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 18-59 years

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Osivax

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

8 Sep 2025 → 18 May 2026

Decision date (initial)

2025-06-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Osivax

External identifiers

EU CT number

2024-520354-37-00

WHO UTN

U1111-1306-4481

ClinicalTrials.gov

NCT05569239

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy

To evaluate the efficacy following a vaccination with OVX836 influenza vaccine (480μg) in preventing RT-PCR-confirmed influenza Type A clinical disease (protocol-defined ILI), in comparison to placebo.

Secondary objectives 11

1. To evaluate the efficacy following a vaccination with OVX836 influenza vaccine (480μg) in preventing laboratory-confirmed influenza Type A clinical disease, using other definitions of the ILI, in comparison to placebo.
2. To evaluate the efficacy following a vaccination with OVX836 influenza vaccine (480μg) in preventing laboratory-confirmed influenza clinical disease by subtypes of influenza Type A (H1N1, H3N2…), in comparison to placebo.
3. To evaluate the efficacy following a vaccination with OVX836 influenza vaccine (480μg) in preventing laboratory-confirmed influenza clinical disease irrespective of influenza strain, in comparison to placebo.
4. To evaluate the efficacy following a vaccination with OVX836 influenza vaccine (480μg) in preventing laboratory-confirmed influenza Type B clinical disease, in comparison to placebo
5. To evaluate the efficacy following a vaccination with OVX836 influenza vaccine (480μg) in preventing laboratory-confirmed influenza Type A clinical disease (protocol-defined ILI), in comparison to placebo, at the peak of influenza (determined on the basis of national epidemiological sources as defined by the Adjudication Committee [AC]).
6. To evaluate, for each of the case definitions and observation periods under evaluation, the severity and duration of clinical influenza disease with OVX836 influenza vaccine (480μg) in comparison to placebo.
7. To evaluate, for each of the case definitions and observation periods under evaluation, the impact of the disease on the health-related quality of life (HRQoL) with OVX836 influenza vaccine (480μg) in comparison to placebo.
8. To combine and evaluate a composite endpoint taking into account the severity and duration of clinical influenza disease, and the impact on the HRQoL with OVX836 influenza vaccine (480μg) in comparison to placebo.
9. To evaluate the efficacy following a vaccination with OVX836 influenza vaccine (480μg) in preventing clinical influenza-like disease irrespective of causal infectious agent, in comparison to placebo.
10. To evaluate the safety and reactogenicity of one dose of OVX836 influenza vaccine (480μg), in comparison to placebo
11. To evaluate the cell-mediated immune (CMI) and humoral responses to one dose of OVX836 influenza vaccine (480μg), in comparison to placebo in a subset of subjects.

Conditions and MedDRA coding

Influenza disease

Study design 5 periods

Regulatory references

Scientific advice from competent authorities

Ema Healthcare Limited, Federal Agency For Medicines And Health Products

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Written informed consent
2. Healthy male or female subjects, as determined by medical history and medical examination.
3. Between the ages of 18 and 59 years, inclusive
4. Subjects compliant with the reproductive criteria for male and female participants
5. Reliable and willing to make themselves available for the duration of the study, and willing and able to follow study procedures
6. Able to read, understand, and complete an eDiary and electronic patient-reported outcome (ePRO)
7. 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.
8. Able to read and sign the subject information sheet and informed consent form (ICF).

Exclusion criteria 30

1. 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
2. Prophylactic or therapeutic use of influenza antivirals within 7 days prior to the day of study vaccination or during the whole study duration.
3. 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
4. Females planning to become pregnant or planning to discontinue contraceptive precautions until the end of the trial
5. Any contraindication to intramuscular administration, as judged by the Investigator
6. Presence of extended tattoos on both deltoid muscles
7. 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
8. Any known or suspected immunodeficient conditions
9. 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
10. Past or current history of significant autoimmune diseases, as judged by the Investigator
11. Known or suspected infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
12. Any medical illness such as diabetes, hypertension, heart, renal, or hepatic diseases, as judged by the Investigator
13. Planned absences without access to the investigational site, i.e. vacation or business trips, for more than 7 consecutive days during the study period
14. Pregnant or lactating woman
15. 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
16. Planning to receive any other vaccines during the first 28 days following the study vaccine administration, except COVID-19 vaccines which can be administered from 14 days following the study vaccine administration
17. Administration of any investigational or non-registered drug or vaccine within 1 month prior to the administration of study vaccines, or planned administration of any such product during the whole study period
18. 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.
19. Presence of an acute febrile illness on the day of planned vaccination (oral temperature ≥37.5°C; temporary exclusion criterion).
20. Diagnosed long COVID-19 subjects
21. 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
22. 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
23. Having participated or currently participating in an OVX836 study, except the current OVX836-005 study, or in the OVX-FLU-002 study
24. 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
25. Past (stopped less than 6 months before enrolment) or current smoking habit above 10 cigarettes per day.
26. 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.
27. Past (stopped less than 6 months before enrolment) or current use of recreational drugs, which could interfere with the adherence to the protocol procedures
28. 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
29. 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
30. Current or past history of progressive or severe uncontrolled neurological disorder, or current or past history of seizure disorder or Guillain-Barré syndrome

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 17

1. 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]).
2. 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.
3. 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.
4. 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.
5. 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.
6. 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).
7. 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).
8. Mean and maximum EQ-5D-5L HRQoL scores and trapezoidal calculation of the AUC of the daily scores, by treatment group (OVX836 and placebo).
9. 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).
10. Composite endpoint taking into account Flu-PRO® AUC, SF-12 change versus baseline and EQ-5D AUCs.
11. Occurrence of solicited local and systemic signs and symptoms during 7 days after vaccine administration
12. Occurrence of unsolicited AEs during 29 days after vaccine administration.
13. Occurrence of SAEs/AESI/NOCD/MAAEs during the whole study period.
14. 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).
15. 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)
16. 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).
17. The analyses of the primary and secondary efficacy endpoints will be replicated irrespectively of the time between vaccination and cases occurrence

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Osivax

Sponsor organisation

Osivax

Address

70 Rue Saint Jean De Dieu

City

Lyon

Postcode

69007

Country

France

Scientific contact point

Organisation

Osivax

Contact name

Linda Lebon

Public contact point

Organisation

Osivax

Contact name

Linda Lebon

Third parties 16

Locations

4 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 130 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications