Adjuvanted Seasonal Recombinant QVLP Influenza Vaccine in Adults 65 Years of Age and Older
Study Details
Study Description
Brief Summary
This randomized, partially-blinded, active comparator-controlled will be conducted at multiple sites. The composition of QVLP to be used in this study includes a mix of recombinant H1, H3, and two B hemagglutinin proteins expressed as VLPs and will be based on the 2020-2021 influenza virus strains.
Approximately 120 healthy adult subjects 65 years of age and older are planned for randomization in a 1:1:1 ratio to receive QVLP at a dose of 30 µg/strain with AS03 adjuvant or QVLP (30 µg/strain) (unadjuvanted) or Fluzone HD Quad.
Subjects will participate in this study approximatly 12 months, during which a first visit will be scheduled on Day 0 for screening and vaccine administration.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Vaccine (30 µg/strain) adjuvanted with AS03 Treatment group 2: 30 µg/strain QVLP vaccine adjuvanted with AS03 |
Biological: Instramuscular vaccine
On Day 0, subjects will receive one intramuscular (IM) injection into the deltoid region of the non-dominant (if possible) arm.
|
| Active Comparator: Vaccine (30 µg/strain) unadjuvanted Treatment group 4: 30 µg/strain QVLP vaccine unadjuvanted |
Biological: Instramuscular vaccine
On Day 0, subjects will receive one intramuscular (IM) injection into the deltoid region of the non-dominant (if possible) arm.
|
| Active Comparator: Vaccine (60 µg/strain) Fluzone HD Quad Treatment group 5: 60 µg/strain Fluzone HD Quad vaccine |
Biological: Instramuscular vaccine
On Day 0, subjects will receive one intramuscular (IM) injection into the deltoid region of the non-dominant (if possible) arm.
|
Outcome Measures
Primary Outcome Measures
- Immediate adverse event (AEs) [30 minutes]
Percentage, intensity and relationship to vaccination of immediate adverse events (AEs)
- Solicited local and systemic adverse events (AEs) [Day 7]
Percentage and intensity of solicited local and systemic adverse events (AEs) following vaccination
- Unsolicited adverse events (AEs) [Day 28]
Percentage, intensity and relationship of unsolicited adverse events (AEs) following vaccination
- Safety labs [Day 3]
Number of subjects with normal and abnormal, clinically significant urine, haematological and blood biochemistry values, and urinalysis
- Safety labs [Day 3]
Percentage of subjects with normal and abnormal, clinically significant urine, haematological and blood biochemistry values, and urinalysis
- Safety labs [Day 28]
Number of subjects with normal and abnormal, clinically significant urine, haematological and blood biochemistry values, and urinalysis
- Safety labs [Day 28]
Percentage of subjects with normal and abnormal, clinically significant urine, haematological and blood biochemistry values, and urinalysis
- Serious adverse events (SAEs), adverse events (AEs) leading to withdrawal, adverse events of special interest (AESIs), medically attended adverse event (MAAEs), new onset of chronic disease (NOCDs) and deaths [Day 0 to 365]
Occurrences of serious adverse events (SAEs), adverse events (AEs) leading to withdrawal, adverse events of special interest (AESIs), medically attended adverse event (MAAEs), new onset of chronic disease (NOCDs) and deaths
- HI antibody response induced by adjuvanted and unadjuvanted QVLP and Fluzone HD Quad against the homologous influenza strain [Day 28]
HI antibody response induced by adjuvanted and unadjuvanted QVLP and Fluzone HD Quad against the homologous influenza strains on Day 28, compared to Day 0 values. HI antibody titers will be analyzed using the following parameters: geometric mean titers (GMT), seroconversion (SC) rate, seroprotection (SP) rate, and geometric mean fold rise (GMFR).
Secondary Outcome Measures
- MN antibody response induced by adjuvanted and unadjuvanted QVLP and Fluzone HD Quad against the homologous influenza strains [Day 28]
MN antibody response induced by adjuvanted and unadjuvanted QVLP and Fluzone HD Quad against the homologous influenza strains on Day 28, compared to Day 0 values. MN antibody titers will be analyzed using the following parameters: GMT, SC rate, and GMFR
- HI antibody response induced by adjuvanted and unadjuvanted QVLP and Fluzone HD Quad against the heterologous influenza strains [Day 28]
HI antibody response induced by adjuvanted and unadjuvanted QVLP and Fluzone HD Quad against the heterologous influenza strains on Day 28, compared to Day 0 values. HI antibody titers will be analyzed using the following parameters: GMT, SC rate, SP rate, and GMFR
- Durability of antibody responses [12 months]
Durability of antibody responses, as determined by HI and MN titers against homologous influenza strains (6 and 12 months post-vaccination)
- Immediate adverse event (AEs) [30 minutes]
Percentage, intensity and relationship to vaccination of immediate adverse events (AEs) stratified by prior influenza vaccination status, if >25% of the enrolled subjects have received a standard influenza vaccine the 12 months prior to study vaccination
- Solicited local and systemic adverse events (AEs) [7 days]
Percentage and intensity of solicited local and systemic adverse events (AEs) following vaccination stratified by prior influenza vaccination status, if >25% of the enrolled subjects have received a standard influenza vaccine during the 12 months prior to study vaccination
- Unsolicited adverse events (AEs) [28 days]
Percentage, intensity and relationship of unsolicited adverse events (AEs) following vaccination stratified by prior influenza vaccination status, if >25% of the enrolled subjects have received a standard influenza vaccine during the 12 months prior to study vaccination
- Safety labs [Day 3]
Number of subjects with normal and abnormal, clinically significant urine, haematological and blood biochemistry values, and urinalysis stratified by prior influenza vaccination status, if >25% of the enrolled subjects have received a standard influenza vaccine during the 12 months prior to study vaccination
- Safety labs [Day 3]
Percentage of subjects with normal and abnormal, clinically significant urine, haematological and blood biochemistry values, and urinalysis stratified by prior influenza vaccination status, if >25% of the enrolled subjects have received a standard influenza vaccine during the 12 months prior to study vaccination
- Safety labs [Day 28]
Number of subjects with normal and abnormal, clinically significant urine, haematological and blood biochemistry values, and urinalysis stratified by prior influenza vaccination status, if >25% of the enrolled subjects have received a standard influenza vaccine during the 12 months prior to study vaccination
- Safety labs [Day 28]
Percentage of subjects with normal and abnormal, clinically significant urine, haematological and blood biochemistry values, and urinalysis stratified by prior influenza vaccination status, if >25% of the enrolled subjects have received a standard influenza vaccine during the 12 months prior to study vaccination
- Serious adverse events (SAEs), adverse events (AEs) leading to withdrawal, adverse events of special interest (AESIs), medically attended adverse event (MAAEs), new onset of chronic disease (NOCDs) and deaths [Day 0 to 365]
Occurrences of serious adverse events (SAEs), adverse events (AEs) leading to withdrawal, adverse events of special interest (AESIs), medically attended adverse event (MAAEs), new onset of chronic disease (NOCDs) and deaths stratified by prior influenza vaccination status, if >25% of the enrolled subjects have received a standard influenza vaccine during the 12 months prior to study vaccination
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subjects must have read, understood, and signed the informed consent form (ICF) prior to participating in the study; subjects must also complete study-related procedures and communicate with the study staff at visits and by phone during the study;
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Male and female subjects must be 65 years of age and older at the Vaccination visit (Visit 2);
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Subject must have a body mass index (BMI) < 30 kg/m2 at the Vaccination visit (Visit 2);
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Subjects are considered by the Investigator to be reliable and likely to cooperate with the assessment procedures and be available for the duration of the study;
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Subjects must be non-institutionalized (e.g. not living in rehabilitation centres or old-age homes; living in an elderly community is acceptable) and have no acute or evolving medical problems prior to study participation and no clinically relevant abnormalities that could jeopardize subject safety or interfere with study assessments, as assessed by the Principal Investigator or sub-Investigator (thereafter referred as Investigator) and determined by medical history, physical examination, serology, clinical chemistry and haematology tests, urinalysis, and vital signs. Investigator discretion will be permitted with this inclusion criterion;
Note: Subjects with a pre-existing chronic disease will be allowed to participate if the disease is stable and, according to the Investigator's judgment that must be documented in the source documents, the condition is unlikely to confound the results of the study or pose additional risk to the subject by participating in the study. Stable disease is generally defined as no new onset or exacerbation of pre-existing chronic disease three months prior to vaccination. Based on the Investigator's judgment and documented in source documentation, a subject with more recent stabilization of a disease could also be eligible.
Exclusion Criteria:
- According to the Investigator's opinion, significant acute or chronic, uncontrolled medical or neuropsychiatric illness. Acute disease is defined as presence of any moderate or severe acute illness with or without a fever within 48 hours prior to the
Vaccination visit (Visit 2). 'Uncontrolled' is defined as:
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Requiring a new medical or surgical treatment during the three months prior to study vaccine administration;
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Requiring any significant change in a chronic medication (i.e. drug, dose, frequency) during the three months prior to study vaccine administration due to uncontrolled symptoms or drug toxicity unless the innocuous nature of the medication change meets the criteria outlined in inclusion criterion no. 5 and is appropriately justified and documented by the Investigator.
Investigator discretion is permitted with this exclusion criterion and must be carefully and fully documented in the source documents.
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Any confirmed or suspected current immunosuppressive condition or immunodeficiency, including cancer, human immunodeficiency virus, hepatitis B or C infection (subjects with a history of cured hepatitis B or C infection without any signs of immunodeficiency at present time are allowed). Investigator discretion is permitted with this exclusion criterion;
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Current autoimmune disease requiring systemic treatment (such as rheumatoid arthritis, systemic lupus erythematosus, or multiple sclerosis). Investigator discretion is permitted with this exclusion criterion, and subjects may be eligible to participate with appropriate written justification in the source document (i.e. subjects with a history of autoimmune disease who are disease-free without treatment for three years or more, or on stable thyroid replacement therapy, mild psoriasis [i.e. a small number of minor plaques requiring no systemic treatment], etc.);
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Administration of any non-influenza vaccine within 30 days prior to the Vaccination visit (Visit 2); planned administration of any vaccine up to Day 28 of the study. Immunization on an emergency basis during the study will be evaluated on case-by-case basis by the Investigator.
Note: Administration of an authorized COVID-19 vaccine prior to or during the study is acceptable;
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Administration of influenza vaccine within six months prior to the Vaccination visit (Visit 2) or planned administration of influenza vaccine (other than the study vaccine) up to completion of the study;
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Administration of any adjuvanted or investigational influenza vaccine within one year prior to randomization or planned administration prior to the completion of the study;
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Use of any investigational or non-registered product within 30 days or five half-lives, whichever is longer, prior to the Vaccination visit (Visit 2) or planned use during the study period. Subjects who are in a prolonged post-administration observation period of another investigational or marketed drug clinical study, for which there is no ongoing exposure to the investigational or marketed product and all scheduled on-site visits are completed, will be allowed to take part in this study, if all other eligibility criteria are met;
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Administration of any medication or treatment that may alter the vaccine immune responses, such as:
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Systemic glucocorticoids at a dose exceeding 10 mg of prednisone (or equivalent) per day for more than seven consecutive days or for 10 or more days in total, within one month prior to the Vaccination visit (Visit 2). Inhaled, nasal, intraarticular, ophthalmic, dermatological, and other topical glucocorticoids are permitted;
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Cytotoxic, antineoplastic or immunosuppressant drugs - within 36 months prior to the Vaccination visit (Visit 2);
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Any immunoglobulin preparations or blood products, blood transfusion - within 6 months prior to the Vaccination visit (Visit 2);
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Use of any prescription antiviral drugs with the intention of COVID-19 prophylaxis, including those that are thought to be effective for prevention of COVID-19 but have not been licensed for this indication, within one month prior to the Vaccination visit (Visit 2);
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Subjects at high risk of contracting SARS-CoV-2/COVID-19 infection, including, but not limited to, individuals with known close contact with:
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anyone residing in, visiting, or working at a health care or long-term care institution (i.e. long-term care facilities, acute care hospitals, rehabilitation hospitals, mental health hospitals, emergency departments);
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anyone with laboratory-confirmed SARS-CoV-2/COVID-19 infection within 2 weeks prior to vaccine administration;
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anyone who traveled outside the country for any duration within 30 days before the study vaccination;
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History of allergy to any of the constituents of QVLP, any components of Fluzone HD Quad, the adjuvant AS03, egg, or tobacco;
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History of anaphylactic allergic reactions to plants or plants components (including fruits and nuts);
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Subjects with a history of Guillain-Barré Syndrome;
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Personal or family (first-degree relatives) history of narcolepsy;
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Use of prophylactic medications (e.g. antihistamines [H1 receptor antagonists], nonsteroidal anti-inflammatory drugs [NSAIDs], systemic and topical glucocorticoids, non-opioid and opioid analgesics) within 24 hours prior to the Vaccination visit (Visit 2) to prevent or pre-empt symptoms due to vaccination;
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Have a rash, dermatological condition, tattoos, muscle mass, or any other abnormalities at the injection site that may interfere with injection site reaction rating. Investigator discretion will be permitted with this exclusion criterion;
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Subjects identified as an Investigator or employee of the Investigator or clinical site with direct involvement in the proposed study, or identified as an immediate family member (i.e. parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study, or any employees of Medicago.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Optimal Sites | Huntsville | Alabama | United States | 35802-2569 |
| 2 | Synexus | Chandler | Arizona | United States | 85224 |
| 3 | Optimal Sites | San Diego | California | United States | 92108 |
| 4 | Optimal Sites | Melbourne | Florida | United States | 32934-8172 |
| 5 | Global AES | Orlando | Florida | United States | 32806 |
| 6 | Global AES | The Villages | Florida | United States | 32162-7116 |
| 7 | Optimal Sites | Peoria | Illinois | United States | 61614 |
| 8 | Synexus | Evansville | Indiana | United States | 47714-7513 |
| 9 | Optimal Sites | Rockville | Maryland | United States | 20850 |
| 10 | Vitalink Research | Anderson | South Carolina | United States | 29621 |
| 11 | Vitalink Research | Columbia | South Carolina | United States | 29204 |
| 12 | Vitalink Research | Gaffney | South Carolina | United States | 29340 |
| 13 | Vitalink Research | Union | South Carolina | United States | 29379 |
| 14 | Optimal Sites | Austin | Texas | United States | 78705-2655 |
Sponsors and Collaborators
- Medicago
Investigators
- Study Director: Brian J Ward, MD, Medicago
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CP-PRO-AdjQVLP-020