Healthy Adults
Conditions
Keywords
COVID19 vaccine, phase 1, experimental medicine trial
Brief summary
The SOLVE-01 trial is a study evaluating four SARS-CoV-2 vaccines as booster injections: two experimental vaccines (CD40.RBDv and CD40.Pan.CoV, both combined with the Hiltonol® adjuvant) and two authorised vaccines (Comirnaty® and NuvaxovidTM). This trial is designed for healthy adults aged 18 to 65 at the time of signing the informed consent form. The main objectives of this trial are: * to evaluate the safety of the two experimental vaccines, * to determine the antibody response induced by the vaccines and its durability. Participants will: * Receive one injection of vaccine and two intradermal skin tests * Come to the hospital 10 visits for medical exams and blood and saliva sample collection * Keep a diary of their symptoms and the treatments taken
Interventions
BIOLOGICALCD40.RBDv vaccine adjuvanted with Hiltonol®
used at the dose of 1.0 mg subcutaneously Poly-ICLC adjuvant (Hiltonol) used at a dose of 1.0 mg and will be mixed with CD40.RBDv vaccine just prior to subcutaneous injection at day 0.
BIOLOGICALCD40.Pan.CoV vaccine adjuvanted with Hiltonol®
used at the dose of 1.0 mg subcutaneously Poly-ICLC adjuvant (Hiltonol) used at a dose of 1.0 mg and will be mixed with CD40.Pan.CoV vaccine just prior to subcutaneous injection at day 0.
BIOLOGICALComirnaty® vaccine
administered intramuscularly at day 0. The version of the Comirnaty® vaccine and the dose will be the one adapted to the variant circulating at the start of trial and authorised by EMA.
BIOLOGICALNuvaxovid™ vaccine
administered intramuscularly at day 0. The version of the Nuvaxovid™ vaccine and the dose will be the one commercialised at the start of trial and authorised by EMA.
Sponsors
ANRS, Emerging Infectious Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male and female subjects aged 18 to 65 years inclusive at the time of the screening visit 2. Having received at least two doses of COVID-19 mRNA vaccines in the past with the last dose received more than 6 months prior to IMP administration in the trial 3. In healthy condition or with stable health status which is defined as an existing disease that has not required a significant change in treatment or hospitalization for worsening before enrolment, and for which neither a significant change in treatment or hospitalization for worsening is expected in the near future. 4. For woman of childbearing potential: a negative Beta-HCG blood test measure during the screening visit, and a negative highly sensitive pregnancy urinary test the day of the vaccination visit * if heterosexually active female, consistently using a highly effective method of contraception with partner from at least 21 days prior to enrolment through 4 months after the IMP administration. Highly effective contraception is defined as using any of the following methods: * Combined hormonal contraception with inhibition of ovulation (estrogen and progesterone containing); * Intrauterine device (IUD); * Intrauterine hormone releasing system (IUS); * Hormonal contraception (progesterone only); * Successful vasectomy in the male partner (considered successful if a participant reports that a male partner has (i) documentation of azoospermia by microscopy, or (ii) a vasectomy more than 2 years ago with no resultant pregnancy despite unprotected sexual activity post vasectomy); * Or not be of reproductive potential, such as having reached menopause (no menses for 1 year without an alternative medical cause) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation. * Agree not to seek pregnancy including through alternative methods, such as artificial insemination or in vitro fertilization until 4 months after the IMP administration. 5. Participant who was born male, if heterosexually active male, using an effective method of contraception with their partner from the IMP administration until 4 months thereafter. All male participants also agree not to donate sperm during this period. 6. Negative nasopharyngeal antigenic test for SARS-CoV-2 on the day of screening and before randomisation 7. Participant who has normal biological values: * Hemoglobin ≥ 11.0 g/dL for participants who were born female, ≥ 13.0 g/dL for participants who were born male; * White blood cell count = 3,300 to 12,000 cells/mm3; * Total lymphocyte count ≥ 800 cells/mm3; * Platelets = 125,000 to 550,000/mm3; * ALT, AST, and alkaline phosphatase \< 1.25 times the institutional upper limit of normal; * Creatinine \<1.1x institutional upper limit of normal of the laboratory; * Normal urine test: absence of glucose, protein and haemoglobin * Negative HIV antigen/antibody test; * Negative Hepatitis B surface antigen (HBsAg); * Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive; 8. Willingness to undertake SARS-CoV-2 testing according to study protocol, and receive SARS-CoV-2 test results 9. Willingness and availability to be followed for the planned duration of the study in one of the dedicated trial centres 10. Informed and signed written consent form before performance of any trial-related screening procedures 11. Agree to be registered in the French Health Ministry computerised file (for France only) 12. Being covered by Health Insurance (for France only)
Exclusion criteria
1. Acute febrile infection (body temperature ≥ 38.0°C) within the previous 72 hours and/or presenting symptoms suggestive of COVID-19 or SARS-CoV-2 infection within the previous 28 days or having been in contact with an infected individual for the last 14 days before the inclusion visit 2. Any medical condition that could impair the immune response: clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to: * A process that would affect the immune response; * A process that would require medication that affects the immune response; * Any contraindication to repeated injections or blood draws; * A condition that requires active medical intervention or monitoring to avert grave danger to the participant's health or well-being during the study period; * A condition or process for which signs or symptoms could be confused with reactions to vaccine, or * Any condition specifically listed among the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety_Proportion of participants without any grade 3 or 4 adverse event | Between Day 0 and Week 4 | Proportion of participants without any grade 3 or 4 solicited local/systemic or unsolicited AEs between Day 0 and Week 4 and considered to be related or possibly related to IMP administration |
| Immunogenicity_Geometric mean titers of neutralizing antibodies | At Week 4 and Week 48 | Geometric mean titers of neutralizing antibodies against the original strain D614G and the relevant circulating variants measured at Week 4 and Week 48 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety_Number of Solicited local and systemic Adverse Reactions | up to Day 7 (7 days post vaccination) for local ARs and Week 2 (14 days post vaccination) for systemic ARs | overall; by grade |
| Safety_Number of Unsolicited adverse events | from Day 0 to end of trial | overall; by grade; by relationship to the vaccine |
| Safety_Number of Serious Adverse Events | from Day 0 to end of the trial | overall; by grade; by relationship to the vaccine |
| Immunogenicity_humoral immune response (IgG binding) | at Day 0 (before vaccination), Day 7, Week 2, Week 4, Week 12, Week 24, Week 36 and Week 48 | Geometric mean titers of IgG binding/neutralizing antibodies titers against the original strain D614G and the relevant circulating variants |
| Immunogenicity_persistence of immune imprinting | at Day 0 (before vaccination), Day 7, Week 2, Week 4, Week 12, Week 24, Week 36 and Week 48 | Estimation of the IgG ratio VOC/Wuhan |
| Immunogenicity_humoral immune response (neutralizing antibody titers) | at Day 0 (before vaccination), Day 7, Week 2, Week 4, Week 12, Week 24, Week 36 and Week 48 | Geometric mean titers of neutralizing antibodies titers against the original strain D614G and the relevant strain circulating |
| Immunogenicity_specific antibody responses | between Day 0 and Week 48 | Estimation and modelling of the slopes of antibody (binding and neutralizing) taking account all Ig measures collected during the follow-up |
| Immunogenicity_T-cell immunogenicity (polyfunctional cross reactive specific T-cells) | at Day 0 (before vaccination), Week 4, Week 12, Week 24, Week 36 and Week 48 | Cytokine expression patterns of T-cells measured by intracellular cytokine staining assay |
| Immunogenicity_durability of T-cell immune responses (polyfunctional cross reactive specific T-cells) | at Day 0 (before vaccination), Week 24 and Week 48 | Frequency of specific T-cell responses |
| Immunogenicity_correlation between the magnitude of CD4+ specific T-cell responses and levels of IgG specific responses | at Day 0 (before vaccination), Week 4, Week 12, Week 24, Week 36 and Week 48 | Frequency of specific CD4+ T-cell producing cytokines (ICS) and titers of binding and neutralizing antibody levels at the peak of IgG responses |
| Immunogenicity_repertoire of blood SARS-CoV-2 specific B-cells | at Day 0 (before vaccination), Day 7, Week 12, Week 24, and Week 48 | Frequency and breadth of the SARS-CoV-2 specific memory B-cell responses |
| Immunogenicity_innate immune responses | at Day 0 (before vaccination), Day 1, Day 7, Week 2, Week 4 and Week 12 | Correlation of innate immune responses to the different vaccines with the induction of long-lasting T- and B-cells adaptive immunity. Evaluation of the pre-vaccine innate immune profile and how it correlates with the magnitude, breadth, and durability of the adaptive immune response. Combined analysis of the mass cytometry cell specific analysis of the innate immune profile with the gene expression analysis performed at the same time points. |
| Immunogenicity_Gene expression | at Day 0 (before vaccination), Day 1, Day 7, Week 2, and Week 4 | Changes in gene expression at each time point. Comparison of changes in gene abundance at each time point versus baseline |
| Immunogenicity_T lymphocyte response | at Day 0 (before vaccination), Day 1, Day 7, Week 2, and Week 4 | Analysis of TCR profiles in the blood and on sorted specific T-cells by single-cell approach |
| Immunogenicity_mucosal immunity | at Day 0, Day 7, Week 4, Week 12, and Week 24 | Comparative analysis of anti-SARS-CoV-2 IgG and IgA mucosal antibody levels |
| Immunogenicity_T-cell memory responses | at Week 24 and Week 48 | Size (area) of the intradermal skin test reaction |
| Immunogenicity_serum levels of cytokine, chemokine and growth factor | at Day 0, Day 1, Day 7, Week 2, Week 4 and Week 12 | Correlation of the serum cytokine, chemokine and growth factor profile with the magnitude, breadth and durability of the adaptive immune response induced by the different vaccines. These data will be combined with innate immune and gene expression analysis to provide a comprehensive systems biology evaluation of the factors contributing to an effective vaccine candidate. |
Countries
France, Switzerland
Contacts
CONTACTYves LEVY, Pr
CONTACTGiuseppe PANTALEO, Pr
Outcome results
None listed