Efficacy, Immunogenicity and Safety of OVX836 Influenza Vaccine 480μg

Study Overview
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Brief Summary
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The present study will evaluate the efficacy, immunogenicity and safety of one dose of OVX836 influenza vaccine 480μg, after intramuscular administration in healthy subjects aged 18-55 years.

Detailed Description
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This Phase 2b proof-of-concept field efficacy study is designed as a randomized, double-blind, parallel groups, placebo-controlled, multi-country, multicenter clinical trial, with adaptive design in terms of number of subjects vaccinated and influenza seasons followed-up. This design of prospective interventional trial is the gold standard in evaluating absolute efficacy of a product in preventing a disease or an outcome. An adequate number of observations is ensured by the multicenter approach.

Official Title
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Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Immunogenicity and Safety of One Dose of OVX836 Influenza Vaccine 480μg, After Intramuscular Administration in Healthy Subjects Aged 18-55 Years

Conditions
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Influenza

Intervention / Treatment
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* Biological: OVX836 480µg
* Biological: Saline Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Healthy male or female subjects, as determined by medical history and medical examination. Between the ages of 18 and 55 years, inclusive. Reliable and willing to make themselves available for the duration of the study, and willing and able to follow study procedures Able to read, understand and complete an electronic Diary and electronic Patient Reported Outcome, and availability of a person who can complete the electronic Diary/electronic Patient Reported Outcome in case of illness. Exclusion Criteria: Previous influenza vaccination within 6 months before the day of vaccination or planned to receive influenza vaccination during the whole study period. Formal indication for influenza vaccination on an individual basis according to local recommendations, for example based on occupational risk, or underlying medical conditions. Any known or suspected immunodeficient conditions. Past or current history of significant autoimmune diseases, as judged by the Investigator. Known or suspected infection with human immunodeficiency virus, hepatitis C virus, or hepatitis B virus. Current history of significant uncontrolled medical illness such as diabetes, hypertension, heart, renal or hepatic diseases, as judged by the Investigator. Planned gender reassignment during the study. Having received another vaccination within 3 months prior to the day of study vaccination for live attenuated vaccines, or within 1 month prior to the day of study vaccination for inactivated vaccines, except Severe Acute Respiratory Syndrome Coronavirus-2 (COVID-19) vaccine. Planning to receive other vaccines during the first 28 days following the study vaccine administration. Having received a COVID-19 vaccination within 2 weeks prior to the day of study vaccination. Planning to receive COVID-19 vaccine during the first week (within 7 days) following the study vaccine administration. An interval of preferably 14 days is recommended. If for scheduling reasons, COVID-19 vaccine has to be given on Day 8, the vaccination should be administered after completion of the study procedures. Administration of any investigational or non-registered drug or vaccine within 3 months prior to the administration of study vaccines, or planned administration of any such product during the whole study period. History of receiving blood, blood components or immunoglobulins within 3 months prior to the day of vaccination, or planned to receive such product during the whole study period. Presence of an acute febrile illness on the day of planned vaccination (oral temperature >38.0°C; temporary exclusion criterion). Ongoing or recently recovered long COVID. Presence of a condition in the ear-nose-throat area, such as nasal septum deviation, atrophic rhinitis, etc…, that could render nasal and nasopharyngeal swabs more difficult to perform, or increase the risk of bleeding; to be confirmed by medical history question and inspection of nasal passage. Past or current history of any progressive or severe uncontrolled neurological disorder, seizure disorder or Guillain-Barré syndrome. Behavioral or cognitive impairment, or psychiatric disease that, in the opinion of the Investigator, may interfere with the subject's ability to participate in the study. Past (stopped less than 6 months before enrolment) or current smoking habit above 10 cigarettes per day. Past (stopped less than 6 months before enrolment) or current history of alcohol abuse or use of recreational drugs. Treatment that can affect immune response such as systemic or high dose inhaled corticosteroids (>800 μg/day beclomethasone or equivalent; occasional inhaled corticosteroids for asthma therapy are allowed), radiation treatment, cytotoxic drugs, or current or recent (within 30 days before study entry) chronic or prolonged (>10 days) use of systemic non-steroidal anti-inflammatory drugs, acetylsalicylic acid, paracetamol, ibuprofen, interferon, immunomodulators, allergy shots, as judged by the Investigator. Occasional, non-continuous use of acetylsalicylic acid, paracetamol, ibuprofen or non-steroidal anti-inflammatory drugs on an as-needed basis is allowed. Prophylactic or therapeutic use of any anti(retro)virals during the study. History of severe allergic reactions and/or anaphylaxis, or serious adverse reactions to vaccines or allergy to kanamycin. Any contraindication to intramuscular administration, as judged by the Investigator. Individuals with history of any illness that, in the opinion of the Investigator, might interfere with the results of the study, or pose additional risk to the subjects due to participation in the study, either directly or through any treatments administered for that illness. Technical difficulties or other inability to use of an eDiary. Sponsor employees or Investigator site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse (or assimilated), parent, child or sibling, whether biological or legally adopted.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: A total number of 1,500 subjects are planned to be randomized (in a 1:1 ratio) into 2 groups to receive a single intramuscular injection of either OVX836 (480μg) or placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OVX836 480µg<br>Adjuvant-free recombinant influenza candidate vaccine based on Nucleoprotein in the influenza virus. One single administration intramuscularly of 480µg dose on Day1. | Biological: OVX836 480µg<br>* One single administration intramuscularly at Day 1.<br>|
| Placebo Comparator: Placebo<br>Saline solution (B. Braun Ecoflac Plus) Saline solution (Nacl 0.9%), B. Braun Ecoflac Plus 50mL. One single administration intramuscularly of a 0.8mL dose on Day1. | Biological: Saline Solution<br>* One single administration intramuscularly at Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First occurrence of RT-PCR-confirmed influenza Type A symptomatic disease |  | During the whole study duration, up to 270 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First occurrence of RT-PCR-confirmed influenza symptomatic disease irrespective of strain/type. |  | During the whole study duration, up to 270 daysDuring the whole study duration, up to 270 days | 
| First of occurrence of RT-PCR-confirmed influenza Type B symptomatic disease |  | During the whole study duration, up to 270 days | 
| Number of subtype of virus in RT-PCR-confirmed influenza Type A cases. |  | During the whole study duration, up to 270 days | 
| Severity and duration of Influenza Like Illness episodes |  | During the whole study duration, up to 270 days | 
| First occurence of clinical influenza-like disease irrespective of causal agent |  | During the whole study duration, up to 270 days | 
| Number of occurence of solicited local and systemic signs and symptoms |  | During 7 days after vaccine administration | 
| Number of occurence of subjects reporting unsolicited AEs |  | During 29 days after vaccine administration | 
| Number of occurence of subjects reporting Serious Adverse Events |  | During the whole study period, 270 days | 
| Cell-mediated immune response in Peripheral Blood Mononuclear Cells, measured by Interferon Gamma Enzyme-Linked Immunospot Assay. | Elispot | At Day 1, Day 8 and Day 29 | 
| Number and percentage of subjects with NP-specific T-cell measured by Interferon Gamma Enzyme-Linked Immunospot Assay. | Elispot | At Day 8 and Day 29 | 
| Percentage of NP specific CD4+ and CD8+ T-cell measured by flow cytometry on PBMCs as expressing IL-2, TNFα and/or IFNγ at pre-injection baseline (Day 1) | ICS | At Day 1 and Day 8 | 
| Number and percentage of subjects with a percentage of NP specific CD4+ and CD8+ T-cell expressing IL-2, TNFα and/or IFNγ at Day 8 or Day 29 higher than the percentile 95 of the pre-injection baseline (Day 1) | ICS | At Day 8 and Day 29 | 
| Geometric Mean Titer of anti-Nucleoprotein immunoglobulin G (Enzyme-Linked Immunosorbent Assay, serum). | Elisa | At Day 1, Day 8 and Day 29 | 
| Number and percentage of subjects with a four-fold increase of anti-Nucleoprotein immunoglobulin G (Enzyme-Linked Immunosorbent Assay, serum) titre with respect to pre-injection baseline (Day 1) | Elisa | At Day 8 and Day 29 |