A Study to Assess the Safety and Immune Response of a Vaccine Against Influenza in Healthy Younger and Older Adults

Influenza, Human Clinical Trial

Official title:

A Phase 1/2, Randomized, Dose-finding/Dose-confirmation Study to Evaluate the Reactogenicity, Safety and Immunogenicity of mRNA-based Multivalent Seasonal Influenza Vaccine Candidates Administered in Healthy Younger and Older Adults

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05823974
• Other study ID #: 217884
• Secondary ID: 2022-502308-66-0
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: February 27, 2023
• Est. completion date: August 12, 2024

Study information

• Verified date: February 2024
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find and confirm the dose and asses the reactogenicity, safety and immune response of GlaxoSmithKline's (GSK) messenger RNA (mRNA)-based multivalent seasonal influenza vaccine (GSK4382276A) candidates administered in healthy younger and older adults (OA).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1256
• Est. completion date: August 12, 2024
• Est. primary completion date: July 11, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• A male or female between and including 18 and 50 years of age in Phase 1 and between and including 18 and 85 years of age (YA: 18-64; OA: 65-85) in Phase 2 at the time of the study intervention administration.

• Healthy participants or medically stable participants as established by medical history, clinical examination, and safety laboratory assessments. Participants with chronic medical conditions with or without specific treatment 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 enrollment.

• Body mass index (BMI) >=18 kilograms per meter square (kg/m^2) and less than or equal to (<=) 35 kg/m^2.

• 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

• Only in Phase 1: Any clinically significant* hematological, biochemical, urinalysis or (hemoglobin A1c) HbA1c laboratory abnormality.

*The investigator should use the clinical judgment to decide which abnormalities are clinically significant.

• Participant tested positive for influenza by local health authority-approved testing methods within 180 days prior to Day 1.

• Current or past malignancy, unless completely resolved without clinically significant 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). However, in Phase 2, HIV-infected individuals may be enrolled if participants 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 (mm^3) and their viral load has been undetectable (i.e., HIV-RNA less than (<) 50 copies/milliliter [mL]) (based on medical records, no laboratory testing required).

• History of myocarditis or pericarditis less than or equal to 10 years prior to vaccine administration, including a history of myocarditis or pericarditis following vaccination with an mRNA coronavirus disease 2019 (COVID-19) vaccine.

• Participants with history of hypersensitivity or severe allergic reaction to any previous vaccine or hypersensitivity likely to be exacerbated by any component of the study intervention (including latex, polyethylene glycol, egg protein and aminoglycoside antibiotics).

• History of, 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 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.

Prior/Concomitant therapy

• Administration of an influenza vaccine (including any of the study investigational vaccines) within 180 days before enrollment or planned administration within 28 days (Day 29) after the study intervention administration.

• Phase 1: Administration of a vaccine not foreseen by the study protocol in the period starting 28 days (Day -28) before the study intervention administration or planned administration within 28 days (Day 29) after the study intervention administration. Phase 2: Administration of a vaccine not foreseen by the study protocol in the period starting 15 days (Day -15) before the study intervention administration or planned administration within 28 days (Day 29) after the study intervention administration.

*In case emergency mass vaccination for an unforeseen public health threat is recommended and/or organized by public health authorities outside the routine immunization program, the time period described above can be reduced to 7 days if, necessary for that vaccine, provided it is used according to the local governmental recommendations and that the Sponsor is notified accordingly.

• Use of any investigational or non-registered product (drug, vaccine, or invasive medical device) other than the study intervention during the period beginning 30 days before the study intervention administration, or their planned use during the study period.

• Administration of long-acting immune-modifying drugs within 90 days before enrollment or planned use at any time during the study period.

• Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the study intervention administration, or planned administration during the study period. Administration of monoclonal antibodies specifically directed against the spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), for treatment of COVID-19 disease is allowed.

• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the study intervention administration. For corticosteroids, this will mean prednisone equivalent >=20 milligrams (mg)/day. Inhaled, topical and intraarticular steroids are allowed.

Other exclusions

• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (drug/invasive medical device).

• Pregnant or lactating female.

• Bedridden participants.

• Female planning to become pregnant or planning to discontinue contraceptive precautions within the 1-month post-dosing period.

• Alcoholism or substance use disorder within the past 24 months based on the presence of 2 or more of the following abuse criteria: hazardous use, social/interpersonal problems related to use, neglect of major roles to use, withdrawal, tolerance, use of larger amounts or longer, repeated attempts to quit or control use, much time spent using, physical or psychological problems related to use, activities given up to use, craving.

• Any study personnel or their immediate dependents, family, or household members.

• Participants with extensive tattoos covering deltoid region on both arms that would preclude the assessment of local reactogenicity.

Related Conditions & MeSH terms

• Influenza, Human

Intervention

Biological:
• Flu mRNA
Different formulations of Flu mRNA (GSK4382276A) study intervention is administered intramuscularly in the non-dominant upper deltoid to YA and OA participants in Phase 1 and Phase 2, at Day 1.

Combination Product:
• Control 1
Control 1 vaccine is administered intramuscularly in the non-dominant upper deltoid to participants in Control group from Phase 1, at Day 1 and to participants in Control YA group from Phase 2, at Day 1.
• Control 2
Control 2 vaccine is administered intramuscularly in the non-dominant upper deltoid to participants in Control OA group from Phase 2, at Day 1.

Locations

Country	Name	City	State
Belgium	GSK Investigational Site	Antwerpen
Belgium	GSK Investigational Site	Gent
Belgium	GSK Investigational Site	Ieper
Belgium	GSK Investigational Site	Kluisbergen
Belgium	GSK Investigational Site	Mechelen
Belgium	GSK Investigational Site	Tielt
Belgium	GSK Investigational Site	Wilrijk
Belgium	GSK Investigational Site	Zwalm
Canada	GSK Investigational Site	Chicoutimi	Quebec
Canada	GSK Investigational Site	Halifax	Nova Scotia
Canada	GSK Investigational Site	Quebec
Canada	GSK Investigational Site	Sherbrooke	Quebec
Canada	GSK Investigational Site	Truro
South Africa	GSK Investigational Site	Bellville
South Africa	GSK Investigational Site	East London
South Africa	GSK Investigational Site	Johannesburg	Gauteng
South Africa	GSK Investigational Site	Johannesburg	Gauteng
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Dearborn Heights	Michigan
United States	GSK Investigational Site	East Greenwich	Rhode Island
United States	GSK Investigational Site	East Syracuse	New York
United States	GSK Investigational Site	Englewood	Colorado
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Greensboro	North Carolina
United States	GSK Investigational Site	Hialeah	Florida
United States	GSK Investigational Site	Knoxville	Tennessee
United States	GSK Investigational Site	Lenexa	Kansas
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Newport News	Virginia
United States	GSK Investigational Site	Norfolk	Virginia
United States	GSK Investigational Site	Papillion	Nebraska
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Rochester	New York
United States	GSK Investigational Site	Southfield	Michigan
United States	GSK Investigational Site	Tomball	Texas
United States	GSK Investigational Site	Valparaiso	Indiana
United States	GSK Investigational Site	Wichita	Kansas
United States	GSK Investigational Site	Wilmington	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	CureVac

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants reporting each solicited administration site event	The following administration site events will be solicited: pain, redness, swelling, lymphadenopathy (defined as localized axillary, cervical or supraclavicular swelling or tenderness ipsilateral to the injection arm).	From Day 1 to Day 7
Primary	Percentage of participants reporting each solicited systemic event	The following systemic events will be solicited: fever, headache, myalgia, arthralgia, fatigue, chills. Fever is defined as temperature greater than or equal to (>=) 38 degree Celsius (°C)/100.4 degree Fahrenheit (°F) regardless the location of measurement. The route for measuring temperature can be oral, axillary or tympanic.	From Day 1 to Day 7
Primary	Percentage of participants reporting unsolicited adverse events (AEs)	An unsolicited AE is defined as an AE 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 include both serious and non-serious AEs.	From Day 1 to Day 28
Primary	Percentage of participants reporting serious adverse events (SAEs)	An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, is an abnormal pregnancy outcome, or is a suspected transmission of any infectious agent via an authorized medicinal product.	From Day 1 to Day 183
Primary	Percentage of participants reporting adverse events of special interest (AESIs)	The following events are considered as AESI in this study: severe hypersensitivity reactions within 24 hours after study intervention administration, myocarditis/pericarditis and potential immune-mediated diseases (pIMDs).	From Day 1 to Day 183
Primary	Percentage of participants reporting medically attended events (MAEs)	MAE is defined as an AE that results in an unscheduled visit to a medical professional (e.g., physician's office visits, emergency room visits or hospitalization).	From Day 1 to Day 183
Primary	Percentage of participants reporting a shift from a non-clinically significant laboratory value on Day 1 (pre-dose) to a clinically significant abnormal laboratory value on Day 8 (post-dose) and/or Day 29 (post-dose) for hematology and clinical chemistry	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.	From Day 1 (pre-dose) to Day 8 (post-dose) and/or Day 29 (post-dose)
Primary	Geometric mean titer (GMT) of antigen 1 antibody titer		At Day 29
Primary	Geometric mean increase (GMI) of antigen 1 antibody titer	GMI is defined as the geometric mean of the ratios of the post dosing titer over the Day 1 titer.	From Day 1 to Day 29
Primary	Percentage of participants with antigen 1 seroconversion rate (SCR)		From Day 1 to Day 29
Primary	Percentage of participants with antigen 1 titer >= cut off value		At Day 1 and Day 29
Primary	GMT of antigen 2 antibody titer		At Day 29
Primary	GMI of antigen 2 antibody titer	GMI is defined as the geometric mean of the ratios of the post dosing titer over the Day 1 titer.	From Day 1 to Day 29
Primary	Percentage of participants with antigen 2 SCR		From Day 1 to Day 29
Secondary	GMT of antigen 1 antibody titer		At Day 92 and Day 183
Secondary	GMI of antigen 1 antibody titer	GMI is defined as the geometric mean of the ratios of the post dosing titer over the Day 1 titer.	From Day 1 to Day 92
Secondary	GMI of antigen 1 antibody titer	GMI is defined as the geometric mean of the ratios of the post dosing titer over the Day 1 titer.	From Day 1 to Day 183
Secondary	Percentage of participants with antigen 1 titer >= cut off value		At Day 183
Secondary	GMT of antigen 2 antibody titer		At Day 92 and Day 183
Secondary	GMI of antigen 2 antibody titer	GMI is defined as the geometric mean of the ratios of the post dosing titer over the Day 1 titer.	From Day 1 to Day 92
Secondary	GMI of antigen 2 antibody titer	GMI is defined as the geometric mean of the ratios of the post dosing titer over the Day 1 titer.	From Day 1 to Day 183