A Phase 1 Randomized, Dose Escalation Study to Evaluate the Safety, Reactogenicity and Immunogenicity of an mRNA-based Monovalent Influenza Vaccine Candidate in Healthy Younger and Older Adults
Overview
- Phase
- Phase 1
- Intervention
- GSK4382276A Dose level 1
- Conditions
- Influenza, Human
- Sponsor
- GlaxoSmithKline
- Enrollment
- 324
- Locations
- 7
- Primary Endpoint
- Number of Participants Reporting Any Solicited Administration Site Events
- Status
- Completed
- Last Updated
- last month
Overview
Brief Summary
The purpose of this first-time-in-human (FTiH) study is to assess the safety, reactogenicity and immunogenicity of GlaxoSmithKline's (GSK) messenger RNA (mRNA)-based monovalent vaccine (GSK4382276A) candidate against influenza in healthy younger adults (YA) and older adults (OA).
Investigators
Eligibility Criteria
Inclusion Criteria
- •A male or female between and including 18 and 45 years of age (YAs) or between and including 60 and 80 years of age (OAs) at the time of the study intervention administration. The age of sentinel participants in OA category will be limited to maximum 70 years.
- •Healthy or medically stable participants as established by medical history, safety laboratory assessments and clinical examination.
- •Body mass index \>= 18 kg/m\^2 and \<= 32 kg/m\^
- •Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
- •Written informed consent obtained from the participant prior to performing any study-specific procedure.
- •Female participants of non-childbearing potential may be enrolled in the study.
- •Female participants of childbearing potential may be enrolled in the study if the participant:
- •has practiced adequate contraception for 28 days prior to study intervention administration, and
- •has a negative pregnancy test on the day of study intervention administration, and
- •has agreed to continue adequate contraception for at least 1 month after study intervention administration.
Exclusion Criteria
- •Medical conditions
- •Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or review of the participant's medical record.
- •Any clinically significant hematological coagulation or urine analysis laboratory abnormality.
- •\* The investigator should use his/her clinical judgement to decide which abnormalities are clinically significant.
- •Current or past malignancy, unless completely resolved without sequelae for \>5 years.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection, based on medical history and physical examination (no laboratory testing required).
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention (including latex, poly-ethylene-glycol, egg protein and aminoglycoside antibiotics).
- •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 medical 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 study.
Arms & Interventions
Flu mRNA_Dose level 1_Younger adults (YA)
On Day 1, YA adult participants received Flu mRNA at Dose Level 1, the lowest concentration evaluated in the study.
Intervention: GSK4382276A Dose level 1
Flu mRNA_Dose level 2 _YA
On Day 1, YA participants received Flu mRNA at Dose Level 2, which corresponds to a higher concentration than Dose Level 1.
Intervention: GSK4382276A Dose level 2
Flu mRNA_Dose level 3_YA
On Day 1, YA participants received Flu mRNA at Dose Level 3, which corresponds to a higher concentration than Dose Level 2.
Intervention: GSK4382276A Dose level 3
Flu mRNA_Dose level 4_YA
On Day 1, YA participants received Flu mRNA at Dose Level 4, which corresponds to a higher concentration than Dose Level 3.
Intervention: GSK4382276A Dose level 4
Flu mRNA_Dose level 5_YA
On Day 1, YA participants received Flu mRNA at Dose Level 5, which corresponds to a higher concentration than Dose Level 4.
Intervention: GSK4382276A Dose level 5
Flu mRNA_Dose level 6_YA
On Day 1, YA participants received Flu mRNA at Dose Level 6, which corresponds to a higher concentration than Dose Level 5.
Intervention: GSK4382276A Dose level 6
Flu mRNA_Dose level 7_YA
On Day 1, YA participants received Flu mRNA at Dose Level 7, which corresponds to a higher concentration than Dose Level 6.
Intervention: GSK4382276A Dose level 7
Flu mRNA_ Dose level 8_YA
On Day 1, YA participants received Flu mRNA at Dose Level 8, which corresponds to a higher concentration than Dose Level 7.
Intervention: GSK4382276A Dose level 8
Flu mRNA_Dose level 9_YA
On Day 1, YA participants received Flu mRNA at Dose Level 9, which corresponds to a higher concentration than Dose Level 8.
Intervention: GSK4382276A Dose level 9
Flu mRNA_Dose level 10_YA
On Day 1, YA participants received Flu mRNA at Dose Level 10, the highest concentration evaluated in the study.
Intervention: GSK4382276A Dose level 10
Pooled Control_YA
On Day 1, YA participants received a single dose of FDQ21A - NH or FDQ22A -NH administered as a control and were analyzed together as pooled group throughout the study.
Intervention: FDQ21A-NH
Pooled Control_YA
On Day 1, YA participants received a single dose of FDQ21A - NH or FDQ22A -NH administered as a control and were analyzed together as pooled group throughout the study.
Intervention: FDQ22A-NH
Flu mRNA_Dose level 7_Older adults (OA)
On Day 1, OA participants received Flu mRNA at Dose Level 7.
Intervention: GSK4382276A Dose level 7
Control_OA
On Day 1, OA participants received a single dose of FDQ21A-NH administered at as a control.
Intervention: FDQ21A-NH
Outcomes
Primary Outcomes
Number of Participants Reporting Any Solicited Administration Site Events
Time Frame: Day 1 to Day 7
Assessed solicited administration site events included pain, erythema/redness, swelling and Lymphadenopathy (defined as localized axillary, cervical or supraclavicular swelling or tenderness ipsilateral to the injection arm). Any = occurrence of the event regardless of intensity grade.
Number of Participants Reporting Any Solicited Systemic Events
Time Frame: Day 1 to Day 7
Assessed solicited systemic events included fever, chills, headache, myalgia, arthralgia and fatigue. Any = occurrence of the symptom regardless of intensity grade.
Number of Participants Reporting Any Unsolicited Adverse Events (AEs)
Time Frame: Day 1 to Day 28
An unsolicited AEs is an AEs that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow up for solicited events. Unsolicited AEs must have been communicated by a participant who has signed the informed consent or through his/her caregiver. Unsolicited AEs include both serious and non-serious AEs. Any = occurrence of the symptom regardless of intensity grade or relation to study vaccination.
Number of Participants Reporting Serious Adverse Events (SAEs)
Time Frame: Day 1 to Day 183
An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, or resulted in abnormal pregnancy outcomes, or in other situations that were considered serious per medical or scientific judgment.
Number of Participants Reporting AEs of Special Interest (AESIs)
Time Frame: Day 1 to Day 183
The following events were considered as AESI in this study: severe hypersensitivity reactions within 24 hours after study intervention administration, myocarditis/pericarditis and potential immune-mediated diseases (pIMDs).
Number of Participants Reporting Shift From Abnormal Non-clinically Significant and Normal or Missing Laboratory Value on Day 1 to Clinically Significant Abnormal Laboratory Value on Day 8 for Hematology, Clinical Chemistry, Coagulation and Urine Analysis
Time Frame: At Day 8 compared to baseline (Day 1)
Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participants condition. Normal or missing values refer to laboratory values that were within normal range or missing at baseline.
Number of Participants Reporting Shift From Abnormal Non-clinically Significant and Normal or Missing Laboratory Value on Day 1 to Clinically Significant Abnormal Laboratory Value on Day 29 for Hematology,Clinical Chemistry, Coagulation and Urine Analysis
Time Frame: At Day 29 compared to baseline (Day 1)
Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participants condition. Normal or missing values refer to laboratory values that were within normal range or missing at baseline.
Geometric Mean Titers (GMT) of Anti-vaccine Antibody Titers
Time Frame: At Day 1
GMT of Anti-vaccine Antibody Titers
Time Frame: At Day 22
Geometric Mean Increase (GMI) of Anti-vaccine Antibody Titers From Day 1 (Baseline) to Day 22
Time Frame: From Day 1 to Day 22
GMI is defined as the geometric mean of the ratios of the post-dose anti-vaccine antibody titers over the Day 1 anti-vaccine antibody titers.
Percentage of Participants With Anti-vaccine Antibody Seroconversion Rate (SCR)
Time Frame: From Day 1 to Day 22
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.
Percentage of Participants With Anti-vaccine Antibody Seroprotection Rate (SPR)
Time Frame: At Day 22
SPR is defined as the percentage of dosed participants with a anti-vaccine antibody titer ≥ 1:40.
Secondary Outcomes
- GMT of Anti-vaccine Antibody Titers(At Day 62 and Day 183)
- GMI of Anti-vaccine Antibody Titers From Day 1 (Baseline) to Day 62(From Day 1 to Day 62)
- GMI of Anti-vaccine Antibody Titers From Day 1 (Baseline) to Day 183(From Day 1 to Day 183)
- Percentage of Participants With Anti-vaccine Antibody SPR(At Day 62 and Day 183)