YA
YA participants received a single dose of Flu mRNA study intervention F2H23H/DL001Z administered at Day 1.
Intervention: F2H23H/DL001Z
Part 1 YA: Comparator_1_YA
YA participants received a single dose of Comparator 1 \[FDQ23A-NH (Flu D-QIV)\] administered at Day 1.
Intervention: FDQ23A-NH (Flu D-QIV)
Part 2 YA: Flu mRNA_9_YA
YA participants received a single dose of Flu mRNA study intervention GSK5800544A administered at Day 1.
Intervention: GSK5800544A
Part 2 YA: Comparator_2_YA
YA participants received a single dose of Comparator 2 (Flu D-TIV) administered at Day 1.
Intervention: Flu D-TIV
Part 1 OA: Flu mRNA_5_Older Adults (OA)
OA participants received a single dose of Flu mRNA study intervention F2H23B/DL001Z-NH administered at Day 1.
Intervention: F2H23B/DL001Z-NH
Part 1 OA: Flu mRNA_6_OA
OA participants received a single dose of Flu mRNA study intervention F2H23A/DL001Z-NH administered at Day 1.
Intervention: F2H23A/DL001Z-NH
Part 1 OA: Flu mRNA_7_OA
OA participants received a single dose of Flu mRNA study intervention F2H23H/DL001Z administered at Day 1.
Intervention: F2H23H/DL001Z
Part 1 OA: Flu mRNA_8_OA
OA participants received a single dose of Flu mRNA study intervention F2H23G/DL001Z administered at Day 1.
Intervention: F2H23G/DL001Z
Part 1 OA: Comparator_1_OA
OA participants received a single dose of Comparator 1 (Fluzone HD Quadrivalent) administered at Day 1.
Intervention: Fluzone HD Quadrivalent
Part 2 OA: Flu mRNA_10_OA
OA participants received a single dose of Flu mRNA study intervention GSK5800544A administered at Day 1.
Intervention: GSK5800544A
Part 2 OA: Comparator_2_OA
OA participants received a single dose of Comparator 2 (Fluzone HD) administered at Day 1.
Intervention: Fluzone HD
Outcomes
Primary Outcomes
Part 1 YA: Geometric Mean Titer (GMT) of Antigen 1 Antibody Titer
Time Frame: At Day 29
Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 2 YA: GMT of Antigen 1 Antibody Titer
Time Frame: At Day 29
Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 1 OA: GMT of Antigen 1 Antibody Titer
Time Frame: At Day 29
Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 2 OA: GMT of Antigen 1 Antibody Titer
Time Frame: At Day 29
Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 1 YA: Geometric Mean Increase (GMI) of Antigen 1 Antibody Titers
Time Frame: From Day 1 (baseline) to Day 29
GMI is defined as the geometric mean of the ratios of the post dosing titer over the Day 1 titer. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 2 YA: GMI of Antigen 1 Antibody Titers
Time Frame: From Day 1 (baseline) to Day 29
GMI is defined as the geometric mean of the ratios of the post dosing titer over the Day 1 titer. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 1 OA: GMI of Antigen 1 Antibody Titers
Time Frame: From Day 1 (baseline) to Day 29
GMI is defined as the geometric mean of the ratios of the post dosing titer over the Day 1 titer. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 2 OA: GMI of Antigen 1 Antibody Titers
Time Frame: From Day 1 (baseline) to Day 29
GMI is defined as the geometric mean of the ratios of the post dosing titer over the Day 1 titer. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 1 YA: Percentage of Participants With Antigen 1 Antibody Seroconversion Rate (SCR)
Time Frame: From Day 1 (baseline) to Day 29
SCR is defined as the percentage of dosed participants who have either an anti-vaccine antibody pre-dose titer \< 1:10 and a post-dose anti-vaccine antibody titer \>= 1:40 or a pre-dose anti-vaccine antibody titer \>= 1:10 and at least a 4-fold increase in post-dose anti-vaccine antibody titer. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 2 YA: Percentage of Participants With Antigen 1 Antibody SCR
Time Frame: From Day 1 (baseline) to Day 29
SCR is defined as the percentage of dosed participants who have either an anti-vaccine antibody pre-dose titer \< 1:10 and a post-dose anti-vaccine antibody titer \>= 1:40 or a pre-dose anti-vaccine antibody titer \>= 1:10 and at least a 4-fold increase in post-dose anti-vaccine antibody titer. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 1 OA: Percentage of Participants With Antigen 1 Antibody SCR
Time Frame: From Day 1 (baseline) to Day 29
SCR is defined as the percentage of dosed participants who have either an anti-vaccine antibody pre-dose titer \< 1:10 and a post-dose anti-vaccine antibody titer \>= 1:40 or a pre-dose anti-vaccine antibody titer \>= 1:10 and at least a 4-fold increase in post-dose anti-vaccine antibody titer. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 2 OA: Percentage of Participants With Antigen 1 Antibody SCR
Time Frame: From Day 1 (baseline) to Day 29
SCR is defined as the percentage of dosed participants who have either an anti-vaccine antibody pre-dose titer \< 1:10 and a post-dose anti-vaccine antibody titer \>= 1:40 or a pre-dose anti-vaccine antibody titer \>= 1:10 and at least a 4-fold increase in post-dose anti-vaccine antibody titer. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 1 YA: Percentage of Participants With Antigen 1 Antibody Seroprotection Rate (SPR)
Time Frame: At Day 1
SPR is defined as the percentage of dosed participants with a anti-vaccine antibody titer \>= 1:40. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 2 YA: Percentage of Participants With Antigen 1 Antibody SPR
Time Frame: At Day 1
SPR is defined as the percentage of dosed participants with a anti-vaccine antibody titer \>= 1:40. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 1 OA: Percentage of Participants With Antigen 1 Antibody SPR
Time Frame: At Day 1
SPR is defined as the percentage of dosed participants with a anti-vaccine antibody titer \>= 1:40. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 2 OA: Percentage of Participants With Antigen 1 Antibody SPR
Time Frame: At Day 1
SPR is defined as the percentage of dosed participants with a anti-vaccine antibody titer \>= 1:40. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 1 YA: Percentage of Participants With Antigen 1 Antibody SPR
Time Frame: At Day 29
SPR is defined as the percentage of dosed participants with a anti-vaccine antibody titer \>= 1:40. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 2 YA: Percentage of Participants With Antigen 1 Antibody SPR
Time Frame: At Day 29
SPR is defined as the percentage of dosed participants with a anti-vaccine antibody titer \>= 1:40. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 1 OA: Percentage of Participants With Antigen 1 Antibody SPR
Time Frame: At Day 29
SPR is defined as the percentage of dosed participants with a anti-vaccine antibody titer \>= 1:40. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Part 2 OA: Percentage of Participants With Antigen 1 Antibody SPR
Time Frame: At Day 29
SPR is defined as the percentage of dosed participants with a anti-vaccine antibody titer \>= 1:40. Assay 1= with egg propagated Influenza virus and Assay 2= with cell propagated Influenza virus.
Secondary Outcomes
- Part 2 YA: Percentage of Participants With Antigen 2 Antibody SCR(From Day 1 (baseline) to Day 29)
- Part 1 OA: Percentage of Participants With Antigen 2 Antibody SCR(From Day 1 (baseline) to Day 29)
- Part 2 OA: Percentage of Participants With Antigen 2 Antibody SCR(From Day 1 (baseline) to Day 29)
- Part 1 OA: GMI of Antigen 2 Antibody Titer(From Day 1 (baseline) to Day 29)
- Part 2 OA: GMI of Antigen 2 Antibody Titer(From Day 1 (baseline) to Day 29)
- Part 1 YA: Percentage of Participants With Antigen 2 Antibody SCR(From Day 1 (baseline) to Day 29)
- Part 1 YA: GMT of Antigen 2 Antibody Titer(At Day 29)
- Part 2 YA: GMT of Antigen 2 Antibody Titer(At Day 29)
- Part 1 OA: GMT of Antigen 2 Antibody Titer(At Day 29)
- Part 2 OA: GMT of Antigen 2 Antibody Titer(At Day 29)
- Part 1 YA: GMI of Antigen 2 Antibody Titer(From Day 1 (baseline) to Day 29)
- Part 2 YA: GMI of Antigen 2 Antibody Titer(From Day 1 (baseline) to Day 29)
- Part 1 YA: Number of Participants Reporting Any Solicited Administration Site Adverse Events (AEs)(Day 1 to Day 7)
- Part 2 YA: Number of Participants Reporting Any Solicited Administration Site AEs(Day 1 to Day 7)
- Part 1 OA: Number of Participants Reporting Any Solicited Administration Site AEs(Day 1 to Day 7)
- Part 2 OA: Number of Participants Reporting Any Solicited Administration Site AEs(Day 1 to Day 7)
- Part 1 YA: Number of Participants Reporting Any Solicited Systemic AEs(Day 1 to Day 7)
- Part 2 YA: Number of Participants Reporting Any Solicited Systemic AEs(Day 1 to Day 7)
- Part 1 OA: Number of Participants Reporting Any Solicited Systemic AEs(Day 1 to Day 7)
- Part 2 OA: Number of Participants Reporting Any Solicited Systemic AEs(Day 1 to Day 7)
- Part 1 YA: Number of Participants Reporting Any Unsolicited AEs(Day 1 to Day 28)
- Part 2 YA: Number of Participants Reporting Any Unsolicited AEs(Day 1 to Day 28)
- Part 1 OA: Number of Participants Reporting Any Unsolicited AEs(Day 1 to Day 28)
- Part 2 OA: Number of Participants Reporting Any Unsolicited AEs(Day 1 to Day 28)
- Part 1 YA: Number of Participants Reporting Serious Adverse Events (SAEs)(Day 1 to Day 183)
- Part 2 YA: Number of Participants Reporting SAEs(Day 1 to Day 183)
- Part 1 OA: Number of Participants Reporting SAEs(Day 1 to Day 183)
- Part 2 OA: Number of Participants Reporting SAEs(Day 1 to Day 183)
- Part 1 YA: Number of Participants Reporting AEs of Special Interest (AESIs)(Day 1 to Day 183)
- Part 2 YA: Number of Participants Reporting AESIs(Day 1 to Day 183)
- Part 1 OA: Number of Participants Reporting AESIs(Day 1 to Day 183)
- Part 2 OA: Number of Participants Reporting AESIs(Day 1 to Day 183)
- Part 1 YA: Number of Participants Reporting Medically Attended Adverse Events (MAAEs)(Day 1 to Day 183)
- Part 2 YA: Number of Participants Reporting MAAEs(Day 1 to Day 183)
- Part 1 OA: Number of Participants Reporting MAAEs(Day 1 to Day 183)
- Part 2 OA: Number of Participants Reporting MAAEs(Day 1 to Day 183)