A PHASE 1/2, RANDOMIZED, PARTIALLY-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
Overview
- Phase
- Phase 1
- Intervention
- Flu Pandemic mRNA_Dose level 1
- Conditions
- Influenza, Human
- Sponsor
- GlaxoSmithKline
- Enrollment
- 991
- Locations
- 21
- Primary Endpoint
- Percentage of participants with solicited administration site events [Phase 1 and Phase 2 Part A]
- Status
- Completed
- Last Updated
- 2 months ago
Overview
Brief 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 in healthy adults 18 to 85 years of age.
Detailed 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 descriptively characterize the dose level of the Flu Pandemic mRNA vaccine candidate selected from Phase 2 Part A, comparing it to an influenza vaccine in a 2-dose schedule. It will also assess safety, reactogenicity, and the immune response induced by the influenza vaccine.
Investigators
Eligibility Criteria
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 (Where applicable) 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 (if applicable) 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
- •Where applicable, FDA toxicity grades will be exclusionary.
- •Planned administration of an influenza vaccine before Day 43 time point.
- •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, 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) (including polyethylene glycol, aminoglycoside antibiotics and egg products).
- •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.
Arms & Interventions
Flu mRNA_Ph1_1_YA
YA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 1 during Phase 1, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_Dose level 1
Flu mRNA_Ph1_2_YA
YA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 2 during Phase 1, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_Dose level 2
Flu mRNA_Ph1_3_YA
YA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 3 during Phase 1, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_ Dose level 3.
Flu mRNA_Ph1_4_YA
YA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 4 during Phase 1, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_ Dose level 4
Flu mRNA_Ph1_5_YA
YA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 5 during Phase 1, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_Dose level 5
Placebo_Ph1_YA
YA participants receive 2 doses of Placebo during Phase 1, at Day 1 and at Day 22.
Intervention: Placebo
Flu mRNA_Ph1_1_OA
OA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 1 during Phase 1, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_Dose level 1
Flu mRNA_Ph1_2_OA
OA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 2 during Phase 1, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_Dose level 2
Flu mRNA_Ph1_3_OA
OA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 3 during Phase 1, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_ Dose level 3.
Flu mRNA_Ph1_4_OA
OA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 4 during Phase 1, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_ Dose level 4
Flu mRNA_Ph1_5_OA
OA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 5 during Phase 1, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_Dose level 5
Placebo_Ph1_OA
OA Adult participants receive 2 doses of Placebo during Phase 1, at Day 1 and at Day 22.
Intervention: Placebo
Flu mRNA_Ph2_1_YA Part A
YA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 1 during Phase 2 Part A, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_Dose level 1
Flu mRNA_Ph2_2_YA Part A
YA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 2 during Phase 2 Part A, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_Dose level 2
Flu mRNA_Ph2_3_YA Part A
YA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 3 during Phase 2 Part A, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_ Dose level 3.
Flu mRNA_Ph2_4_YA Part A
YA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 4 during Phase 2 Part A, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_ Dose level 4
Flu mRNA_Ph2_5_YA Part A
YA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 5 during Phase 2 Part A, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_Dose level 5
Placebo_Ph2_YA Part A
YA participants receive 2 doses of Placebo during Phase 2 Part A, at Day 1 and at Day 22.
Intervention: Placebo
Flu mRNA_Ph2_1_OA Part A
OA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 1 during Phase 2 Part A, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_Dose level 1
Flu mRNA_Ph2_2_OA Part A
OA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 2 during Phase 2 Part A, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_Dose level 2
Flu mRNA_Ph2_3_OA Part A
OA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 3 during Phase 2 Part A, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_ Dose level 3.
Flu mRNA_Ph2_4_OA Part A
OA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 4 during Phase 2 Part A, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_ Dose level 4
Flu mRNA_Ph2_5_OA Part A
OA participants receive 2 doses of Flu Pandemic mRNA\_Dose level 5 during Phase 2 Part A, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_Dose level 5
Placebo_Ph2_OA Part A
OA participants receive 2 doses of Placebo during Phase 2 Part A, at Day 1 and at Day 22.
Intervention: Placebo
Flu mRNA_Ph2 Part B
Participants receive 2 dose of Flu Pandemic mRNA dose level 6 in Phase 2 Part B, at Day 1 and at Day 22.
Intervention: Flu Pandemic mRNA_Dose level 6
Influenza Virus Vaccine_Ph2 Part B
Participants receive 2 doses of influenza virus vaccine administered in Phase 2 Part B, at Day 1 and at Day 22.
Intervention: Influenza virus vaccine
Placebo_Ph2 Part B
Participants receive 2 doses of Placebo during Phase 2 Part B, at Day 1 and at Day 22.
Intervention: Placebo
Outcomes
Primary Outcomes
Percentage of participants with solicited administration site events [Phase 1 and Phase 2 Part A]
Time Frame: From Day 22 to Day 28
The assessed solicited administration site events are pain at administration site, redness at administration site, swelling at administration site and lymphadenopathy.
Percentage of participants with solicited systemic events [Phase 1 and Phase 2 Part A]
Time Frame: From Day 22 to Day 28
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.
Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B]
Time Frame: At Day 43 compared to pre-vaccination (Day 1, pre-dosing)
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.
GMT Ratio of anti-HI antibody titers [Phase 2 Part B]
Time Frame: At Day 43
Percentage of participants with unsolicited adverse events (AEs) [Phase 1 and Phase 2 Part A]
Time Frame: From Day 22 to Day 42
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.
Percentage of participants with medically attended adverse events (MAAEs) [Phase 1 and Phase 2 Part A]
Time Frame: From Day 1 to Day 203
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.
Percentage of participants with serious adverse events (SAEs) [Phase 1 and Phase 2 Part A]
Time Frame: From Day 1 to Day 203
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.
Percentage of participants with adverse events of special interest (AESIs) [Phase 1 and Phase 2 Part A]
Time Frame: From Day 1 to Day 203
Events considered as AESIs are severe hypersensitivity reactions and myocarditis/pericarditis.
Phase 1: Percentage of participants with increase in FDA toxicity grading for hematology and clinical chemistry laboratory parameters from baseline to any level of FDA toxicity grading at Day 8
Time Frame: Baseline (Day 1), Day 8
Phase 1: Percentage of participants with increase in FDA toxicity grading in hematology and clinical chemistry laboratory parameters from baseline to any level of FDA toxicity grading at Day 29
Time Frame: Baseline (Day 1), Day 29
Phase 1: Percentage of participants with increase in haematology and clinical chemistry laboratory parameters from normal values at baseline to abnormal values at Day 8
Time Frame: Baseline (Day 1), Day 8
Phase 1: Percentage of participants with increase in hematology and clinical chemistry laboratory parameters from normal values at baseline to abnormal values at Day 29
Time Frame: Baseline (Day 1), Day 29
Percentage of participants with anti- hemagglutinin inhibition (HI) titers ≥ 1:40 at Day 43 [Phase 1 and Phase 2 Part A]
Time Frame: At Day 43
Percentage of participants with solicited administration site events [Phase 2 Part B]
Time Frame: From Day 22 to Day 28
The assessed solicited administration site events are pain at administration site, redness at administration site, swelling at administration site and lymphadenopathy.
Percentage of participants with solicited systemic events [Phase 2 Part B]
Time Frame: From Day 22 to Day 28
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.
Percentage of participants with unsolicited AEs [Phase 2 Part B]
Time Frame: From Day 22 to Day 42
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.
Percentage of participants with MAAEs [Phase 2 Part B]
Time Frame: From Day 1 to Day 203
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.
Percentage of participants with SAEs [Phase 2 Part B]
Time Frame: From Day 1 to Day 203
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.
Percentage of participants with AESIs [Phase 2 Part B]
Time Frame: From Day 1 to Day 203
Events considered as AESIs are severe hypersensitivity reactions, Aminotransferase (AT) elevation and myocarditis/pericarditis.
Percentage of participants with increase in FDA toxicity grading for clinical chemistry laboratory parameters from baseline to any level of FDA toxicity grading at Day 8 [Phase 2 Part B]
Time Frame: Baseline (Day 1), Day 8
Percentage of participants with increase in FDA toxicity grading for clinical chemistry laboratory parameters from baseline to any level of FDA toxicity grading at Day 29 [Phase 2 Part B]
Time Frame: Baseline (Day 1), Day 29
Percentage of participants with increase in clinical chemistry laboratory parameters from normal values at baseline to abnormal values at Day 8 [Phase 2 Part B]
Time Frame: Baseline (Day 1), Day 8
Percentagev of participants with increase in clinical chemistry laboratory parameters from normal values at baseline to abnormal values at Day 29 [Phase 2 Part B]
Time Frame: Baseline (Day 1), Day 29
Percentage of participants with anti-HI titers ≥ 1:40 at Day 43 [Phase 2 Part B]
Time Frame: At Day 43
Percentage of participants with solicited administration site events [Phase 1 and Phase 2 Part A]
Time Frame: From Day 1 to Day 7
The assessed solicited administration site events are pain at administration site, redness at administration site, swelling at administration site and lymphadenopathy.
Percentage of participants with solicited systemic events [Phase 1 and Phase 2 Part A]
Time Frame: From Day 1 to Day 7
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.
Percentage of participants with unsolicited adverse events (AEs) [Phase 1 and Phase 2 Part A]
Time Frame: From Day 1 to Day 21
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.
Percentage of participants with solicited administration site events [Phase 2 Part B]
Time Frame: From Day 1 to Day 7
The assessed solicited administration site events are pain at administration site, redness at administration site, swelling at administration site and lymphadenopathy.
Percentage of participants with solicited systemic events [Phase 2 Part B]
Time Frame: From Day 1 to Day 7
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.
Percentage of participants with unsolicited AEs [Phase 2 Part B]
Time Frame: From Day 1 to Day 21
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.
Secondary Outcomes
- Percentage of seropositive participants for the HA antibody titers [Phase 1 and Phase 2 Part A](At Day 1, Day 22, Day 29, Day 43, and Day 203)
- GMT of Anti-HI antibody titers [Phase 2 Part B](At Day 1, Day 22, Day29, Day 43 and Day 203)
- GMI of anti-HI antibody titers [Phase 2 Part B](At Day 203 compared to pre-vaccination (Day 1, pre-dosing))
- Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B](At Day 203 compared to pre-vaccination (Day 1, pre-dosing))
- Geometric mean titers (GMTs) of HI antibody titers [Phase 1 and Phase 2 Part A](At Day 1, Day 22, Day 29, Day 43, and Day 203)
- Percentage of participants with anti-HI antibody >= 1:40 [Phase 2 Part B](At Day 1, Day 22, Day 29, Day 43 and Day 203)
- Geometric mean increase (GMI) of HI antibody titers [Phase 1 and Phase 2 Part A](At Day 22 compared to pre-vaccination (Day 1, pre-dosing))
- Geometric mean increase (GMI) of anti-HI antibody titers [Phase 1 and Phase 2 Part A](At Day 203 compared to pre-vaccination (Day 1, pre-dosing))
- Percentage of participants with HI antibody Seroconversion rate (SCR) [Phase 1 and Phase 2 Part A](At Day 22 compared to pre-vaccination (Day 1, pre-dosing))
- Percentage of participants with seropositivity of anti-HI antibody titers [Phase 2 Part B](At Day 1, Day 22, Day 29, Day 43 and Day 203)
- Seroconversion rate (SCR) of anti-HI antibody titers [Phase 1 and Phase 2 Part A](At Day 203 compared to pre-vaccination (Day 1, pre-dosing))
- Percentage of participants with anti-HI antibody titers >= 1:40 [Phase 1 and Phase 2 Part A](At Day 22, Day 29, and Day 203)
- Geometric mean increase (GMI) of anti-HI antibody titers [Phase 1 and Phase 2 Part A](At Day 29 compared to pre-vaccination (Day 1, pre-dosing))
- Geometric mean increase (GMI) of anti-HI antibody titers [Phase 1 and Phase 2 Part A](At Day 43 compared to pre-vaccination (Day 1, pre-dosing))
- Seroconversion rate (SCR) of anti-HI antibody titers [Phase 1 and Phase 2 Part A](At Day 29 compared to pre-vaccination (Day 1, pre-dosing))
- Seroconversion rate (SCR) of anti-HI antibody titers [Phase 1 and Phase 2 Part A](At Day 43 compared to pre-vaccination (Day 1, pre-dosing))
- GMI of anti-HI antibody titers [Phase 2 Part B](At Day 22 compared to pre-vaccination (Day 1, pre-dosing))
- GMI of anti-HI antibody titers [Phase 2 Part B](At Day 29 compared to pre-vaccination (Day 1, pre-dosing))
- GMI of anti-HI antibody titers [Phase 2 Part B](At Day 43 compared to pre-vaccination (Day 1, pre-dosing))
- Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B](At Day 22 compared to pre-vaccination (Day 1, pre-dosing))
- Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B](At Day 29 compared to pre-vaccination (Day 1, pre-dosing))
- Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B](At Day 43 compared to pre-vaccination (Day 1, pre-dosing))