Clinical trial NCT06255626: Safety and Immunogenicity of a Sub-unit Protein CD40.RBDv Bivalent COVID-19 Vaccine, Adjuvanted or Not, as a Booster in Volunteers.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: COVID-19
Keywords: Vaccine
COVID-19
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Vaccine Research Institute (VRI), France
name: EnnoDc (previously known as LinKinVax)
First posted: 2024-02-13
Enrollment: 215
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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

Detailed description: 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)

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of participants without any grade 3 or 4 biological or clinical solicited local/systemic or unsolicited AEs between D1 and Month 3 after each IMP/vaccine administration and considered to be related or possibly related to IMP administration
timeFrame: Month 3
measure: Neutralization antibodies titers (anti-RBD) against the original strain D614G and the relevant strain circulating at time of the study Month 1
timeFrame: Month 1
Secondary outcomes:
measure: Number of volunteers with solicited local and systemic Adverse Reactions (ARs)
timeFrame: Day 8
measure: Number of volunteers with Adverse Events (AEs) other than solicited adverse events
timeFrame: Day 1 to Months 3 after each dose
measure: Number of volunteers with Serious Adverse Events (SAEs), grade 3 and grade 4
timeFrame: Day 1 to Months 3 after each dose
measure: Number of volunteers with events leading to discontinuation of the vaccine regimen
timeFrame: Through study completion, an average of 15 months
measure: Seroconversion rate defined by an increase of 4 folds between day1 (baseline before vaccination) and Month 1 in anti-RBD IgG binding titers
timeFrame: Month 1
measure: To assess the cross-neutralization against the most relevant VOCs at the time of the study
timeFrame: Day 1 (before each vaccination) day 8, day 14 and M1 after each vaccination, M3, M6, M12 (ie. 12 months after 1st dose and 9 months after 2nd dose) and M15 (ie. 15 months after 1st dose and 12 months after 2nd dose)
measure: To analyze the correlation between the magnitude of CD4+ specific T cell responses and levels of IgG specific responses
timeFrame: Day 1 (before each vaccination) day 14 after each vaccination, M3, M6, M12 (ie. 12 months after 1st dose and 9 months after 2nd dose) and M15 (ie. 15 months after 1st dose and 12 months after 2nd dose)
measure: To characterize the vaccine efficacy by evaluating the number of COVID-19 infections (PCR+) and severity (based on CDC definition) in participants throughout the study follow-up.
timeFrame: Through study completion, an average of 15 months
measure: To evaluate the Cytokine expression patterns of CD4 and CD8 T cells as measured by intracellular cytokine staining assay
timeFrame: Day 1 (before each vaccination) day 14 after each vaccination, M3, M6, M12 (ie. 12 months after 1st dose and 9 months after 2nd dose) and M15 (ie. 15 months after 1st dose and 12 months after 2nd dose)
measure: Percentages of T cells producing at least one cytokine after in vitro stimulation
timeFrame: Through study completion, an average of 15 months
measure: Concentration (pg/mL) of cytokines produced by stimulated PBMC
timeFrame: Through study completion, an average of 15 months
Other outcomes:
Locations:
city: Créteil
country: France
facility: Hopital Henri Mondor
city: Paris
country: France
facility: Hôpital Cochin
Study officials:
References: