INFLUENZA A (H1N1/WSN/1933) NUCLEOPROTEIN FUSED TO C-TERMINAL FRAGMENTS OF TWO AVIAN C4BP ALFA CHAIN SEQUENCES for Influenza

Inclusion criteria

• {"criterion_text":"- Written informed consent\n- Healthy male or female subjects, as determined by medical history and medical examination.\n- Between the ages of 18 and 59 years, inclusive\n- Subjects compliant with the reproductive criteria for male and female participants\n- Reliable and willing to make themselves available for the duration of the study, and willing and able to follow study procedures\n- Able to read, understand, and complete an eDiary and electronic patient-reported outcome (ePRO)\n- Subject socially active: living in a family with children or with other house-hold members, having frequent social contacts at university, work, in public places such as restaurants, theaters, public transportation, etc.\n- Able to read and sign the subject information sheet and informed consent form (ICF)."}

Exclusion criteria

• {"criterion_text":"- Previous vaccination with an authorized or experimental seasonal, zoonotic or pandemic influenza vaccine within 6 months before the day of vaccination or planned to receive it during the whole study period\n- Prophylactic or therapeutic use of influenza antivirals within 7 days prior to the day of study vaccination or during the whole study duration.\n- History of severe allergic reactions and/or anaphylaxis, or serious adverse reactions to vaccines or allergy to kanamycin or any other component of the OVX836 vaccine\n- Females planning to become pregnant or planning to discontinue contraceptive precautions until the end of the trial\n- Any contraindication to intramuscular administration, as judged by the Investigator\n- Presence of extended tattoos on both deltoid muscles\n- Individuals with a 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\n- Any known or suspected immunodeficient conditions\n- 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\n- Having received another vaccine within 1 month prior to the day of study vaccination, except COVID-19 vaccines for which the minimum time period should be two weeks prior to study vaccination\n- Planned absences without access to the investigational site, i.e. vacation or business trips, for more than 7 consecutive days during the study period\n- Presence of an acute febrile illness on the day of planned vaccination (oral temperature ≥37.5°C; temporary exclusion criterion).\n- Any medical illness such as diabetes, hypertension, heart, renal, or hepatic diseases, as judged by the Investigator\n- Pregnant or lactating woman\n- Having received 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.\n- Past (stopped less than 6 months before enrolment) or current smoking habit above 10 cigarettes per day.\n- Past (stopped less than 6 months before enrolment) or current history of heavy alcohol use, defined as follows: for men, consumption of more than 4 standard drinks on any day or more than 14 standard drinks per week, and for women, consumption of more than 3 standard drinks on any day or more than 7 standard drinks per week.\n- Past (stopped less than 6 months before enrolment) or current use of recreational drugs, which could interfere with the adherence to the protocol procedures\n- Chronic or prolonged treatment (>10 consecutive days) that can affect immune response, such as systemic (≥ 20 mg/day prednisone or equivalent or dexamethasone >4 mg/day), high dose inhaled corticosteroids (>800 μg/day beclomethasone or equivalent; occasional inhaled, topical or localized injections [intra-articular or intra-bursal] of corticosteroids for asthma therapy are allowed), or immunomodulators/suppressors (certain monoclonal antibodies can be approved on a case by case basis) within 28 days before study entry or during the whole study duration\n- Chronic or prolonged (>10 days) use of systemic non-steroidal anti-inflammatory drugs, acetylsalicylic acid, or paracetamol within 7 days before study entry and up to 28 days post-vaccination\n- 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.\n- Past (stopped less than 6 months before enrolment) or current smoking habit above 10 cigarettes per day.\n- Diagnosed long COVID-19 subjects\n- Presence of a condition in the ear-nose-throat area, such as nasal septum deviation, atrophic rhinitis, etc…, that could render nasopharyngeal swabs more difficult to perform, or increase the risk of bleeding; to be confirmed by medical history question and inspection of nasal passage\n- Behavioral or cognitive impairment, or psychiatric disease including suicidal ideation that, in the opinion of the Investigator, may interfere with the subject's ability to participate throughout the whole duration of the study\n- Having participated or currently participating in an OVX836 study, except the current OVX836-005 study, or in the OVX-FLU-002 study\n- Formal indication for influenza vaccination on an individual basis according to local recommendations, e.g. based on occupational risk (health care workers), or underlying medical conditions. An informed subject who would refuse to get the regular influenza vaccination would be allowed to participate in this study\n- Past (stopped less than 6 months before enrolment) or current history of heavy alcohol use, defined as follows: for men, consumption of more than 4 standard drinks on any day or more than 14 standard drinks per week, and for women, consumption of more than 3 standard drinks on any day or more than 7 standard drinks per week.\n- Chronic or prolonged (>10 days) use of systemic non-steroidal anti-inflammatory drugs, acetylsalicylic acid, or paracetamol within 7 days before study entry and up to 28 days post-vaccination\n- History of severe allergic reactions and/or anaphylaxis, or serious adverse reactions to vaccines or allergy to kanamycin or any other component of the OVX836 vaccine\n- Current or past history of progressive or severe uncontrolled neurological disorder, or current or past history of seizure disorder or Guillain-Barré syndrome\n- Females planning to become pregnant or planning to discontinue contraceptive precautions until the end of the trial\n- Any contraindication to intramuscular administration, as judged by the Investigator"}

Primary endpoints

• {"endpoint_text":"- First occurrence of RT-PCR-confirmed influenza Type A illness, from 14 days after vaccination, characterized by the presence of one or more of the following respiratory symptoms (sore throat, cough, sputum production, wheezing, difficulty breathing), concurrent with one or more of the following systemic symptoms (temperature ≥37.5°C, chills, tiredness, headache or myalgia), lasting for at least 24 hours.","definition_or_measurement_approach":"RT-PCR-confirmed influenza Type A illness occurring from 14 days after vaccination; requires specific respiratory and systemic symptom combination lasting ≥24 hours; laboratory confirmation by RT-PCR."}

Secondary endpoints

• {"endpoint_text":"- First occurrence of laboratory-confirmed (RT-PCR-confirmed cases and in RT-PCR + culture-confirmed cases) influenza Type A symptomatic illness, from 14 days after vaccination, corresponding to other clinical definitions of the ILI (e.g., Centers for Disease Control and Prevention’s [CDC] definition [modified or not]).","definition_or_measurement_approach":"Laboratory confirmation by RT-PCR and/or RT-PCR + culture; uses alternative clinical ILI case definitions (e.g., CDC definitions); measured from 14 days after vaccination."}
• {"endpoint_text":"- Subtype of virus in laboratory-confirmed (RT-PCR-confirmed cases and in RT-PCR + culture-confirmed cases) influenza Type A cases, from 14 days after vaccination.","definition_or_measurement_approach":"Laboratory subtyping of influenza A (e.g., H1N1, H3N2) on RT-PCR or RT-PCR + culture-confirmed cases from 14 days post-vaccination."}
• {"endpoint_text":"- First occurrence of laboratory-confirmed (RT-PCR-confirmed cases and in RT-PCR + culture-confirmed cases) influenza symptomatic disease irrespective of strain/type, from 14 days after vaccination.","definition_or_measurement_approach":"Any laboratory-confirmed influenza (RT-PCR and/or culture) symptomatic disease from 14 days post-vaccination; lab confirmation methods specified."}
• {"endpoint_text":"- First occurrence of laboratory-confirmed (RT-PCR-confirmed cases and in RT-PCR + culture-confirmed cases) influenza Type B symptomatic disease, from 14 days after vaccination.","definition_or_measurement_approach":"RT-PCR and/or culture confirmation of influenza B symptomatic disease from 14 days after vaccination."}
• {"endpoint_text":"- First occurrence of any ILIs irrespective of causal agent (confirmed or not by laboratory [RT-PCR-confirmed cases and in RT-PCR + culture-confirmed cases]), from 14 days after vaccination.","definition_or_measurement_approach":"Clinical ILI episodes regardless of laboratory confirmation; includes RT-PCR and/or culture-confirmed as subset; measured from 14 days post-vaccination."}
• {"endpoint_text":"- Severity (mean and maximum grading of symptoms) and duration of ILI episodes, with a trapezoidal calculation of the area under the curve [AUC] of the daily scores on the Flu-PRO® questionnaire, by treatment group (OVX836 and placebo).","definition_or_measurement_approach":"Severity graded (mean and max) and duration assessed using daily Flu-PRO® questionnaire scores; trapezoidal AUC calculation by treatment arm."}
• {"endpoint_text":"- SF-12 HRQoL physical and mental components scores changes between baseline (Day 1) and 14 days after each ILI episode start date, by treatment group (OVX836 and placebo).","definition_or_measurement_approach":"Change from baseline of SF-12 physical and mental component scores measured at baseline and 14 days after ILI episode start, compared by treatment group."}
• {"endpoint_text":"- Mean and maximum EQ-5D-5L HRQoL scores and trapezoidal calculation of the AUC of the daily scores, by treatment group (OVX836 and placebo).","definition_or_measurement_approach":"EQ-5D-5L daily scores; mean and max scores and AUC (trapezoidal) calculated by treatment group."}
• {"endpoint_text":"- Mean and maximum EQ-5D-L HRQoL visual analog scale (VAS) score and trapezoidal calculation of the AUC of the daily scores, by treatment group (OVX836 and placebo).","definition_or_measurement_approach":"EQ-5D VAS daily scores; mean and max VAS and AUC (trapezoidal) by treatment group."}
• {"endpoint_text":"- Composite endpoint taking into account Flu-PRO® AUC, SF-12 change versus baseline and EQ-5D AUCs.","definition_or_measurement_approach":"Composite combining Flu-PRO® AUC, SF-12 change vs baseline and EQ-5D AUCs; method of combination described in protocol."}
• {"endpoint_text":"- Occurrence of solicited local and systemic signs and symptoms during 7 days after vaccine administration","definition_or_measurement_approach":"Solicited local and systemic reactogenicity signs/symptoms recorded during 7 days post-vaccination (daily eDiary/ePRO)."}
• {"endpoint_text":"- Occurrence of unsolicited AEs during 29 days after vaccine administration.","definition_or_measurement_approach":"Recording of unsolicited adverse events for 29 days post-vaccination."}
• {"endpoint_text":"- Occurrence of SAEs/AESI/NOCD/MAAEs during the whole study period.","definition_or_measurement_approach":"Serious adverse events, adverse events of special interest, new onset chronic disease and medically attended adverse events recorded throughout entire study duration."}
• {"endpoint_text":"- CMI response to OVX836 (480μg) in terms of NP-specific T-cell (number of spot-forming cells [SFC] per million PBMCs), measured by IFNγ ELISPOT, at Day 1 and Day 8, in a limited subset of 56 subjects (28 placebo and 28 OVX836 recipients).","definition_or_measurement_approach":"Cell-mediated immunity measured by IFNγ ELISPOT (NP-specific T-cell SFC per million PBMCs) at Day 1 and Day 8 in subset of 56 subjects."}
• {"endpoint_text":"- Percentage of NP specific CD4+ and CD8+ T-cell measured by flow cytometry on PBMCs as expressing cytokines, e.g. IFNγ, IL-2 and TNFα, at pre-injection baseline (Day 1) and at Day 8, in a limited subset of 56 subjects (28 placebo and 28 OVX836 recipients)","definition_or_measurement_approach":"Flow cytometry on PBMCs measuring percentage of NP-specific CD4+ and CD8+ T-cells expressing cytokines (IFNγ, IL-2, TNFα) at Day 1 and Day 8 in subset."}
• {"endpoint_text":"- Anti-NP IgG measured by Enzyme Linked Immunosorbent Assay (ELISA) at pre-injection baseline (Day 1) and at Day 8, in a limited subset of 56 subjects (28 placebo and 28 OVX836 recipients).","definition_or_measurement_approach":"Anti-NP IgG measured by ELISA at Day 1 and Day 8 in subset of 56 subjects."}
• {"endpoint_text":"- The analyses of the primary and secondary efficacy endpoints will be replicated irrespectively of the time between vaccination and cases occurrence","definition_or_measurement_approach":"Efficacy endpoint analyses will be replicated regardless of time elapsed between vaccination and case occurrence (analysis approach described in protocol)."}

Methods

• Invitation letters (country-specific invitation letters listed in recruitment documents)
• Flyers and posters (country/site-specific recruitment flyers and posters)
• Emails (recruitment emails to potential participants / site contact lists)
• Website content and website text for recruitment (site-specific recruitment web pages)
• Social media advertising/materials (social media recruitment assets listed)
• Pre-screening webform (online pre-screening questionnaire/webform)
• Site-based outreach via vaccination departments and trial centres (site contact details and department vaccination listed)
• Phone contact for follow-up and screening (Day 29 phone contact and other phone contact procedures)

Germany

Earliest CTIS Part Ii Submission Date

04-06-2025

Latest Decision Or Authorization Date

28-08-2025

Processing Time Days

85

Number Of Sites

1

Number Of Participants

200

Finland

Earliest CTIS Part Ii Submission Date

06-05-2025

Latest Decision Or Authorization Date

28-08-2025

Processing Time Days

114

Number Of Sites

9

Number Of Participants

1000

France

Earliest CTIS Part Ii Submission Date

03-03-2025

Latest Decision Or Authorization Date

28-08-2025

Processing Time Days

178

Number Of Sites

3

Number Of Participants

280

Belgium

Earliest CTIS Part Ii Submission Date

04-06-2025

Latest Decision Or Authorization Date

02-02-2026

Processing Time Days

243

Number Of Sites

4

Number Of Participants

1370

Primary sponsor

Full Name

Osivax

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Clinfidence B.V.

Responsibilities

Pharmacovigilance / SAE reporting (sponsorDuties code: 8); contact sae@clinfidence.com

Name

Clinchoice S.r.l.

Responsibilities

Multiple trial management responsibilities (sponsorDuties codes: 1,12,13,5); contact jenny.zecchini@clinchoice.com

Name

TrialPEX

Responsibilities

Management of patient reimbursement where applicable (sponsorDuties code: 15); contact a.hupe@trialpex.com

Name

Phlexglobal Limited

Responsibilities

eTMF provider (sponsorDuties code: 15); contact RCulleton@phlexglobal.com

Third parties

• {"country":"Netherlands","full_name":"Clinfidence B.V.","duties_or_roles":"sponsorDuties codes: [8]; contact: sae@clinfidence.com","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Cryoport France","duties_or_roles":"sponsorDuties code: [15]; value: Long term storage of samples and destruction; contact: contact@cell-and-co.com","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"OSIVAX Belgique","duties_or_roles":"sponsorDuties code: [4]; contact: fnicolas@osivax.com","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Vismederi S.r.l.","duties_or_roles":"sponsorDuties code: [4]; contact: info@vismederi.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"France","full_name":"Euromed Pharma France","duties_or_roles":"sponsorDuties code: [14]; contact: charlotte.juvernat@euromed-pharma.com","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"TrialPEX","duties_or_roles":"sponsorDuties code: [15]; value: Management of Patient reimbursement where applicable; contact: a.hupe@trialpex.com","organisation_type":"Industry"}
• {"country":"Italy","full_name":"Clinchoice S.r.l.","duties_or_roles":"sponsorDuties codes: [1,12,13,5]; contact: jenny.zecchini@clinchoice.com","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Insife","duties_or_roles":"sponsorDuties code: [15]; value: Safety DB provider; contact: hello@insife.com","organisation_type":"Industry"}
• {"country":"France","full_name":"Mapi Research Trust","duties_or_roles":"sponsorDuties code: [15]; value: Questionnaires provider; contact: Magdalena.Heluszka@mapi-trust.org","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Oriola Finland Oy","duties_or_roles":"sponsorDuties codes: [14,15]; value: Depot and Distributor of IMP in Finland; contact: clinical.services@oriola.com","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"KCAS Bio","duties_or_roles":"sponsorDuties code: [4]; contact: christine.bain@kcasbio.com","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"S-Clinica","duties_or_roles":"sponsorDuties codes: [15,3]; value: eDiary/ePRO provider; contact: info@s-clinica.com","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Inferential","duties_or_roles":"sponsorDuties codes: [10,6,7]; contact: contact@inferential.fr","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Phlexglobal Limited","duties_or_roles":"sponsorDuties code: [15]; value: eTMF provider; contact: RCulleton@phlexglobal.com","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Viedoc","duties_or_roles":"sponsorDuties code: [7]; contact: info@viedoc.biz","organisation_type":"Industry"}
• {"country":"Belgium","full_name":"CEVAC CORE LAB","duties_or_roles":"sponsorDuties code: [4]; contact: cevaclab@ugent.be","organisation_type":"Educational Institution"}