Safety and Immunogenicity of the Monovalent Influenza Vaccine A (H5N8) (Inactivated, Fragmented and Adjuvanted) in Adults and Older Adults

Randomized, Double-Blind, Placebo-Controlled Phase I/II Clinical Trial To Evaluate The Safety And Immunogenicity Of The Monovalent Influenza Vaccine A (H5N8) (Inactivated, Fragmented, and Adjuvanted) From Instituto Butantan, In Adults And The Older Adults

This study aims to demonstrate the safety and immunogenicity of two formulations of the monovalent influenza vaccine candidate A (H5N8) (inactivated, fragmented, and adjuvanted with IB160) from the Instituto Butantan in adults and older adults, to be developed for situations of pandemic, epidemic or outbreak of avian type A/H5 in humans, in the context of pandemic preparedness.

This is a clinical trial (randomized, double-blind, placebo-controlled Phase I/II) to evaluate the safety and immunogenicity of two formulations of the monovalent influenza vaccine candidate A (H5N8) (inactivated, fragmented, and adjuvanted with IB160) from the Instituto Butantan in adults and older adults. Safety will be assessed by the frequency (n, %) of participants with solicited (local and systemic) and unsolicited adverse events reported within 7 days post each vaccination; as well as the frequency of adverse reactions post causality evaluation. Immunogenicity will be assessed by seroprotection and seroconversion rates in the 21 days after the second dose.

Inclusion Criteria:

1. Males and non-pregnant females aged ≥ 18 years at the time of the first study vaccination.
2. Be in good health and clinically stable (defined as having no pre-existing health condition or having a pre-existing health condition that has not required a change in treatment or hospitalization for worsening of disease in the 3 months prior to the date of the first study vaccination).
3. Agree to participate in the study and provide written informed consent prior to the initiation of any study procedures.
4. Be able and willing to comply with all study procedures, including completing Participant Diaries, collecting blood samples, and being available for scheduled study visits and contacts.
5. For females of childbearing potential, have a negative pregnancy test prior to the first study vaccination.
6. For women of childbearing potential, be willing to use effective contraceptive measures during the screening visit until at least 30 days after the second study vaccination.

Exclusion Criteria:

1. Having received any vaccine (including seasonal influenza) 28 days prior to the date of the first study vaccination or having any vaccination in the period from the first vaccination to the immune response assessment visit after the last vaccination.
2. Known hypersensitivity or allergy to eggs, chicken proteins, squalene-based adjuvants, or any other component of the investigational product.
3. History of serious adverse reaction or anaphylaxis to any previous influenza vaccine (licensed or not).
4. Having received any influenza A/H5 vaccine or history of exposure to avian influenza A/H5.
5. Presence of a bleeding disorder or any condition that contraindicates intramuscular injection.
6. Having received immunoglobulin, blood, or any blood-derived product in the 3 months prior to the date of the first study vaccination or having had immunoglobulin or blood-derived product administered during the entire follow-up of the study.
7. Having received a solid organ, bone marrow, or stem cell transplant.
8. Having a history of asplenia (anatomic or functional).
9. Having any confirmed or suspected immunosuppressive or immunodeficiency condition, including a history of human immunodeficiency virus (HIV) infection.
10. Having a history of Guillain-Barré syndrome or other demyelinating disease.
11. Having a history of neurological disease, seizures, or progressive or severe neurological disorder.
12. History of malignant neoplasm or previous history of malignant neoplasm being disease-free for 5 years at the date of the first study vaccination (with the exception of basal cell carcinoma of the skin), autoimmune disease (including type 1 diabetes mellitus), liver cirrhosis and renal failure.
13. History of significant, progressive or decompensated chronic disease in the 3 months prior to the date of the first study vaccination (complicated type 2 diabetes mellitus, liver disease, kidney disease, heart disease, advanced arteriosclerotic disease or lung disease such as oxygen-dependent chronic obstructive pulmonary disease, among others).
14. Having received or using radiotherapy, chemotherapy, cytotoxic drugs, immunosuppressants or immunomodulators in the 6 months prior to the date of the first study vaccination.
15. Use of systemic corticosteroids (oral or parenteral) in the 3 months prior to the date of the first study vaccination, at an immunosuppressive dose equivalent to a dose of ≥ 20 mg of prednisone per day for ≥ 14 days or a cumulative dose of ≥ 280 mg. Topical use of corticosteroids (e.g., cream, eye drops, inhalation and intranasal sprays) is permitted, within the dosage indicated on the product label.
16. Presenting a behavioral, cognitive disorder/disorder or psychiatric illness that, in the opinion of the Investigator, may interfere with the ability to participate in the study.
17. Infection with the human immunodeficiency virus (HIV), hepatitis B or hepatitis C.
18. Abuse of alcohol or drugs in the 12 months prior to the date of the first study vaccination, that may interfere with the ability to participate in the study.
19. Body mass index (BMI) ≥ 35 kg/m2 on the date of the first study vaccination.
20. Clinically significant abnormalities in the general physical examination.
21. Major surgery or surgery with the use of general anaesthesia planned to occur in the period from the first vaccination to the visit to assess the immune response after the last vaccination.
22. Women who are pregnant, breastfeeding or planning to become pregnant during the 30 days after the last vaccination in the study.
23. Laboratory parameter values at the screening visit equal to or greater than grade 2 will be considered as a criterion for exclusion from participation in the study.
24. Presenting any clinically significant condition or situation that, in the opinion of the Investigator, represents a risk to the participant health or may interfere with the evaluation of the study objectives, the schedule of visits, participation in or completion of the study (such as planned travel or change of residence, among others).
25. Having participated in another clinical trial involving an experimental product, with less than three months between the completion of that follow-up and the planned date of the first vaccination in this study, or plans to enter a clinical study during the period of this study.
26. Institutionalized individual (people residing in long-term care, assistance or health care institutions and deprived of liberty).

aa. Being related to or part of the research centre staff or employee directly involved in the study.