OVX033 for Coronavirus infection | Sarbecoviruses disease

Inclusion criteria

• {"criterion_text":"- Written informed consent\n- Healthy male or female subjects, as determined by medical history and medical examination.\n- Aged 18 to 49 years in Phase 1, 18 years and older in Phase 2a.\n- Subject beneficiary from a social security scheme.\n- All subjects should have been vaccinated with a licensed SARS-CoV-2 (COVID-19) vaccine (at least two immunizations). The last dose should have been injected at least one month before the administration of the investigational vaccine.\n- Subjects aged 65 years and over, or aged 80 years and over should be compliant with the current Haute Autorité de Santé (HAS) recommendations (May 2024): “Vaccination against COVID-19 is recommended each year in the fall for people aged 65 and over, respecting a period of at least 6 months since the last dose of vaccine against COVID-19 or the latest COVID-19 infection; this period is reduced to 3 months for people aged 80 and over”. The last dose should have been injected at least one month before the administration of the investigational vaccine.\n- Healthcare professionals and medical students should be compliant with the most updated version of the HAS recommendations which concern their specific status. The last dose should be a minimum of 1 month before administration of the investigational vaccine.\n- Reliable and willing to make themselves available for the duration of the study, willing and able to follow study procedures.\n- Able to use an eDiary on a tablet, smartphone, laptop, or personal computer."}

Exclusion criteria

• {"criterion_text":"- Subjects with a body mass index (BMI) <18 kg/m² or >30 kg/m² at inclusion.\n- Any known or suspected immunodeficient conditions.\n- Past or current history of significant autoimmune diseases, as judged by the Investigator.\n- Known or suspected infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).\n- Current history of medical illness such as diabetes, hypertension, heart, renal, or hepatic diseases, as judged by the Investigator.\n- Hereditary or acquired hemorrhagic tendency or coagulation dysfunction (e.g., cytokine defects, coagulation disorders, or platelet disorder), or history of serious bleeding, or history of massive bleeding after intramuscular injection, intravenous puncture, or ecchymosis.\n- History of receiving blood, blood components, or immunoglobulins within 3 months prior to inclusion, or planned to receive such product during the entire study period.\n- Presence of an acute febrile illness on the day of planned vaccination or within 72 hours prior to it (oral temperature ≥38.0°C; temporary exclusion criterion).\n- Past or current history of any progressive or severe neurological disorder, seizure disorder, or Guillain-Barré syndrome.\n- 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.\n- Subject with 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- 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- Subjects having presented medically significant adverse event after having received a SARS-CoV-2 licensed vaccine\n- Subjects currently treated with medications intended to prevent SARS-CoV-2 infection or disease (COVID-19) complications.\n- Prophylactic or therapeutic use of any anti(retro)virals by systemic route during the study. Topical application is allowed.\n- History of severe allergic reactions and/or anaphylaxis, or serious adverse reactions to vaccines, or allergy to kanamycin and/or any other component of the vaccine\n- Any contraindication to intramuscular administration, as judged by the Investigator.\n- Past (stopped less than 6 months before enrolment) or current smoking habit above 10 cigarettes per day.\n- Any known or suspected immunodeficient conditions.\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- Subjects having participated in the OVX033-001 study\n- Past (stopped less than 6 months before enrolment) or current history of alcohol consumption (more than 2 glasses per day, more than 10 glasses per week, or absence of any days within a week without consumption. A standard glass contains 10 g of alcohol corresponding to 10 cl of wine, 25 cl of beer at 5%, or 3 cl of alcohol at 40% [Société Française d’Alcoologie, 2023]).\n- Past (stopped less than 6 months before enrolment) or current history of use of recreational drugs.\n- Subjects weighing less than 50 kg at inclusion.\n- Past or current history of any progressive or severe neurological disorder, seizure disorder, or Guillain-Barré syndrome.\n- Subjects currently participating in another clinical trial\n- SARS-CoV-2 infection within the past 3 months prior to enrolment, RT-PCR-confirmed SARS-CoV-2 infection or ongoing symptom of COVID-19.\n- Subjects 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.\n- Planning to receive other vaccines between inclusion (Day 1) and Day 57 (28 days following the second IMP administration). All kinds of vaccinations will be authorized after Day 57."}

Primary endpoints

• {"endpoint_text":"- Phase 1 •\tNumber and percentage of subjects reporting solicited local and systemic symptoms during 7 days after each administration in each cohort/group.","definition_or_measurement_approach":"Solicited local and systemic symptoms collected for 7 days after each administration; reported as number and percentage of subjects."}
• {"endpoint_text":"- Pase 1 •\tNumber and percentage of doses followed by the reporting of solicited local and systemic symptoms during 7 days after each administration in each cohort/group.","definition_or_measurement_approach":"Solicited symptoms counted per dose for 7 days post-administration; reported as number and percentage of doses followed by solicited symptoms."}
• {"endpoint_text":"- Phase 1 •\tNumber and percentage of subjects reporting unsolicited AEs during 29 days after each administration in each cohort/group.","definition_or_measurement_approach":"Unsolicited adverse events collected for 29 days after each administration; reported as number and percentage of subjects."}
• {"endpoint_text":"- Phase 1 •\tNumber and percentage of doses followed by the reporting of unsolicited AEs during 29 days after each administration in each cohort/group.","definition_or_measurement_approach":"Unsolicited AEs counted per dose for 29 days post-administration; reported as number and percentage of doses."}
• {"endpoint_text":"- Phase 1 •\tNumber and percentage of subjects reporting COVID-19 symptoms and laboratory-confirmed SARS-CoV-2 and/or influenza cases during the entire study duration in each cohort/group.","definition_or_measurement_approach":"Clinical COVID-19 symptoms and laboratory-confirmed SARS‑CoV‑2 and/or influenza cases monitored during entire study; reported as number and percentage of subjects."}
• {"endpoint_text":"- Phase 1 •\tNumber and percentage of subjects reporting AESI during the entire study duration in each cohort/group.","definition_or_measurement_approach":"Adverse events of special interest (AESI) recorded during entire study; reported as number and percentage of subjects."}
• {"endpoint_text":"- Phase 1 •\tNumber and percentage of subjects reporting MAAEs during the entire study duration in each cohort/group.","definition_or_measurement_approach":"Medically attended adverse events (MAAEs) recorded during entire study; reported as number and percentage of subjects."}
• {"endpoint_text":"- Phase 1 •\tNumber and percentage of subjects reporting SAEs during the entire study duration in each cohort/group.","definition_or_measurement_approach":"Serious adverse events (SAEs) recorded during entire study; reported as number and percentage of subjects."}
• {"endpoint_text":"- Phase 2a •\tSame reactogenicity and safety endpoints as in Phase 1.","definition_or_measurement_approach":"Same safety and reactogenicity measures as Phase 1 (solicited symptoms 7 days, unsolicited AEs 29 days, AESI, MAAEs, SAEs during study)."}
• {"endpoint_text":"- Phase 2a •\tCell-mediated immune response to OVX033 after 1st and 2nd administrations at three dose levels (100µg, 250µg and 500µg) in terms of change of NP-specific SFUs per million PBMCs, measured by IFNγ ELISPOT, at Day 8/Day 36/Day 57 versus pre-1st injection baseline (Day 1) or/and pre-2nd injection (Day 29) in each cohort/group.","definition_or_measurement_approach":"NP-specific spot-forming units (SFUs) per million PBMCs measured by IFNγ ELISPOT at Day 8, Day 36, Day 57; comparisons versus baseline (Day 1) and/or pre-2nd injection (Day 29)."}

Secondary endpoints

• {"endpoint_text":"- Phase 1 •\tCell-mediated immune response to OVX033 after 1st and 2nd administrations at three dose levels (100µg, 250µg and 500µg) in terms of change of NP-specific SFUs per million PBMCs, measured by IFNγ ELISPOT, at Day 8/Day 36/Day 57 versus pre-1st injection baseline (Day 1) or/and pre-2nd injection (Day 29) in each cohort/group.","definition_or_measurement_approach":"IFNγ ELISPOT NP-specific SFUs per million PBMCs at Day 8/36/57 versus baseline/timepoints as stated."}
• {"endpoint_text":"- Phase 1 •\tNP-specific CD4+ and CD8+T-cell frequencies measured by flow cytometry (on PBMCs) as expressing IL-2, TNFα and/or IFNγ upon in vitro stimulation at Day 8/Day 36/Day 57 versus pre-1st injection baseline (Day 1) or/and pre-2nd injection (Day 29) in a subset or in all subjects depending on the response measured in the ELISPOT assay.","definition_or_measurement_approach":"Flow cytometry (PBMCs) measuring frequencies of NP-specific CD4+ and CD8+ T‑cells expressing IL‑2, TNFα and/or IFNγ at Day 8/36/57 versus baseline/timepoints."}
• {"endpoint_text":"- Phase 1 •\tGeometric mean titers (GMTs) of anti-nucleocapsid (N) Immunoglobulin G (IgG) (ELISA, serum) at Day 29/Day 57 versus pre-1st injection baseline (Day 1) or/and pre-2nd injection (Day 29) in each cohort/group.","definition_or_measurement_approach":"Anti-N IgG GMTs measured by ELISA in serum at Day 29 and Day 57 versus baseline/timepoints."}
• {"endpoint_text":"- Phase 1 •\tNumber and percentage of subjects with an increase (two-fold or four-fold) in anti-N IgG (ELISA, serum) titer at Day 29/Day 57 versus pre-1st injection baseline (Day 1) or/and pre-2nd injection (Day 29) in each cohort/group.","definition_or_measurement_approach":"Proportion of subjects with ≥2-fold or ≥4-fold increase in anti-N IgG titers (ELISA) at Day 29/57 vs baseline/timepoints."}
• {"endpoint_text":"- Phase 1 •\tPersistence of the cell-mediated and humoral immune responses to OVX033 at Month 6 (5 months after the 2nd administration). The CMI response at Day 180 will be assessed in all subjects using IFNγ ELISPOT. The percentage of CD4+ and CD8+ T-cells will be evaluated using intracellular staining (ICS), in a subset or in all subjects depending on the response measured in the ELISPOT assay.","definition_or_measurement_approach":"Assessment at Month 6 (Day 180) using IFNγ ELISPOT for CMI; ICS for CD4+/CD8+ T‑cell percentages in subset or all subjects."}
• {"endpoint_text":"- Phase 1 •\tGeometric mean titers (GMTs) of anti-OVX313 IgG (ELISA, serum) at Day 29/Day 57 versus pre-1st injection baseline (Day 1) or pre-2nd injection (Day 29) in each cohort/group.","definition_or_measurement_approach":"Anti-OVX313 IgG GMTs measured by ELISA at Day 29/57 versus baseline/timepoints."}
• {"endpoint_text":"- Phase 1 •\tAnti-C4bp (C4b-binding protein) oligomerization domain IgG level (ELISA, serum) in subjects presenting a significant increase in the anti-OVX313 IgG.","definition_or_measurement_approach":"Anti-C4bp oligomerization domain IgG levels measured by ELISA in subjects with significant anti-OVX313 IgG increase."}
• {"endpoint_text":"- Phase 2a •\tSame as secondary endpoints/estimands of Phase 1 (except ELISPOT response which is a primary endpoint/estimand in Phase 2a).","definition_or_measurement_approach":"Phase 2a secondary endpoints align with Phase 1 secondary endpoints; ELISPOT is primary in Phase 2a."}

France

Earliest CTIS Part Ii Submission Date

08-01-2025

Latest Decision Or Authorization Date

24-01-2025

Processing Time Days

16

Number Of Sites

1

Number Of Participants

240

Primary sponsor

Full Name

Osivax

Organisation Type

Pharmaceutical company

Country Of Registered Address

France