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

221824

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.

2024-04-18

2024-08-21

2025-05-21

Recruiting

Early phase I

1080

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.

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2024-04-24