Safety and Immunogenicity of Different Formulations of Monovalent Influenza A/Astrakhan/3212/2020 Like (H5N8) Virus Vaccine With AS03 Adjuvant System in Medically Stable Adults

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and immunogenicity of different formulations of monovalent Influenza A/Astrakhan/3212/2020-like virus vaccine with AS03 adjuvant system in adults greater than or equal to (>=)18 years of age.

Official Title
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A Phase I/II Observer-blind, Randomized, Multi-center Trial to Evaluate the Safety and Immunogenicity of Different Formulations of Monovalent Influenza A/Astrakhan/3212/2020 Like (H5N8) Virus Vaccine With AS03 Adjuvant System (Referred to as Q-Pan H5N8), Given as a Two-dose Series to Adults 18 to 64 Years of Age and 65 Years of Age and Older

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: FLU Q-PAN H5N8 Formulation 1
* Biological: AS03B
* Biological: AS03A
* Biological: FLU Q-PAN H5N8 Formulation 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Medically stable participants as established by medical history and clinical examination before entering into the study. A male or female >=18 years of age at the time of signing consent form. Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol. Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study specific procedure. Female participants of childbearing potential or non-childbearing potential may be enrolled in the study if specific criteria are met. Exclusion Criteria: Current diagnosis or history of autoimmune disorder(s) except hypothyroidism due to Hashimoto's thyroiditis. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. Clinically significant acute or chronic pulmonary, cardiovascular, hepatic, or renal disease that appears uncontrolled or untreated, as determined by history or physical examination. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history, physical examination, or abnormalities in screening blood tests. Recurrent history of or uncontrolled neurological disorders or seizures. History of Guillain-Barré syndrome. Diagnosed with cancer, or treatment for cancer within 3 years. Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible. Persons with a history of histologically confirmed basal cell carcinoma of the skin successfully treated with local excision only, are accepted and are eligible, but other histologic types of skin cancer are exclusionary. Women who are disease-free 3 years or more after treatment for breast cancer and receiving long-term prophylaxis are eligible. Documented human immunodeficiency virus-positive participants. Bedridden participants. Personal or family history of narcolepsy. Food and Drug Administration (FDA) toxicity Grade 2, or greater, laboratory tests at Screening. Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. Use of any investigational or non-registered product other than the study vaccine during the period beginning 30 days before the first dose of study vaccine (Day -29 to Day 1), or planned use during the entire study period. Use of public health emergency vaccines like coronavirus disease 2019 (COVID-19), Monkey pox (mpox) etc. These can be given at any time, but there should a gap of 2 - weeks before a dose of study vaccine can be given. Use of any licensed vaccines: prior to receipt of the study vaccine and continuing up to 3 weeks after receiving the dose 2 of study vaccine. Administration of long-acting immune-modifying drugs at any time during the study period. Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the first dose of study vaccine or planned administration during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine dose and through the entire study period. For corticosteroids, this will mean prednisone equivalent >=20 milligrams/day for 14 days or a total of >=280 mg of prednisone equivalent dose in any 14-day period. Inhaled and topical steroids are allowed. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions within 2 months after completion of the vaccination series. History of/or current drug/alcohol abuse. Any study personnel or their immediate dependents, family, or household member. 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 vaccine/product.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FLU Q-PAN H5N8 Formulation 1_B Group<br>Medically stable participants receive two doses of FLU Q-PAN H5N8 Formulation 1 vaccine and AS03B adjuvant. Participants receive the first dose at Day 1 and the second dose at Day 22. | Biological: FLU Q-PAN H5N8 Formulation 1<br>* Participants receive two doses of the FLU Q-PAN H5N8 Formulation 1 vaccine by intramuscular injection in the non-dominant arm.<br>Biological: AS03B<br>* Participants receive two doses of the AS03B adjuvant by intramuscular injection in the non-dominant arm.<br>|
| Active Comparator: FLU Q-PAN H5N8 Formulation 1_A Group<br>Medically stable participants receive two doses of FLU Q-PAN H5N8 Formulation 1 vaccine and AS03A adjuvant. Participants receive the first dose at Day 1 and the second dose at Day 22. | Biological: FLU Q-PAN H5N8 Formulation 1<br>* Participants receive two doses of the FLU Q-PAN H5N8 Formulation 1 vaccine by intramuscular injection in the non-dominant arm.<br>Biological: AS03A<br>* Participants receive two doses of the AS03A adjuvant by intramuscular injection in the non-dominant arm.<br>|
| Active Comparator: FLU Q-PAN H5N8 Formulation 2_B Group<br>Medically stable participants receive two doses of FLU Q-PAN H5N8 Formulation 2 vaccine and AS03B adjuvant. Participants receive the first dose at Day 1 and the second dose at Day 22. | Biological: AS03B<br>* Participants receive two doses of the AS03B adjuvant by intramuscular injection in the non-dominant arm.<br>Biological: FLU Q-PAN H5N8 Formulation 2<br>* Participants receive two doses of the FLU Q-PAN H5N8 Formulation 2 vaccine by intramuscular injection in the non dominant arm.<br>|
| Active Comparator: FLU Q-PAN H5N8 Formulation 2_A Group<br>Medically stable participants receive two doses of FLU Q-PAN H5N8 Formulation 2 vaccine and AS03A adjuvant. Participants receive the first dose at Day 1 and the second dose at Day 22. | Biological: AS03A<br>* Participants receive two doses of the AS03A adjuvant by intramuscular injection in the non-dominant arm.<br>Biological: FLU Q-PAN H5N8 Formulation 2<br>* Participants receive two doses of the FLU Q-PAN H5N8 Formulation 2 vaccine by intramuscular injection in the non dominant arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemagglutination-inhibiting (HI) antibody titers against vaccine-homologous H5N8 | HI antibody titers are expressed as GMTs. | At Day 43 | 
| Geometric mean fold rise (GMFR) of serum HI antibody titers against vaccine-homologous H5N8 | GMFR is defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. | At Day 43 | 
| Percentage of seroprotected (SP) participants for HI antibody titers | SP is defined as the percentage of participants with HI antibody titer >=1:40. | At Day 43 | 
| Percentage of participants reporting each solicited administration site event | Solicited administration site events are pain, redness and swelling. | Within the 7-day follow-up period after first study intervention dose (administered at Day 1) | 
| Percentage of participants reporting each solicited administration site event | Solicited administration site events are pain, redness and swelling. | Within the 7-day follow-up period after second study intervention dose (administered at Day 22) | 
| Percentage of participants reporting each solicited systemic event | Solicited systemic events are fatigue, fever, headache, joint pain, shivering (chills) Gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain). Fever is defined as temperature >=38 degrees Celsius (°C) for oral route (preferred location for measuring temperature). | Within the 7-day follow-up period after first study intervention dose (administered at Day 1) | 
| Percentage of participants reporting each solicited systemic event | Solicited systemic events are fatigue, fever, headache, joint pain, shivering (chills) Gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain). Fever is defined as temperature >=38 degrees Celsius (°C) for oral route (preferred location for measuring temperature). | Within the 7-day follow-up period after second study intervention dose (administered at Day 22) | 
| Percentage of participants with increased toxicity grading in either Hematological or Biochemical Laboratory Parameters | The following laboratory assessments includes Hematology; complete blood count with differential and platelet count; Chemistry/metabolic panel: Sodium, Potassium, Creatinine, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline Phosphatase, total bilirubin, and blood urea nitrogen (BUN) which are graded by FDA toxicity grading scale. Assessed grades are Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, and Grade 4 = potentially life threatening. | 7 days after the first study intervention dose (administered at Day 1) | 
| Percentage of participants with increased toxicity grading in either Hematological or Biochemical Laboratory Parameters | The following laboratory assessments includes Hematology; complete blood count with differential and platelet count; Chemistry/metabolic panel: Sodium, Potassium, Creatinine, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline Phosphatase, total bilirubin, and blood urea nitrogen (BUN) which are graded by FDA toxicity grading scale. Assessed grades are Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, and Grade 4 = potentially life threatening. | 7 days after the second study intervention dose (administered at Day 22) | 
| Percentage of participants reporting unsolicited adverse events (AEs) | An unsolicited AE is defined as any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms are reported as an unsolicited adverse event. | 21 days after the first study intervention dose (administered at Day 1) | 
| Percentage of participants reporting unsolicited AEs | An unsolicited AE is defined as any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms are reported as an unsolicited adverse event. | 21 days after the second study intervention dose (administered at Day 22) | 
| Percentage of participants reporting medically attended adverse events (MAEs) | MAE is defined as an AE that results in an unscheduled visit to a medical professional (e.g., symptoms or illnesses requiring a hospitalization, emergency room visit, or visit to/by a healthcare provider). | 21 days after the first study intervention dose (administered at Day 1) | 
| Percentage of participants reporting MAEs | MAE is defined as an AE that results in an unscheduled visit to a medical professional (e.g., symptoms or illnesses requiring a hospitalization, emergency room visit, or visit to/by a healthcare provider). | 21 days after the second study intervention dose (administered at Day 22) | 
| Percentage of participants reporting serious adverse events (SAEs) | 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, is an abnormal pregnancy outcome (e.g., spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy), or is a suspected transmission of any infectious agent via an authorized medicinal product. | From Day 1 to Day 43 | 
| Percentage of participants reporting SAEs | 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, is an abnormal pregnancy outcome (e.g., spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy), or is a suspected transmission of any infectious agent via an authorized medicinal product. | From Day 1 to 6 months after the second study intervention dose (administered at Day 22) | 
| Percentage of participants reporting potential immune-mediated diseases (pIMDs) | pIMDs are a subset of AEs of special interest that includes autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. | From Day 1 to Day 43 | 
| Percentage of participants reporting potential immune-mediated diseases (pIMDs) | pIMDs are a subset of AEs of special interest that includes autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. | From Day 1 to 6 months after the second study intervention dose (administered at Day 22) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HI antibody titers against vaccine-homologous H5N8 | HI antibody titers are expressed as GMTs. It is measured in terms of milliliter (mL). | Day 1, Day 22, and 6 months after the second intervention dose (administered at Day 22) | 
| GMFR of serum HI antibody titers against vaccine-homologous H5N8 | GMFR is defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. | At Day 22 and 6 months after the second intervention dose (administered at Day 22) | 
| Percentage of seroprotected participants for HI antibody titers | SP is defined as the percentage of participants with HI antibody titer >=1:40. | Day 1, Day 22, and 6 months after the second intervention dose (administered at Day 22) | 
| Percentage of seroconverted participants for HI antibody titers | HI seroconversion is defined as a post vaccination titer >=1:40 in the serum of participants with pre-vaccination titer below 1:10 or as a >=4-fold rise in post vaccination HI titer with pre-vaccination titer >=1:10. | Day 22, Day 43, and 6 months after the second study intervention dose (administered at Day 22) | 
| Microneutralization (MN) antibody titers for a subset of participants | MN antibody titers are expressed as Geometric Mean Titers (GMTs). MN analyses are performed on the MN subset that includes approximately 260 participants (50% of the planned enrolled participants). | Day 1, Day 22, 43, and 6 months after the second study intervention dose (administered at Day 22) | 
| Percentage of Seropositive participants for MN antibody titers for a subset of participants | A seropositive participant is a participant whose antibody titer is greater than or equal to the assay cut-off value. Note: The cut-off value for antibody titer is defined by the laboratory before the analysis. MN analyses is performed on the MN subset that includes approximately 260 participants (50% of the planned enrolled participants). | Day 1, Day 22, Day 43, and 6 months after the second intervention dose (administered at Day 22) | 
| Percentage of participants meeting vaccine response (VR) criteria of MN antibody titers for a subset of participants | MN VR is defined as titer >=4*Lower limit of quantitation (LLOQ) for participants with pre vaccination titer below LLOQ or as a >=4-fold increase in MN titer for participants with pre vaccination titer >=LLOQ. MN analyses are being performed on the MN subset that includes approximately 260 participants (50% of the planned enrolled participants). | Day 22, Day 43, and 6 months after the second study intervention dose (administered at Day 22) | 
| Percentage of seroprotected (SP) participants for HI antibody titers | SP is defined as the percentage of participants with HI antibody titer >=1:40. | Day 1, Day 22, and 6 months after the second intervention dose (administered at Day 22) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Safety, Immunogenicity