Phase 1 (sequential)/2a (parallel), double-blind, multicenter, randomized, controlled study to evaluate the safety and immunogenicity of two administrations of OVX033 sarbecovirus candidate vaccine, given intramuscularly (IM) at one-month interval, at three dose levels, in comparison to placebo, in subjects aged 18 years and older

2024-517396-20-00 Protocol OVX033-002 Phase I and Phase II (Integrated) - Other Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 1 sites · Protocol OVX033-002

Overview

Sponsor-declared trial summary

Phase Phase I and Phase II (Integrated) - Other
Status Authorised, recruitment pending
Participants planned 240
Countries 1
Sites 1

Sarbecoviruses disease

Phase 1 To evaluate the safety and reactogenicity of two IM administrations (one month apart) of OVX033 sarbecovirus candidate vaccine at three dose levels (100µg, 250µg and 500µg), in comparison to placebo, in subjects aged 18 to 49 years. Phase 2a • To evaluate the cell-mediated immunogenicity (NP-specific SFUs per …

Key facts

Sponsor
Osivax
Participant type
Healthy volunteers
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Virus Diseases [C02]
Decision date (initial)
2025-01-24
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Osivax

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Phase 1
To evaluate the safety and reactogenicity of two IM administrations (one month apart) of OVX033 sarbecovirus candidate vaccine at three dose levels (100µg, 250µg and 500µg), in comparison to placebo, in subjects aged 18 to 49 years.

Phase 2a
• To evaluate the cell-mediated immunogenicity (NP-specific SFUs per million PBMCs, measured by IFNγ ELISPOT) of two IM administrations (one month apart) of OVX033 sarbecovirus candidate vaccine at three dose levels (100µg, 250µg and 500µg), in comparison to placebo, in subjects aged 18 years and older.
• To evaluate the safety and reactogenicity of two IM administrations (one month apart) of OVX033 sarbecovirus candidate vaccine at three dose levels (100µg, 250µg and 500µg), in comparison to placebo, in subjects aged 18 years and older.

Secondary objectives 2

  1. Phase 1 • To evaluate the cell-mediated immunogenicity of two IM administrations (one month apart) of OVX033 sarbecovirus candidate vaccine at three dose levels (100µg, 250µg and 500µg), in comparison to placebo, in subjects aged 18 to 49 years. • To evaluate the humoral immunogenicity of two IM administrations (one month apart) of OVX033 sarbecovirus candidate vaccine at three dose levels (100µg, 250µg and 500µg), in comparison to placebo, in subjects aged 18 to 49 years.
  2. Phase 2a • To evaluate the humoral immunogenicity of two IM administrations (one month apart) of OVX033 sarbecovirus candidate vaccine at three dose levels (100µg, 250µg and 500µg), in comparison to placebo, in subjects aged 18 years and older. • To evaluate additional cell-mediated immunogenicity parameters (e.g., percentage of CD4+ and CD8+ T-cells expressing cytokines among IFNγ, IL2 and TNFα) of two IM administrations (one month apart) of OVX033 sarbecovirus candidate vaccine at three dose levels (100µg, 250µg and 500µg), in comparison to placebo, in subjects aged 18 years and older (in a subset or in all subjects depending on the ELISPOT results).

Conditions and MedDRA coding

Sarbecoviruses disease

VersionLevelCodeTermSystem organ class
23.0 PT 10051905 Coronavirus infection 100000004862

Study design 2 periods

#TitleAllocationBlindingRoles blindedArms
1 Phase 1
Phase 1 subjects will be healthy men and women aged 18 to 49 years. Three cohorts of 10 subjects (Total N=30) will be enrolled sequentially in a staggered manner (at an interval of 14 days) under the control of an independent Data Safety Monitoring Board (DSMB) (see flow chart of Phase 1): • Cohort 1 (N=10): 8 subjects receiving OVX033 100µg and 2 subjects receiving placebo (0.2 mL), two IM administrations on Day 1 and Day 29, in the deltoid of the non-dominant arm. • Approximately 14 days after the second administration in Cohort 1, the DSMB will assess the reactogenicity and safety of the vaccine and will (if applicable) authorize the second administration in Cohort 2. • Cohort 2 (N=10): 8 subjects receiving OVX033 250µg and 2 subjects receiving placebo (0.5 mL), two IM administrations on Day 1 and Day 29, in the deltoid of the non-dominant arm. • Approximately 14 days after the second administration in Cohort 2, the DSMB will assess the reactogenicity and safety of the vaccine in a cumulative manner and will (if applicable) authorize the second administration in Cohort 3. • Cohort 3 (N=10): 8 subjects receiving OVX033 500µg and 2 subjects receiving placebo (1.0 mL), two IM administrations on Day 1 and Day 29, in the deltoid of the non-dominant arm. • Approximately 14 days after the second administration in Cohort 3, the DSMB will assess the reactogenicity and safety of the vaccine in a cumulative manner, and will (if applicable) authorize the start of enrolment in Phase 2a.
 Randomised Controlled Double [{"id":99903,"code":1,"name":"Subject"},{"id":99902,"code":2,"name":"Investigator"}] Cohort 1: 8 subjects receiving OVX033 100µg and 2 subjects receiving placebo (0.2 mL), two IM administrations on Day 1 and Day 29, in the deltoid of the non-dominant arm
Cohort 2: 8 subjects receiving OVX033 250µg and 2 subjects receiving placebo (0.5 mL), two IM administrations on Day 1 and Day 29, in the deltoid of the non-dominant arm
Cohort 3: 8 subjects receiving OVX033 500µg and 2 subjects receiving placebo (1.0 mL), two IM administrations on Day 1 and Day 29, in the deltoid of the non-dominant arm.
2 Phase 2a
Phase 2a subjects will be healthy men and women aged 18 years and older. A total number of 210 subjects will be randomized (2:2:2:1) into four parallel treatment groups receiving two IM administrations, one month apart (Day 1 and Day 29): • Group 1: OVX033 100µg (0.2 mL) (N=60) • Group 2: OVX033 250µg (0.5 mL) (N=60) • Group 3: OVX033 500µg (1.0 mL) (N=60) • Group 4: Placebo (1.0 mL) (N=30).
 Randomised Controlled Double [{"id":99905,"code":2,"name":"Investigator"},{"id":99906,"code":1,"name":"Subject"}] Group 1: OVX033 100µg (0.2 mL) (N=60)
Group 2: OVX033 250µg (0.5 mL) (N=60)
Group 3: OVX033 500µg (1.0 mL) (N=60)
Group 4: Group 4: Placebo (1.0 mL) (N=30)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

  1. Written informed consent
  2. Healthy male or female subjects, as determined by medical history and medical examination.
  3. Aged 18 to 49 years in Phase 1, 18 years and older in Phase 2a.
  4. Subject beneficiary from a social security scheme.
  5. 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.
  6. 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.
  7. 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.
  8. Reliable and willing to make themselves available for the duration of the study, willing and able to follow study procedures.
  9. Able to use an eDiary on a tablet, smartphone, laptop, or personal computer.

Exclusion criteria 29

  1. Subjects with a body mass index (BMI) <18 kg/m² or >30 kg/m² at inclusion.
  2. Any known or suspected immunodeficient conditions.
  3. Past or current history of significant autoimmune diseases, as judged by the Investigator.
  4. Known or suspected infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
  5. Current history of medical illness such as diabetes, hypertension, heart, renal, or hepatic diseases, as judged by the Investigator.
  6. 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.
  7. 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.
  8. 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).
  9. Past or current history of any progressive or severe neurological disorder, seizure disorder, or Guillain-Barré syndrome.
  10. 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.
  11. Past (stopped less than 6 months before enrolment) or current smoking habit above 10 cigarettes per day.
  12. Subjects weighing less than 50 kg at inclusion.
  13. 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]).
  14. Past (stopped less than 6 months before enrolment) or current history of use of recreational drugs.
  15. Subjects having participated in the OVX033-001 study
  16. Prophylactic or therapeutic use of any anti(retro)virals by systemic route during the study. Topical application is allowed.
  17. 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
  18. Any contraindication to intramuscular administration, as judged by the Investigator.
  19. Subject with tattoos on both deltoid muscles.
  20. 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.
  21. 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
  22. Subjects having presented medically significant adverse event after having received a SARS-CoV-2 licensed vaccine
  23. Subjects currently treated with medications intended to prevent SARS-CoV-2 infection or disease (COVID-19) complications.
  24. 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.
  25. 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.
  26. 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.
  27. Female subjects: pregnant, wishing to be pregnant during the course of the study, breast-feeding or of childbearing potential without appropriate contraceptive methods in place for at least 2 months before enrolment, or with positive urine pregnancy test at Day 1 (or at Day 29 for the 2nd IMP administration). Appropriate contraceptive methods are to be maintained until the end of the trial (see Appendix A).
  28. Subjects receiving 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 3 months before study entry) chronic or prolonged (>10 days) use of systemic non-steroidal anti-inflammatory drugs, interferon, immunomodulators, allergy shots, as judged by the Investigator.
  29. Subjects currently participating in another clinical trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 10

  1. Phase 1 • Number and percentage of subjects reporting solicited local and systemic symptoms during 7 days after each administration in each cohort/group.
  2. Pase 1 • Number and percentage of doses followed by the reporting of solicited local and systemic symptoms during 7 days after each administration in each cohort/group.
  3. Phase 1 • Number and percentage of subjects reporting unsolicited AEs during 29 days after each administration in each cohort/group.
  4. Phase 1 • Number and percentage of doses followed by the reporting of unsolicited AEs during 29 days after each administration in each cohort/group.
  5. Phase 1 • Number 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.
  6. Phase 1 • Number and percentage of subjects reporting AESI during the entire study duration in each cohort/group.
  7. Phase 1 • Number and percentage of subjects reporting MAAEs during the entire study duration in each cohort/group.
  8. Phase 1 • Number and percentage of subjects reporting SAEs during the entire study duration in each cohort/group.
  9. Phase 2a • Same reactogenicity and safety endpoints as in Phase 1.
  10. Phase 2a • Cell-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.

Secondary endpoints 8

  1. Phase 1 • Cell-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.
  2. Phase 1 • NP-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.
  3. Phase 1 • Geometric 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.
  4. Phase 1 • Number 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.
  5. Phase 1 • Persistence 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.
  6. Phase 1 • Geometric 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.
  7. Phase 1 • Anti-C4bp (C4b-binding protein) oligomerization domain IgG level (ELISA, serum) in subjects presenting a significant increase in the anti-OVX313 IgG.
  8. Phase 2a • Same as secondary endpoints/estimands of Phase 1 (except ELISPOT response which is a primary endpoint/estimand in Phase 2a).

Investigational products

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

Test 1

OVX033

PRD10601740 · Product

Active substance
OVX033
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAMUSCULAR INJECTION
Authorisation status
Not Authorised
MA holder
OSIVAX
Paediatric formulation
No
Orphan designation
No

Placebo 1

CHLORURE DE SODIUM 0,9 % B. BRAUN, solution pour perfusion

PRD8723504 · Product

Active substance
Sodium Chloride
Substance synonyms
SODIUM CHLORID
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INJECTION
Authorisation status
Authorised
ATC code
B05XA03 — SODIUM CHLORIDE
Marketing authorisation
34009 360 487 9 9
MA holder
B.BRAUN MEDICAL SAS
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Osivax

3 Total trials 2 Ended
Commercial
Sponsor organisation
Osivax
Address
70 Rue Saint Jean De Dieu
City
Lyon
Postcode
69007
Country
France

Scientific contact point

Organisation
Osivax
Contact name
Florence Nicolas - Chief Development Officer

Public contact point

Organisation
Osivax
Contact name
Florence Nicolas - Chief Development Officer

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Authorised, recruitment pending 240 1
Rest of world — 0 —

Investigational sites

France

1 site · Authorised, recruitment pending
Assistance Publique Hopitaux De Paris
Centre d'Investigation Clinique Cochin-Pasteur -CIC1417, 27 Rue Du Faubourg Saint Jacques, 75014, Paris

Results and documents

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

Documents 16 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol_2024-517396-20-00 2.0
Protocol (for publication) D1_Protocol_2024-517396-20-00_Summary of changes 1.0
Protocol (for publication) D1_Protocol_2024-517396-20-00_Track changes 2.0 vs 1.0
Protocol (for publication) D4_Patient facing documents_Participant Diary 1.0
Recruitment arrangements (for publication) K1_Recruitment arrangements_FR 1.0
Recruitment arrangements (for publication) K2_Recruitment material_Poster 2.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Detenteurs autorite parentale 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Femme enceinte 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Participant 2.0
Subject information and informed consent form (for publication) L2_Other subject information material_Emergency card 1.0
Subject information and informed consent form (for publication) L2_Other subject information material_GP letter 1.0
Subject information and informed consent form (for publication) L2_Other subject information material_Study booklet 1.0
Subject information and informed consent form (for publication) L2_Other subject information material_Viedocme manual 1.0
Synopsis of the protocol (for publication) D1_Protocol synopsis FR_2024-517396-20-00 2.0
Synopsis of the protocol (for publication) D1_Protocol synopsis FR_2024-517396-20-00_Summary of changes 1.0
Synopsis of the protocol (for publication) D1_Protocol synopsis FR_2024-517396-20-00_Track changes 2.0 vs 1.0

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-15 France Acceptable
2025-01-15
 2025-01-24