Study on Two Adjuvanted Dose Levels of Panblok H7+MF59 Compared for Immunogenicity and Safety With an Unadjuvanted Dose of Panblok H7 in Participants 18 Years of Age and Older

Study Overview
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Brief Summary
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VAM00001 is a Phase I/II, randomized, modified double-blind, multi-center study. The purpose of this study is to compare 2 dose levels of Panblok H7 (dose 1 and dose 2 of rHA) with a standard squalene dose of adjuvant MF59 to Panblok H7 (dose 3) unadjuvanted in approximately 700 adult participants in order to select one dose formulation to be used for further clinical development. The randomization ratio will be 3:3:1 for Panblok H7 (dose 1) + MF59, Panblok H7 (dose 2) + MF59, and Panblok H7 (dose 3) unadjuvanted, respectively. Each study group will be stratified into the age groups 18-64 years and ≥ 65 years of age. The study duration for each participant will be approximately 13 months.

Detailed Description
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The study duration for each participant will be approximately 13 months.

Official Title
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A Parallel-group, Phase I/II, Randomized, Modified Double-blind, 3-arm, Active Comparator, Multi-center, Prevention Study to Evaluate the Immunogenicity and Safety of Two Adjuvanted Dose Levels of Panblok H7+MF59 Influenza Vaccine Compared With an Unadjuvanted Dose of Panblok H7 in Participants 18 Years of Age and Older

Conditions
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Influenza Immunization, Healthy Volunteers

Intervention / Treatment
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* Biological: Panblok + MF59 Dose 1
* Biological: Panblok + MF59 Dose 2
* Biological: Unadjuvanted Panblok Dose 3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or older on the day of inclusion Participants who are healthy as determined by medical evaluation including medical history and physical examination A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, or surgically sterile. OR Is of childbearing potential and agrees to use a highly effective contraceptive method or abstinence from at least 4 weeks prior to each study intervention administration until at least 12 weeks after the last study intervention administration. A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 24 hours before the first dose of study intervention Informed consent form has been signed and dated Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances Thrombocytopenia or bleeding disorder contraindicating intramuscular injection based on investigator's judgement Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion (1) (1) Chronic illness may include, but is not limited to, cardiac disorders, renal disorders, auto-immune disorders, diabetes, psychiatric disorders, or chronic infection Neoplastic disease or any hematologic malignancy (except localized skin or prostate cancer that is stable at the time of study intervention administration in the absence of therapy, and participants who have a history of neoplastic disease and who have been disease-free for ≥ 5 years) Moderate or severe acute illness/infection (according to investigator judgment) or febrile illness (temperature ≥ 100.4°F) on the day of study intervention administration. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion Receipt of any vaccine in the 14 days preceding Visit 1 or planned receipt of any vaccine prior to Visit 3, except for seasonal flu vaccine, which may be received at least 2 weeks after Visit 2 Previous vaccination against H7N9 with an investigational vaccine Receipt of immune globulins, blood or blood-derived products in the past 3 months Participation at the time of study enrollment (or in the 4 weeks preceding the first study intervention administration) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study Personal or family history of Guillain-Barré syndrome Self-reported seropositivity for Hepatitis B antigen or Hepatitis C The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

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
Interventional Model Description: Eligible participants (18-64 years of age and ≥65 years of age) will be randomized in a 3:3:1 ratio to receive 2 doses, 21 days apart, by intramuscular (IM) route of either Panblok H7+MF59 (dose 1), Panblok H7+MF59 (dose 2), or unadjuvanted Panblok H7 (dose 3) at D01.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>2 doses, 21 days apart, of Panblok H7 dose 1 + MF59 | Biological: Panblok + MF59 Dose 1<br>* Pharmaceutical form: suspension for injection Route of administration: intramuscular<br>|
| Experimental: Group 2<br>2 doses, 21 days apart, of Panblok H7 dose 2 + MF59 | Biological: Panblok + MF59 Dose 2<br>* Pharmaceutical form: suspension for injection Route of administration: intramuscular<br>|
| Active Comparator: Group 3<br>2 doses, 21 days apart, of Panblok H7 dose 3 unadjuvanted | Biological: Unadjuvanted Panblok Dose 3<br>* Pharmaceutical form: liquid for injection Route of administration: intramuscular<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers of Hemagglutination inhibition (HAI) Antibody (Ab) titers in participants | HAI Ab titers obtained on Day 22 for comparison with Day 01, Day 202 and Day 387 by HIH measurement method | At Day 22 | 
| Geometric Mean Titers of Hemagglutination inhibition (HAI) Antibody (Ab) titers in participants | HAI Ab titers obtained on Day 43 for comparison with Day 01, Day 202 and Day 387 by HIH measurement method | At Day 43 | 
| Geometric Mean of individual Ratio (GMR) of HAI Ab titers in participants | Individual HAI Ab titers ratio Day 22/Day 01 (baseline) by HIH measurement method | At Day 22 | 
| Geometric Mean of individual Ratio (GMR) of HAI Ab titers in participants | Individual HAI Ab titers ratio Day 43/Day 01 (baseline) by HIH measurement method | At Day 43 | 
| Geometric Mean of individual Ratio (GMR) of HAI Ab titers in participants | Individual HAI Ab titers ratio Day 202/Day 01 (baseline) by HIH measurement method | At Day 202 | 
| Geometric Mean of individual Ratio (GMR) of HAI Ab titers in participants | Individual HAI Ab titers ratio Day 387/ Day 01 (baseline) by HIH measurement method | At Day 387 | 
| Percentage of participants with seroconversion | Seroconversion: defined as titer < 10 (1/dilution [1/dil]) on Day 01 and post-vaccination titer ≥ 40 (1/dil) on Day 22 or Day 43; or titer ≥ 10 (1/dil) on Day 01 and a ≥ 4-fold increase in titer (1/dil) on Day 22 or Day 43 Vaccination taking place on Day 01 and Day 22 by HIH measurement method | At 21 days after each vaccination | 
| Percentage of participants with HAI titer above predefined threshold | Participants with HAI Ab titers ≥ 40 (1/dil) by HIH measurement method | At Day 01 | 
| Percentage of participants with HAI titer above predefined threshold | Participants with HAI Ab titers ≥ 40 (1/dil) by HIH measurement method | At Day 22 | 
| Percentage of participants with HAI titer above predefined threshold | Participants with HAI Ab titers ≥ 40 (1/dil) by HIH measurement method | At Day 43 | 
| Percentage of participants with HAI titer above predefined threshold | Participants with HAI Ab titers ≥ 40 (1/dil) by HIH measurement method | At Day 202 | 
| Percentage of participants with HAI titer above predefined threshold | Participants with HAI Ab titers ≥ 40 (1/dil) by HIH measurement method | At Day 387 | 
| Percentage of participants with detectable HAI Ab titer | Detectable HAI Ab titer, ie, with a titer ≥ 10 (1/dil) by HIH measurement method | At Day 01 | 
| Percentage of participants with detectable HAI Ab titer | Detectable HAI Ab titer, ie, with a titer ≥ 10 (1/dil) by HIH measurement method | At Day 22 | 
| Percentage of participants with detectable HAI Ab titer | Detectable HAI Ab titer, ie, with a titer ≥ 10 (1/dil) by HIH measurement method | At Day 43 | 
| Percentage of participants with detectable HAI Ab titer | Detectable HAI Ab titer, ie, with a titer ≥ 10 (1/dil) by HIH measurement method | At Day 202 | 
| Percentage of participants with detectable HAI Ab titer | Detectable HAI Ab titer, ie, with a titer ≥ 10 (1/dil) by HIH measurement method | At Day 387 | 
| Geometric Mean Titers Ratio (GMTR) for Group1/Group3, Group2/Group3, and Group2/Group1 | Ratio of GMTs for Group1/Group3, Group2/Group3, and Group2/Group1 Vaccination taking place on Day 01 and Day 22 by HIH measurement method | At 21 days after each vaccination | 
| Geometric Mean Titers of Neutralization (NT) Ab titer in participants | Neutralization (NT) Ab titer obtained on Day 22 for comparison with D01, D202, and D387 by SN measurement method | At Day 22 | 
| Geometric Mean Titers of Neutralization (NT) Ab titer in participants | Neutralization (NT) Ab titer obtained on Day 43 for comparison with D01, D202, and D387 by SN measurement method | At Day 43 | 
| Geometric Mean of individual Ratio (GMR) of NT Ab titers in participants | Individual NT Ab titer ratio Day 22/Day 01 (baseline) by SN measurement method | At Day 22 | 
| Geometric Mean of individual Ratio (GMR) of NT Ab titers in participants | Individual NT Ab titer ratio Day 43/Day 01 (baseline) by SN measurement method | At Day 43 | 
| Geometric Mean of individual Ratio (GMR) of NT Ab titers in participants | Individual NT Ab titer ratio Day 202/Day 01 (baseline) by SN measurement method | At Day 202 | 
| Geometric Mean of individual Ratio (GMR) of NT Ab titers in participants | Individual NT Ab titer ratio Day 387/Day 01 (baseline) by SN measurement method | At Day 387 | 
| Percentage of participants with NT Ab titer above predefined threshold | Participants with NT Ab titers ≥ 20 (1/dil), ≥ 40 (1/dil), ≥ 80 (1/dil) on Day 22; compared to Day 01, Day 202, and Day 387 by SN measurement method | At Day 22 | 
| Percentage of participants with NT Ab titer above predefined threshold | Participants with NT Ab titers ≥ 20 (1/dil), ≥ 40 (1/dil), ≥ 80 (1/dil) on Day 43; compared to Day 01, Day 202, and Day 387 by SN measurement method | At Day 43 | 
| Percentage of participants with fold-increase in NT Ab titer | Fold-increase in NT Ab titer [post/pre] ≥ 2 and ≥ 4 on Day 22 and Day 43, as compared to D01 Vaccination taking place on Day 01 and Day 22 by SN measurement method | At 21 days after each vaccination | 
| Percentage of participants with detectable NT Ab titer | Detectable NT Ab titer, ie, with a titer ≥ 10 (1/dil) by SN measurement method | At Day 01 | 
| Percentage of participants with detectable NT Ab titer | Detectable NT Ab titer, ie, with a titer ≥ 10 (1/dil) by SN measurement method | At Day 22 | 
| Percentage of participants with detectable NT Ab titer | Detectable NT Ab titer, ie, with a titer ≥ 10 (1/dil) by SN measurement method | At Day 43 | 
| Percentage of participants with detectable NT Ab titer | Detectable NT Ab titer, ie, with a titer ≥ 10 (1/dil) by SN measurement method | At Day 202 | 
| Percentage of participants with detectable NT Ab titer | Detectable NT Ab titer, ie, with a titer ≥ 10 (1/dil) by SN measurement method | At Day 387 | 
| GMR for Group1/Group3, Group2/Group3, and Group2/Group1 | Ratio of GMs for Group1/Group3, Group2/Group3, and Group2/Group1 Vaccination taking place on Day 01 and Day 22 by SN measurement method | At 21 days after each vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with immediate adverse events (AEs) | Immediate adverse events are any unsolicited systemic adverse events | Within 30 minutes after each vaccination | 
| Number of participants with solicited injection site and systemic reactions | Solicited injection site reactions include injection site pain, erythema, swelling, induration, ecchymosis Solicited systemic reactions include fever, headache, malaise, myalgia | Up to 7 days after each/any vaccination | 
| Number of participants with unsolicited AEs | Unsolicited (spontaneously reported) AEs, not fulfilling criteria for solicited adverse reactions | Up to 21 days after each/any vaccination | 
| Number of participants with medically adverse events (MAAEs) | MAAEs | From Day 01 up to Day 387 | 
| Number of participants with adverse events of special interest (AESIs) | AESIs | From Day 01 up to Day 387 | 
| Number of participants with serious adverse events (SAEs) (including AESIs) | SAEs (including AESIs) | From Day 01 up to Day 387 |