A Study to Find and Confirm the Dose and Assess Safety, Reactogenicity and Immune Response of a Vaccine Against Pandemic H5N1 Influenza Virus in Healthy Younger and Older Adults

Influenza, Human Clinical Trial

Official title:

A Phase 1/2, Randomized, Observer-blind, Dose-finding/Dose-confirmation Study to Evaluate the Safety, Reactogenicity and Immunogenicity of the mRNA-based Investigational Pandemic H5 Influenza Vaccine Candidate Administered in Healthy Younger and Older Adults

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06382311
• Other study ID #: 221824
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 18, 2024
• Est. completion date: May 21, 2025

Study information

• Verified date: April 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to evaluate the safety, reactogenicity and immunogenicity of the Flu Pandemic messenger RNA (mRNA) vaccine (including dose-finding and dose-confirmation) administered healthy adults 18 to 85 years of age.

Description:

Phase 1 (Ph1) of the study aims to evaluate the reactogenicity, safety, and immunogenicity of 5 dose levels of the investigational vaccine, compared with a placebo, in both younger adults (YA) and older adults (OA). Participants will receive two doses, 21 days apart, with safety data collected up to Day 29. The data from this phase will support the safety evaluation of the assessed dose levels and enable further assessment in higher number of participants in Phase 2 Part A. Phase 2 (Ph2) Part A will assess the immunogenicity, reactogenicity, and safety of the same 5 dose levels evaluated in Phase 1, with the aim of identifying the doses to proceed to Phase 2 Part B. Phase 2 Part B will evaluate the reactogenicity, safety, and immunogenicity of either up to 2 dose levels selected from Phase 2 Part A (Scenario 1), or up to 2 higher dose levels (Scenario 2) in a one dose schedule manner.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1080
• Est. completion date: May 21, 2025
• Est. primary completion date: August 21, 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 64 yoa (i.e., 64 years + 364 days; YAs) or between and including 65 and 85 yoa (i.e., 85 years + 364 days; OAs) at the time of the first study intervention administration.
• Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the eDiary, return for follow-up visits).
• Body mass index (BMI) more than or equal to (=)18 kilogram per square meter (kg/m²) and less than or equal to (=) 35kg/m².
• Written informed consent obtained from the participant prior to performance of any study-specific procedure.
• Healthy participants or medically stable patients as established by medical history, clinical examination, and screening safety laboratory assessments (in Phase 1 and in Phase 2 Part B only for 10 first participants enrolled in each group in each age category [Segment 1], if Scenario 2 is evaluated). 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 change in therapy or hospitalization for worsening disease during 3 months before enrollment.
• Females of nonchildbearing potential may be enrolled in the study.
• Females of childbearing potential may be enrolled in the study, if the participant:
• has practiced adequate contraception for 1 month prior to study intervention administration, and
• has a negative pregnancy test at Screening Visit in Phase 1 and Phase 2 Part B (only 10 first participants enrolled in each group in each age category [Segment 1], if Scenario 2 is evaluated) and on the day of each study intervention administration, and
• has agreed to continue adequate contraception for at least 1 month after completion of the last dose of study intervention. Exclusion Criteria: Medical conditions
• Only in Phase 1 and Phase 2 Part B (only first 10 participants enrolled in each group in each age category [Segment 1], if Scenario 2 is evaluated): FDA toxicity Grade 1 laboratory values will be acceptable, as long as these values are not considered clinically significant by the investigator. The investigator should use his/her clinical judgment to decide which abnormalities are clinically significant. Any laboratory value meeting FDA toxicity grade 2 or above is exclusionary.
• Planned administration of an influenza vaccine before Day 43 time point in Phase 1 and Phase 2 Part A and before Day 22 timepoint in Phase 2 Part B.
• Current or past malignancy, unless completely resolved without clinically significant sequelae (e.g., no evidence of disease following successful treatment of basal cell carcinoma cases are allowed) for >5 years.
• Has any medical disease or psychiatric condition that, in the opinion of the investigator, precludes study participation because it would place the participant at an unacceptable risk of injury, would render them unable to meet the requirements of the protocol, or may interfere with successful completion of the study.
• Has a bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following intramuscular (IM) injections.
• 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 (only for 50 remaining participants in each dose level in each age category in the Segment 2 of Part B, if Scenario 2 is evaluated), 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 CD4 cell count is =200/mm³ and their viral load has been undetectable (i.e., HIV-RNA <50 copies/mL) (based on medical records, no laboratory testing required).
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s) (polyethylene glycol, and aminoglycoside antibiotics).
• History of 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.
• History of or current suspicion of myocarditis or pericarditis (including following administration, of an mRNA vaccine); or idiopathic cardiomyopathy, or presence of any medical condition that increases the risk myocarditis or pericarditis, including cocaine abuse, cardiomyopathy, endomyocardial fibrosis, hypereosinophilic syndrome, hypersensitivity myocarditis, eosinophilic granulomatosis with polyangiitis and persistent myocardial infection.
• 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
• Use of any investigational or non-registered product (drug, vaccine, or invasive medical device) other than the study intervention(s) during the period beginning 28 days before the dose of study intervention(s) (Day -28 to Day 1), or their planned use during the study period.
• Administration of a vaccine not foreseen by the study protocol in the period starting 28 days before the study intervention administration or planned administration within 21 days after the (last) study intervention administration*. *If emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) 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.
• Chronic administration of immune-modifying drugs (defined as more than 14 consecutive days in total) and/or planned use of long-acting immune-modifying treatments at any time up to the end of the study.
• Up to 3 months prior to the study intervention administration:
• For corticosteroids, this will mean prednisone equivalent
• 20 mg/day. Inhaled, intra-articular and topical corticosteroids are allowed. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 28 days before study vaccine administration.
• Up to 3 months prior to study intervention administration: long-acting immune-modifying drugs including among others immunotherapy (e.g., TNF-inhibitors), monoclonal antibodies, antitumoral medication.
• Administration of immunoglobulins and/or any blood products or plasma derivatives within 3 months before study intervention administration through end of study.

Prior/concurrent clinical study experience:

• 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).
• Participated in an A(H5) influenza vaccine study in the past or have a history of A(H5) influenza infection prior to dosing in this study. This includes influenza subtypes A(H5N1), A(H5N8), A(H5N6).

Other exclusion criteria:

• Pregnant or lactating female participant.
• Female planning to become pregnant or planning to discontinue contraceptive precautions within 1 months after completion of the vaccination series.
• Has a history of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures.
• 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.
• Planned move during the study period that will prohibit participating in the study until study end.
• Donation of blood 3 months prior to the study intervention administration and during the study period.

Related Conditions & MeSH terms

• Influenza, Human

Intervention

Biological:
• Flu Pandemic mRNA_Dose level 1
2 doses of study intervention are administered to participants intramuscularly. If selected as dose level 1 or dose level 2 in Phase 2 Part B, 1 dose is administered to participants.
• Flu Pandemic mRNA_Dose level 2
2 doses of study intervention are administered to participants intramuscularly. If selected as dose level 1 or dose level 2 in Phase 2 Part B, 1 dose is administered to participants.
• Flu Pandemic mRNA_ Dose level 3.
2 doses of study intervention are administered to participants intramuscularly. If selected as dose level 1 or dose level 2 in Phase 2 Part B, 1 dose is administered to participants.
• Flu Pandemic mRNA_ Dose level 4
2 doses of study intervention are administered to participants intramuscularly. If selected as dose level 1 or dose level 2 in Phase 2 Part B, 1 dose is administered to participants.
• Flu Pandemic mRNA_Dose level 5
2 doses of study intervention are administered to participants intramuscularly. If selected as dose level 1 or dose level 2 in Phase 2 Part B, 1 dose is administered to participants.
• Flu Pandemic mRNA_Dose level 6
1 dose of study intervention is administered to participants intramuscularly.
• Flu Pandemic mRNA_Dose level 7
1 dose of study intervention is administered to participants intramuscularly.

Drug:
• Placebo
2 doses of Placebo are administered intramuscularly to participants in Phase 1 and Phase 2 Part A and 1 dose is administered to participants in Phase 2 Part B.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Anniston	Alabama
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Chamblee	Georgia
United States	GSK Investigational Site	Edmond	Oklahoma
United States	GSK Investigational Site	El Dorado	Kansas
United States	GSK Investigational Site	Fort Collins	Colorado
United States	GSK Investigational Site	Fort Myers	Florida
United States	GSK Investigational Site	Greensboro	North Carolina
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Lenexa	Kansas
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Norfolk	Virginia
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Rochester	New York
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	West Palm Beach	Florida
United States	GSK Investigational Site	Winston-Salem	North Carolina
United States	GSK Investigational Site	Yukon	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with solicited administration site events [Phase 1 and Phase 2 Part A]	The assessed solicited administration site events are pain at administration site, redness at administration site, swelling at administration site and lymphadenopathy.	From Day 1 to Day 7
Primary	Percentage of participants with solicited administration site events [Phase 1 and Phase 2 Part A]	The assessed solicited administration site events are pain at administration site, redness at administration site, swelling at administration site and lymphadenopathy.	From Day 22 to Day 28
Primary	Percentage of participants with solicited systemic events [Phase 1 and Phase 2 Part A]	The assessed solicited systemic events are fever, headache, myalgia, arthralgia, fatigue, and chills. Fever is defined as temperature greater than or equal to (>=)38 degrees Celsius (°C)/ 100.4 Fahrenheit (°F) regardless the location of measurement.	From Day 1 to Day 7
Primary	Percentage of participants with solicited systemic events [Phase 1 and Phase 2 Part A]	The assessed solicited systemic events are fever, headache, myalgia, arthralgia, fatigue and chills. Fever is defined as temperature greater than or equal to (>=)38 degrees Celsius (°C)/ 100.4 Fahrenheit (°F) regardless the location of measurement.	From Day 22 to Day 28
Primary	Percentage of participants with unsolicited adverse events (AEs) [Phase 1 and Phase 2 Part A]	An unsolicited AE is 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 nonserious AEs.	From Day 1 to Day 21
Primary	Percentage of participants with unsolicited adverse events (AEs) [Phase 1 and Phase 2 Part A]	An unsolicited AE is 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 nonserious AEs.	From Day 22 to Day 42
Primary	Percentage of participants with medically attended adverse events (MAAEs) [Phase 1 and Phase 2 Part A]	An MAAE is defined as an unsolicited AE for which the participant receives medical attention such as hospitalization, or an emergency room visit, or visit to/by a health care provider.	From Day 1 to Day 203
Primary	Percentage of participants with serious adverse events (SAEs) [Phase 1 and Phase 2 Part A]	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, abnormal pregnancy outcomes, is a suspected transmission of any infectious agent via an authorized medicinal product.	From Day 1 to Day 203
Primary	Percentage of participants with adverse events of special interest (AESIs) [Phase 1 and Phase 2 Part A]	Events considered as AESIs are severe hypersensitivity reactions and myocarditis/pericarditis.	From Day 1 to Day 203
Primary	Phase 1: Percentage of participants with increased in FDA toxicity grading for hematology and clinical chemistry laboratory parameters from baseline to any level of FDA toxicity grading at Day 8		Baseline (Day 1), Day 8
Primary	Phase 1: Percentage of participants with increased in FDA toxicity grading in hematology and clinical chemistry laboratory parameters from baseline to any level of FDA toxicity grading at Day 29		Baseline (Day 1), Day 29
Primary	Phase 1: Percentage of participants with increased in haematology and clinical chemistry laboratory parameters from normal values at baseline to abnormal values at Day 8		Baseline (Day 1), Day 8
Primary	Phase 1: Percentage of participants with increased in hematology and clinical chemistry laboratory parameters from normal values at baseline to abnormal values at Day 29		Baseline (Day 1), Day 29
Primary	Percentage of participants with anti- hemagglutinin inhibition (HI) titers >= 1:40 at Day 43 [Phase 1 and Phase 2 Part A]		At Day 43
Primary	Percentage of participants with solicited administration site events [Phase 2 Part B]	The assessed solicited administration site events are pain at administration site, redness at administration site, swelling at administration site and lymphadenopathy.	From Day 1 to Day 7
Primary	Percentage of participants with solicited systemic events [Phase 2 Part B]	The assessed solicited systemic events are fever, headache, myalgia, arthralgia, fatigue, and chills. Fever is defined as temperature >= 38°C/100.4°F regardless the location of measurement. The preferred location for measuring temperature is axillary.	From Day 1 to Day 7
Primary	Percentage of participants with unsolicited AEs [Phase 2 Part B]	An unsolicited AE is 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 nonserious AEs.	From Day 1 to Day 21
Primary	Percentage of participants with MAAEs [Phase 2 Part B]	MAAE is defined as an unsolicited AE for which the participant receives medical attention such as hospitalization, or an emergency room visit, or visit to/by a health care provider.	From Day 1 to Day 183
Primary	Percentage of participants with SAEs [Phase 2 Part B]	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, abnormal pregnancy outcomes, is a suspected transmission of any infectious agent via an authorized medicinal product.	From Day 1 to Day 183
Primary	Percentage of participants with AESIs [Phase 2 Part B]	Events considered as AESIs are severe hypersensitivity reactions and myocarditis/pericarditis.	From Day 1 to Day 183
Primary	Percentage of participants with increased in FDA toxicity grading for hematology and clinical chemistry laboratory parameters from baseline to any level of FDA toxicity grading at Day 8 [Phase 2 Part B]		Baseline (Day 1), Day 8
Primary	Percentage of participants with increased in hematology and clinical chemistry laboratory parameters from normal values at baseline to abnormal values at Day 8 [Phase 2 Part B]		Baseline (Day 1), Day 8
Primary	Percentage of participants with anti-HI titers >= 1:40 at Day 22 [Phase 2 Part B]		At Day 22
Secondary	Geometric mean titers (GMTs) of HA antibody titers [Phase 1 and Phase 2 Part A]		At Day 1, Day 22, Day 29, Day 43, and Day 203
Secondary	Geometric mean increase (GMI) of HA antibody titers [Phase 1 and Phase 2 Part A]	GMI is defined as the geometric mean of the ratios of the post-vaccination to the pre-vaccination titer.	At Day 22 compared to pre-vaccination (Day 1, pre-dosing)
Secondary	Geometric mean increase (GMI) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]	GMI is defined as the geometric mean of the within participant ratios of the post-vaccination anti-HI antibody titer to the pre-vaccination anti-HI antibody titer.	At Day 29 compared to pre-vaccination (Day 1, pre-dosing)
Secondary	Geometric mean increase (GMI) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]	GMI is defined as the geometric mean of the within participant ratios of the post-vaccination anti-HI antibody titer to the pre-vaccination anti-HI antibody titer.	At Day 43 compared to pre-vaccination (Day 1, pre-dosing)
Secondary	Geometric mean increase (GMI) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]	GMI is defined as the geometric mean of the within participant ratios of the post-vaccination anti-HI antibody titer to the pre-vaccination anti-HI antibody titer.	At Day 203 compared to pre-vaccination (Day 1, pre-dosing)
Secondary	Percentage of participants with HA antibody Seroconversion rate (SCR) [Phase 1 and Phase 2 Part A]	HI seroconversion is defined as a post-dose titer >= 1:40 in the serum of participants with pre-dose titer below 1:10 or as a >= 4-fold rise in post dose HI titers with pre- dose titer >= 1:10.	At Day 22 compared to pre-vaccination (Day 1, pre-dosing)
Secondary	Seroconversion rate (SCR) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]	HI seroconversion is defined as a post-dose titer >= 1:40 in the serum of participants with pre-dose titer below 1:10 or as a >= 4-fold rise in post dose HI titers with pre- dose titer >= 1:10.	At Day 29 compared to pre-vaccination (Day 1, pre-dosing)
Secondary	Seroconversion rate (SCR) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]	HI seroconversion is defined as a post-dose titer >= 1:40 in the serum of participants with pre-dose titer below 1:10 or as a >= 4-fold rise in post dose HI titers with pre- dose titer >= 1:10.	At Day 43 compared to pre-vaccination (Day 1, pre-dosing)
Secondary	Seroconversion rate (SCR) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]	HI seroconversion is defined as a post-dose titer >= 1:40 in the serum of participants with pre-dose titer below 1:10 or as a >= 4-fold rise in post dose HI titers with pre- dose titer >= 1:10.	At Day 203 compared to pre-vaccination (Day 1, pre-dosing)
Secondary	Percentage of participants with anti-HI antibody titers >= 1:40 [Phase 1 and Phase 2 Part A]		At Day 22, Day 29, Day 43, and Day 203
Secondary	Percentage of seropositive participants for the HA antibody titers [Phase 1 and Phase 2 Part A]	Seropositivity is defined as titers >= lower limit of quantification (LLOQ) at the defined timepoints.	At Day 1, Day 22, Day 29, Day 43, and Day 203
Secondary	GMT of Anti-HI antibody titers [Phase 2 Part B]		At Day 1, Day 8, Day 22, and Day 183
Secondary	GMI of anti-HI antibody titers [Phase 2 Part B]	GMI is defined as the geometric mean of the within participant ratios of the post-vaccination anti-HI antibody titer to the pre-vaccination anti-HI antibody titer.	At Day 8 compared to pre-vaccination (Day 1, pre-dosing)
Secondary	GMI of anti-HI antibody titers [Phase 2 Part B]	GMI is defined as the geometric mean of the within participant ratios of the post-vaccination anti-HI antibody titer to the pre-vaccination anti-HI antibody titer.	At Day 22 compared to pre-vaccination (Day 1, pre-dosing)
Secondary	GMI of anti-HI antibody titers [Phase 2 Part B]	GMI is defined as the geometric mean of the within participant ratios of the post-vaccination anti-HI antibody titer to the pre-vaccination anti-HI antibody titer.	At Day 183 compared to pre-vaccination (Day 1, pre-dosing)
Secondary	Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B]	HI seroconversion is defined as a post-dose titer >=1:40 in the serum of participants with pre-dose titer below 1:10 or as a >= 4-fold rise in post dose HI titers with pre- dose titer >=1:10.	At Day 8 compared to pre-vaccination (Day 1, pre-dosing)
Secondary	Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B]	HI seroconversion is defined as a post-dose titer >=1:40 in the serum of participants with pre-dose titer below 1:10 or as a >=4-fold rise in post dose HI titers with pre- dose titer >=1:10.	At Day 22 compared to pre-vaccination (Day 1, pre-dosing)
Secondary	Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B]	HI seroconversion is defined as a post-dose titer >=1:40 in the serum of participants with pre-dose titer below 1:10 or as a >=4-fold rise in post dose HI titers with pre- dose titer >=1:10.	At Day 183 compared to pre-vaccination (Day 1, pre-dosing)
Secondary	Percentage of participants with anti-HI antibody >= 1:40 [Phase 2 Part B]		At Day 8, Day 22, and Day 183
Secondary	Percentage of participants with seropositivity of anti-HI antibody titers [Phase 2 Part B]	Seropositivity is defined as titers >= LLOQ at the defined timepoints.	At Day 1, Day 8, Day 22, and Day 183