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 Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: FLU Q-PAN H5N8 Formulation 1_B Group 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
Participants receive two doses of the FLU Q-PAN H5N8 Formulation 1 vaccine by intramuscular injection in the non-dominant arm.
Biological: AS03B
Participants receive two doses of the AS03B adjuvant by intramuscular injection in the non-dominant arm.
|
| Active Comparator: FLU Q-PAN H5N8 Formulation 1_A Group 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
Participants receive two doses of the FLU Q-PAN H5N8 Formulation 1 vaccine by intramuscular injection in the non-dominant arm.
Biological: AS03A
Participants receive two doses of the AS03A adjuvant by intramuscular injection in the non-dominant arm.
|
| Active Comparator: FLU Q-PAN H5N8 Formulation 2_B Group 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
Participants receive two doses of the AS03B adjuvant by intramuscular injection in the non-dominant arm.
Biological: FLU Q-PAN H5N8 Formulation 2
Participants receive two doses of the FLU Q-PAN H5N8 Formulation 2 vaccine by intramuscular injection in the non dominant arm.
|
| Active Comparator: FLU Q-PAN H5N8 Formulation 2_A Group 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
Participants receive two doses of the AS03A adjuvant by intramuscular injection in the non-dominant arm.
Biological: FLU Q-PAN H5N8 Formulation 2
Participants receive two doses of the FLU Q-PAN H5N8 Formulation 2 vaccine by intramuscular injection in the non dominant arm.
|
Outcome Measures
Primary Outcome Measures
- Hemagglutination-inhibiting (HI) antibody titers against vaccine-homologous H5N8 [At Day 43]
HI antibody titers are expressed as GMTs.
- Geometric mean fold rise (GMFR) of serum HI antibody titers against vaccine-homologous H5N8 [At Day 43]
GMFR is defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination.
- Percentage of seroprotected (SP) participants for HI antibody titers [At Day 43]
SP is defined as the percentage of participants with HI antibody titer >=1:40.
- Percentage of participants reporting each solicited administration site event [Within the 7-day follow-up period after first study intervention dose (administered at Day 1)]
Solicited administration site events are pain, redness and swelling.
- Percentage of participants reporting each solicited administration site event [Within the 7-day follow-up period after second study intervention dose (administered at Day 22)]
Solicited administration site events are pain, redness and swelling.
- Percentage of participants reporting each solicited systemic event [Within the 7-day follow-up period after first study intervention dose (administered at Day 1)]
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).
- Percentage of participants reporting each solicited systemic event [Within the 7-day follow-up period after second study intervention dose (administered at Day 22)]
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).
- Percentage of participants with increased toxicity grading in either Hematological or Biochemical Laboratory Parameters [7 days after the first study intervention dose (administered at Day 1)]
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.
- Percentage of participants with increased toxicity grading in either Hematological or Biochemical Laboratory Parameters [7 days after the second study intervention dose (administered at Day 22)]
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.
- Percentage of participants reporting unsolicited adverse events (AEs) [21 days after the first study intervention dose (administered at Day 1)]
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.
- Percentage of participants reporting unsolicited AEs [21 days after the second study intervention dose (administered at Day 22)]
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.
- Percentage of participants reporting medically attended adverse events (MAEs) [21 days after the first study intervention dose (administered at Day 1)]
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).
- Percentage of participants reporting MAEs [21 days after the second study intervention dose (administered at Day 22)]
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).
- Percentage of participants reporting serious adverse events (SAEs) [From Day 1 to Day 43]
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.
- Percentage of participants reporting SAEs [From Day 1 to 6 months after the second study intervention dose (administered at Day 22)]
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.
- Percentage of participants reporting potential immune-mediated diseases (pIMDs) [From Day 1 to Day 43]
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.
- Percentage of participants reporting potential immune-mediated diseases (pIMDs) [From Day 1 to 6 months after the second study intervention dose (administered at Day 22)]
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.
Secondary Outcome Measures
- HI antibody titers against vaccine-homologous H5N8 [Day 1, Day 22, and 6 months after the second intervention dose (administered at Day 22)]
HI antibody titers are expressed as GMTs. It is measured in terms of milliliter (mL).
- GMFR of serum HI antibody titers against vaccine-homologous H5N8 [At Day 22 and 6 months after the second intervention dose (administered at Day 22)]
GMFR is defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination.
- Percentage of seroprotected (SP) participants for HI antibody titers [Day 1, Day 22, and 6 months after the second intervention dose (administered at Day 22)]
SP is defined as the percentage of participants with HI antibody titer >=1:40.
- Percentage of seroconverted participants for HI antibody titers [Day 22, Day 43, and 6 months after the second study intervention dose (administered at Day 22)]
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.
- Microneutralization (MN) antibody titers for a subset of participants [Day 1, Day 22, 43, and 6 months after the second study intervention dose (administered at Day 22)]
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).
- Percentage of Seropositive participants for MN antibody titers for a subset of participants [Day 1, Day 22, Day 43, and 6 months after the second intervention dose (administered at Day 22)]
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).
- Percentage of participants meeting vaccine response (VR) criteria of MN antibody titers for a subset of participants [Day 22, Day 43, and 6 months after the second study intervention dose (administered at Day 22)]
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).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Medically stable participants as established by medical history and clinical examination before entering into the study.
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A male or female >=18 years of age at the time of signing consent form.
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Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
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Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study specific procedure.
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Female participants of childbearing potential or non-childbearing potential may be enrolled in the study if specific criteria are met.
Exclusion Criteria:
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Current diagnosis or history of autoimmune disorder(s) except hypothyroidism due to Hashimoto's thyroiditis.
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History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
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Clinically significant acute or chronic pulmonary, cardiovascular, hepatic, or renal disease that appears uncontrolled or untreated, as determined by history or physical examination.
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Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history, physical examination, or abnormalities in screening blood tests.
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Recurrent history of or uncontrolled neurological disorders or seizures.
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History of Guillain-Barré syndrome.
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Diagnosed with cancer, or treatment for cancer within 3 years.
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Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible.
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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.
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Women who are disease-free 3 years or more after treatment for breast cancer and receiving long-term prophylaxis are eligible.
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Documented human immunodeficiency virus-positive participants.
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Bedridden participants.
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Personal or family history of narcolepsy.
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Food and Drug Administration (FDA) toxicity Grade 2, or greater, laboratory tests at Screening.
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Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.
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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.
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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.
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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.
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Administration of long-acting immune-modifying drugs at any time during the study period.
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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.
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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.
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Pregnant or lactating female.
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Female planning to become pregnant or planning to discontinue contraceptive precautions within 2 months after completion of the vaccination series.
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History of/or current drug/alcohol abuse.
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Any study personnel or their immediate dependents, family, or household member.
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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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- GlaxoSmithKline
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 219833