Influenza A
Conditions
Keywords
Avian Influenza A, mRNA Vaccine, Pandemic Influenza, VLP, H5N1, H7N9, AstraZeneca
Brief summary
The purpose of this study is to evaluate the safety and immunogenicity of two investigational vaccines, AZD4117 and AZD5315 to protect against certain strains of avian Influenza A (H5N1 and H7N9 subtypes).
Interventions
BIOLOGICALAZD4117
Intramuscular (IM) injection
BIOLOGICALAZD5315
IM injection
OTHERPlacebo
IM injection
Sponsors
AstraZeneca
Biomedical Advanced Research and Development Authority
Joint Program Executive Office (JPEO) Chemical, Biological, Radiological, and Nuclear Defense (CBRND) Enabling Biotechnologies (EB)
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Masking will be secured to the syringe after preparation by unblinded personnel
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Adults, ≥ 18 years of age at the time of signing the informed consent * Participants who are medically stable such that, according to the judgement of the Investigator, hospitalization within the study period is not anticipated and the participant appears likely to be able to remain on study through the end of protocol-specified follow-up. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months prior to enrollment * Written informed consent and any locally required authorization (eg, HIPAA in the US) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations Key
Exclusion criteria
* History of hypersensitivity to any component of the IMP * History of hypersensitivity to penicillin and its derivatives * History of severe adverse reaction and/or severe allergic reaction (eg, anaphylaxis associated with a vaccine * Known or suspected congenital or acquired immunodeficiency * Abnormal findings on screening laboratory tests * Previous history of myocarditis, pericarditis, Guillain-Barré syndrome or any other demyelinating condition * Known or suspected autoimmune conditions as determined by history and/or physical examination * Receipt of any other type of seasonal influenza vaccination from 14 days before the first dose until 28 days after the administration of the last dose of IMP * Receipt of an mRNA vaccine within 28 days before administration of IMP * Receipt or expected receipt of any other type of licensed or investigational vaccine within 28 days prior to Visit 1 (D1) or Visit 5 (D58) * Receipt of immunoglobulin or blood products within 6 months prior to administration of study intervention or expected receipt during the study * Receipt of immune-modifying drugs or immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy within 6 months prior to enrollment (or expected receipt during study), or long-term systemic corticosteroid therapy (prednisolone or equivalent at a dose of ≥ 20 mg daily for more than 2 consecutive weeks) within 6 months prior to enrollment or expected receipt during study. Topical/inhaled steroids or short-term oral steroids are permitted * Participation in another trial, or receiving interventional Study IMP, in the preceding 90 days or expected receipt of another study intervention (or participation in another trial) during the period of study follow-up * Acute (time-limited) or febrile (temperature ≥ 38.0 °C \[100.4 °F\]) illness/infection within 3 days of intended IMP administration * Individuals who have had a previous confirmed or suspected illness from influenza caused by an H5N1 or H7N9 virus * Individuals who had household contact with and/or intimate exposure to an individual with laboratory confirmed H5N1 infection, exposure to infected household poultry/ wild birds/cattle or contaminated environments with sick and dead poultry or wild birds or cattle, within 60 days prior to enrollment * Female participants who are pregnant, lactating, or of childbearing potential and not using a highly effective method of contraception or abstinence from at least 4 weeks prior to IMP administration and until at least 6 months after IMP administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with immediate unsolicited adverse events (AE) | Within 30 minutes after dosing | — |
| Percentage of participants with injection site and systemic solicited adverse reactions (AR) | Through 7 days after dosing | — |
| Percentage of participants with unsolicited AE | Through 28 days after the last dose | — |
| Percentage of participants with serious adverse events (SAE) | Through 12 months after the last dose | — |
| Percentage of participants with medically attended adverse events (MAAE) | Through 12 months after the last dose | — |
| Percentage of participants with adverse events of special interest (AESI) | Through 12 months after the last dose | — |
| Proportion of participants achieving ≥ 1:40 HAI titer post-IMP administration | Day 58 | A binary endpoint, defined as ≥ 1:40 HAI titer post-IMP administration. |
| Proportion of participants achieving seroconversion post-IMP administration | Day 58 | Seroconversion status, defined as either a pre-IMP administration HAI titer \< 1:10 and a post-IMP administration HAI titer ≥ 1:40, or a pre-IMP administration titer ≥ 1:10 and 4-fold increase in post-IMP administration titer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric mean titer (GMT) of HAI antibody | Days 1 to 389 | — |
| Geometric mean fold-rise (GMFR) of HAI antibody titers from baseline | Days 29 to 389 | The fold rise is calculated as the ratio of the post-dose titer to the pre-dose titer. |
| Proportion of participants achieving a ≥1:40 HAI titer post-IMP administration | Days 29 to 389 | A binary endpoint, defined as ≥ 1:40 HAI titer post-IMP administration. |
| Proportion of participants achieving seroconversion post-IMP administration | Days 29 to 389 | Seroconversion status, defined as either a pre-IMP administration HAI titer \< 1:10 and a post-IMP administration HAI titer ≥ 1:40, or a pre-IMP administration titer ≥ 1:10 and 4-fold increase in post-IMP administration titer. |
Countries
United States
Outcome results
None listed