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

NCT06382311
clinicaltrials.gov
Phase
Phase 1/Phase 2
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Recruitment status
Completed
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Participants
991
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Lead sponsor
GlaxoSmithKline
clinicaltrials.gov
Start date
2024-04-18
clinicaltrials.gov
Number of sites
21
clinicaltrials.gov

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.
clinicaltrials.gov
Short title
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
clinicaltrials.gov
Official title
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
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Control arm
Placebo
clinicaltrials.gov
Registry reports results
No
clinicaltrials.gov
Listing at source
Listed
clinicaltrials.gov
Recruitment status
Completed
clinicaltrials.gov
Phase
Phase 1/Phase 2
clinicaltrials.gov
Study type
Interventional
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Completion date
2026-01-13
clinicaltrials.gov
First posted
2024-04-24
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Registry last updated
2026-02-05
clinicaltrials.gov
Primary completion date
2026-01-13
clinicaltrials.gov
Start date
2024-04-18
clinicaltrials.gov

Actual participants
991
clinicaltrials.gov
Participants
991
clinicaltrials.gov
Participant count basis
Actual
clinicaltrials.gov
Protocol amendments
2
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Number of sites
21
clinicaltrials.gov

Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
GlaxoSmithKline
clinicaltrials.gov
Source registry
ClinicalTrials.gov
clinicaltrials.gov

Registry ID
NCT06382311
clinicaltrials.gov
ClinicalTrials.gov ID
NCT06382311
clinicaltrials.gov
Registry record
Open registry record
clinicaltrials.gov

Allocation
Randomised
Model
Sequential
Purpose
Prevention
Masking
Quadruple masking
Masking description
Data will be collected in an observer-blind manner in Phase 1 and Phase 2 Part A. Phase 2 Part B: 2 sub-cohorts: Observer-blind and Open label.
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. Percentage of participants with solicited administration site events [Phase 1 and Phase 2 Part A]

    Timeframe: 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.

  2. Percentage of participants with solicited administration site events [Phase 1 and Phase 2 Part A]

    Timeframe: 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.

  3. Percentage of participants with solicited systemic events [Phase 1 and Phase 2 Part A]

    Timeframe: 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.

  4. Percentage of participants with solicited systemic events [Phase 1 and Phase 2 Part A]

    Timeframe: 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.

  5. Percentage of participants with unsolicited adverse events (AEs) [Phase 1 and Phase 2 Part A]

    Timeframe: 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.

  6. Percentage of participants with unsolicited adverse events (AEs) [Phase 1 and Phase 2 Part A]

    Timeframe: 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.

  7. Percentage of participants with medically attended adverse events (MAAEs) [Phase 1 and Phase 2 Part A]

    Timeframe: 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.

  8. Percentage of participants with serious adverse events (SAEs) [Phase 1 and Phase 2 Part A]

    Timeframe: 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.

  9. Percentage of participants with adverse events of special interest (AESIs) [Phase 1 and Phase 2 Part A]

    Timeframe: From Day 1 to Day 203

    Events considered as AESIs are severe hypersensitivity reactions and myocarditis/pericarditis.

  10. 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

    Timeframe: Baseline (Day 1), Day 8

  11. 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

    Timeframe: Baseline (Day 1), Day 29

  12. 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

    Timeframe: Baseline (Day 1), Day 8

  13. 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

    Timeframe: Baseline (Day 1), Day 29

  14. Percentage of participants with anti- hemagglutinin inhibition (HI) titers ≥ 1:40 at Day 43 [Phase 1 and Phase 2 Part A]

    Timeframe: At Day 43

  15. Percentage of participants with solicited administration site events [Phase 2 Part B]

    Timeframe: 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.

  16. Percentage of participants with solicited administration site events [Phase 2 Part B]

    Timeframe: 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.

  17. Percentage of participants with solicited systemic events [Phase 2 Part B]

    Timeframe: 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.

  18. Percentage of participants with solicited systemic events [Phase 2 Part B]

    Timeframe: 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.

  19. Percentage of participants with unsolicited AEs [Phase 2 Part B]

    Timeframe: 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.

  20. Percentage of participants with unsolicited AEs [Phase 2 Part B]

    Timeframe: 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.

  21. Percentage of participants with MAAEs [Phase 2 Part B]

    Timeframe: 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.

  22. Percentage of participants with SAEs [Phase 2 Part B]

    Timeframe: 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.

  23. Percentage of participants with AESIs [Phase 2 Part B]

    Timeframe: From Day 1 to Day 203

    Events considered as AESIs are severe hypersensitivity reactions, Aminotransferase (AT) elevation and myocarditis/pericarditis.

  24. 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]

    Timeframe: Baseline (Day 1), Day 8

  25. 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]

    Timeframe: Baseline (Day 1), Day 29

And 5 more, listed on the interactive page.

  1. Geometric mean titers (GMTs) of HI antibody titers [Phase 1 and Phase 2 Part A]

    Timeframe: At Day 1, Day 22, Day 29, Day 43, and Day 203

  2. Geometric mean increase (GMI) of HI antibody titers [Phase 1 and Phase 2 Part A]

    Timeframe: At Day 22 compared to pre-vaccination (Day 1, pre-dosing)

    GMI is defined as the geometric mean of the ratios of the post-vaccination to the pre-vaccination titer.

  3. Geometric mean increase (GMI) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]

    Timeframe: At Day 29 compared to pre-vaccination (Day 1, pre-dosing)

    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.

  4. Geometric mean increase (GMI) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]

    Timeframe: At Day 43 compared to pre-vaccination (Day 1, pre-dosing)

    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.

  5. Geometric mean increase (GMI) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]

    Timeframe: At Day 203 compared to pre-vaccination (Day 1, pre-dosing)

    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.

  6. Percentage of participants with HI antibody Seroconversion rate (SCR) [Phase 1 and Phase 2 Part A]

    Timeframe: At Day 22 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.

  7. Seroconversion rate (SCR) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]

    Timeframe: At Day 29 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.

  8. Seroconversion rate (SCR) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]

    Timeframe: 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.

  9. Seroconversion rate (SCR) of anti-HI antibody titers [Phase 1 and Phase 2 Part A]

    Timeframe: At Day 203 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.

  10. Percentage of participants with anti-HI antibody titers >= 1:40 [Phase 1 and Phase 2 Part A]

    Timeframe: At Day 22, Day 29, and Day 203

  11. Percentage of seropositive participants for the HA antibody titers [Phase 1 and Phase 2 Part A]

    Timeframe: At Day 1, Day 22, Day 29, Day 43, and Day 203

    Seropositivity is defined as titers ≥ lower limit of quantification (LLOQ) at the defined timepoints.

  12. GMT of Anti-HI antibody titers [Phase 2 Part B]

    Timeframe: At Day 1, Day 22, Day29, Day 43 and Day 203

  13. GMI of anti-HI antibody titers [Phase 2 Part B]

    Timeframe: At Day 22 compared to pre-vaccination (Day 1, pre-dosing)

    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.

  14. GMI of anti-HI antibody titers [Phase 2 Part B]

    Timeframe: At Day 29 compared to pre-vaccination (Day 1, pre-dosing)

    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.

  15. GMI of anti-HI antibody titers [Phase 2 Part B]

    Timeframe: At Day 43 compared to pre-vaccination (Day 1, pre-dosing)

    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.

  16. GMI of anti-HI antibody titers [Phase 2 Part B]

    Timeframe: At Day 203 compared to pre-vaccination (Day 1, pre-dosing)

    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.

  17. Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B]

    Timeframe: At Day 22 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.

  18. Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B]

    Timeframe: At Day 29 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.

  19. Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B]

    Timeframe: 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.

  20. Seroconversion rate (SCR) of anti-HI antibody titers [Phase 2 Part B]

    Timeframe: At Day 203 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.

  21. Percentage of participants with anti-HI antibody >= 1:40 [Phase 2 Part B]

    Timeframe: At Day 1, Day 22, Day 29, Day 43 and Day 203

  22. Percentage of participants with seropositivity of anti-HI antibody titers [Phase 2 Part B]

    Timeframe: At Day 1, Day 22, Day 29, Day 43 and Day 203

    Seropositivity is defined as titers ≥ LLOQ at the defined timepoints.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
85 Years
Healthy volunteers
Yes

  • 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.

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.
  • 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.
Sources for eligibility
clinicaltrials.gov

  • GSK Investigational SiteAnniston, United States
  • GSK Investigational SiteLittle Rock, United States
  • GSK Investigational SiteFort Collins, United States
  • GSK Investigational SiteFort Myers, United States
  • GSK Investigational SiteWest Palm Beach, United States
  • GSK Investigational SiteChamblee, United States
  • GSK Investigational SiteEl Dorado, United States
  • GSK Investigational SiteLenexa, United States
  • GSK Investigational SiteLexington, United States
  • GSK Investigational SiteKansas City, United States
  • GSK Investigational SiteOmaha, United States
  • GSK Investigational SiteLas Vegas, United States
  • GSK Investigational SiteRochester, United States
  • GSK Investigational SiteGreensboro, United States
  • GSK Investigational SiteWinston-Salem, United States
  • GSK Investigational SiteEdmond, United States
  • GSK Investigational SiteYukon, United States
  • GSK Investigational SitePhiladelphia, United States
  • GSK Investigational SiteAustin, United States
  • GSK Investigational SiteNorfolk, United States
  • GSK Investigational SiteSeattle, United States
Sources for sites
clinicaltrials.gov

Related records

Drugs (3)

Lead sponsors (1)

Conditions (1)

Targets (1)