Safety and immune response of an adjuvanted H5N8 monovalent influenza vaccine 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 test tries two doses (7.5 mcg and 15 mcg) of an H5N8 monovalent flu vaccine with an adjuvant versus placebo in adults and older adults to see if it's safe and triggers protective antibodies.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 700 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Butantan Institute (Government)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 5 sites (Belo Horizonte, Minas Gerais and 4 other locations)
• Trial ID: NCT06842173 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, placebo-controlled Phase 1/2 trial enrolls adults and older adults to receive two doses of one of two formulations of an inactivated, fragmented H5N8 monovalent vaccine adjuvanted with IB160 or placebo. Safety is monitored by recording solicited local and systemic adverse events and unsolicited events within seven days after each vaccination and by evaluating adverse reactions after causality assessment. Immunogenicity is measured by seroprotection and seroconversion rates assessed 21 days after the second dose. The vaccine candidate is developed by Instituto Butantan as a preparedness measure for potential avian A/H5 outbreaks in humans.

Who should consider this trial

Good fit: Adults aged 18 years and older who are in good health or clinically stable, non-pregnant, able to comply with study procedures, and willing to provide informed consent and use contraception if of childbearing potential are ideal candidates.

Not a fit: People under 18 years, pregnant women, and those with recent unstable medical conditions that required treatment changes or hospitalization are not eligible and may not receive benefit from this trial.

Why it matters

Potential benefit: If successful, the vaccine could provide a safe, immunogenic option against H5N8 avian influenza to help with pandemic preparedness.

How similar studies have performed: Previous trials of adjuvanted inactivated H5 influenza vaccines have shown promising immunogenicity in adults, so this approach has precedent though specific H5N8 data are more limited.

Eligibility criteria

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.

Where this trial is running

Belo Horizonte, Minas Gerais and 4 other locations

• Centro de Terapias Avançadas E Inovadoras - Ct Terapias/Ufmg — Belo Horizonte, Minas Gerais, Brazil (Not_yet_recruiting)
• Plátano Centro de Pesquisa Clínica LTDA — Recife, Pernambuco, Brazil (Recruiting)
• Fundação Faculdade Regional de Medicina de São Jose do Rio Preto - (Centro integrado de Pesquisa CIP) — São José do Rio Preto, São Paulo, Brazil (Not_yet_recruiting)
• Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preta da Universidade de São Paulo - (Centro de Pesquisa Clínica - S) — Serrana, São Paulo, Brazil (Not_yet_recruiting)
• Centro de Pesquisas Clínicas do Hospital das Clínicas da FMUSP — São Paulo, Brazil (Not_yet_recruiting)

Conditions Avian Influenza A Virus; Influenza A Virus Subtype H5N8; Avian Influenza; Safety; Immunogenicity