Safety and Immunogenicity of a Sub-unit Protein CD40.RBDv Bivalent COVID-19 Vaccine, Adjuvanted or Not, as a Booster in Volunteers.

A Phase 1/2 Multicenter, Randomized Study of the Safety and Immunogenicity of a Sub-unit Protein CD40.RBDv Bivalent COVID-19 Vaccine, Adjuvanted or Not, as a Booster in Volunteers.

The goal of this clinical trial, on healthy volunteers, is to learn more about safety and reactogenicity of the CD40.RBDv vaccine.

The main questions that will be studied are :

• Is the CD40.RBDv (adjuvanted or not) safe ?
• Does the CD40.RBDv (adjuvanted or not) imply an immunologic response ? Participants will receive, depending on their randomization arm, 1 or 2 injections of the CD40.RBDv vaccine or a single injection of approved mRNA vaccine

Phase 1/2a randomized, multicentre trial with four cohorts of two arms in two parts.

Part 1:

Cohort 1: Low dose (LD) CD40.RBDv vaccine non adjuvanted or mRNA vaccine (5:1 ratio)

Cohort 2: LD CD40.RBDv vaccine adjuvanted or mRNA vaccine (5:1 ratio)

Cohort 3: High dose (HD) CD40.RBDv vaccine non adjuvanted or mRNA vaccine (5:1 ratio)

Cohort 4: SC injection of HD CD40.RBDv vaccine adjuvanted or mRNA vaccine (5:1 ratio)

A substancial amendment (January 2025) has removed the randomisation to mRNA vaccine from the study design

Go-criterion for opening enrolment within cohorts are detailed into the protocol.

Part 2 at Month 3 :

Group 1: Volunteers who received mRNA vaccine in Part 1 will not receive any vaccine

Group 2: Volunteers who received a first dose of CD40.RBDv vaccine (adjuvanted or not) in Part 1 but randomized (1:1) to receive no further dose of vaccine in Part 2.

Group 3: Volunteers who received a first dose of CD40.RBDv vaccine (adjuvanted or not) in Part 1 and randomized (1:1) to receive an additional dose of CD40.RBDv vaccine (adjuvanted or not)

Inclusion Criteria:

• Healthy volunteers Age ≥18 and <85
• Able to understand and comply with planned study procedures and sign an informed consent before performance of any study-related screening procedures
• Who has received a primary series of vaccination and ≥ 1 booster(s) of COVID-19 mRNA vaccination(s) with the last boost at least 6 months prior to the inclusion in the study
• Subjects has adequate organ functions, evidenced by normal ALT, AST, and alkaline phosphatase
• Normal haematology lab values
• Negative virology assessment
• Normal Urine testing
• Volunteers must meet the eligibility criteria in the approved package labelling of the active comparator
• For women of childbearing potential: use of an effective contraceptive method and negative pregnancy test. For male participants, use of an effective method of contraception with their partner

Exclusion Criteria:

• Acute febrile infection within the previous 72 hours and/or presenting symptoms suggestive of COVID-19 or SARS CoV 2 infection within the previous 28 days
• Immunosuppressive medications received within last three months before first IMP administration or within 6 months for chemotherapies
• Immunoglobulins within 90 days before first IMP administration
• Blood products within 120 days before first IMP administration
• Any medical condition, such as cancer, that might impair the immune response
• Use of any experimental therapy
• Intent to participate in another study of an investigational research agent within 4 weeks prior to the enrolment visit or until the end of the study
• Currently pregnant or breastfeeding
• History of severe adverse events following vaccine administration
• Any bleeding disorder considered as a contraindication to an intramuscular injection
• A condition that requires active medical intervention or monitoring to avert grave danger to Asthma other than mild, well-controlled asthma.
• Hypertension
• BMI ≥ 40 kg/m2; ≤ 18 kg/m2; or BMI ≥ 35 kg/m2 with 2 or more of the following: age > 45, current smoker, known hyperlipidemia, blood pressure is defined as consistently ≥ 140 mm Hg systolic and ≥ 90 mm Hg diastolic
• Malignancy
• Asplenia
• Seizure disorder
• History of hereditary angioedema acquired angioedema, or idiopathic angioedema
• History of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, clinically significant arrhythmia (including arrhythmia requiring medication, treatment, or clinical follow-up
• History of autoimmune disease
• Any medical, occupational, or other condition that, in the judgment of the investigator, would interfere with or serve as a contraindication to protocol adherence
• Psychiatric condition that precludes compliance with the protocol.
• Live attenuated vaccines received within 30 days before first IMP administration or scheduled within 28 days after one of the last injection according to the protocol
• Vaccines that are not live attenuated vaccines and were received within 21 days prior to first IMP administration
• Allergy treatment with antigen injections within 30 days before first IMP administration and until the end of the study