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

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