COVID-19 Vaccine
Conditions
Brief summary
The goals of this clinical trial are: 1. Phase 2: to test a gamma adapted recombinant vaccine against SARS-CoV-2 in healthy adult volunteers, previously vaccinated against the SARS-CoV-2 virus. 2. Phase 3 (first volunteer enrollement on March 25, 2023): to test a recombinant vaccine against SARS-CoV-2 comparing three different versions (Gamma Variant RBD-based ARVAC-CG vaccine, Omicron Variant RBD-based ARVAC-CG vaccine, Bivariant Gamma/Omicron RBD-based ARVAC-CG vaccine), in adult volunteers previously vaccinated against the SARS-CoV-2 virus The main questions to be answered are: 1. Phase 2: 1. What si the immune response after one dose of vaccine? 2. What is the safety and tolerability profile of this vaccine? 2. Phase 3 : 1. What is the immune response triggered by each vaccine formulation against Wuhan, gamma, and omicron variants. 2. What is the safety and tolerability profile of this vaccine? In phase 2, participants will receive one dose of the study vaccine and one dose of placebo 28 days apart, in a cross-over design. In phase 3 (not yet recruitment), participants will be randomized to receive one of the three possible types of vaccines and all of them will receive one dose of the corresponding vaccine and 1 dose of placebo 28 days apart, in a cross over design.
Interventions
BIOLOGICALGamma Variant RBD-based ARVAC-CG vaccine
Vaccine containing 50 µg of antigen + Alum. Schedule: One booster dose of vaccine Administration route: intramuscular (IM) injection
BIOLOGICALOmicron Variant RBD-based ARVAC-CG vaccine
Vaccine containing 50 µg of antigen + Alum. Schedule: One booster dose of vaccine Administration route: intramuscular (IM) injection
BIOLOGICALBivalent RBD-based ARVAC-CG vaccine
Vaccine containing 25 µg of gamma antigen + 25 µg of omicron antigen + Alum Schedule: One booster dose of vaccine Administration route: intramuscular (IM) injection
OTHERPlacebo (Alum)
Schedule: One dose of placebo in a crossover design Administration route: intramuscular (IM) injection
Sponsors
Universidad Nacional de San Martín (UNSAM)
National Council of Scientific and Technical Research, Argentina
Laboratorio Pablo Cassará S.R.L.
Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
In phase 2, participants will receive one dose of vaccine and one dose of placebo 28 days apart, in a cross over design. In phase 3, participants will be randomized to receive one of the three possible types of vaccines and all of them will receive one dose of the corresponding vaccine and 1 dose of placebo 28 days apart, in a cross over design.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
Yes
Inclusion criteria
\- All subjects who meet the following general criteria will be considered eligible for this trial: 1. Male or female participants greater than or equal to 18 years of age 2. With the ability and willingness to comply with the prohibitions and restrictions specified in the protocol. 3. Have received a complete vaccine regimen against SARS-CoV-2 with no more than one booster dose (last dose received at least 4 months prior to study entry). 4. In fertile female volunteers, negative pregnancy test at the beginning of the study and commitment to use a contraceptive method from the date of signing the consent form until 3 months after vaccine study application. Use of a hormonal contraceptive method must begin at least 28 days prior to study vaccine application. The investigator should assess potential contraceptive method failure (e.g. non-compliance, recent onset) in relation to vaccination. Acceptable effective methods for this study include: a) hormonal contraceptive method: i) combined (containing estrogen and progestin) associated with the inhibition of ovulation (oral, intravaginal or transdermal); ii) with progestin only, associated with the inhibition of ovulation (oral, injectable or implantable); b) intrauterine device; c) intrauterine hormone release system; d) bilateral tubal ligation/occlusion procedure; e) single couple with vasectomy; f) sexual abstinence, which will be considered effective only if it is defined as abstaining from heterosexual relations from the date of signing the consent until 3 months after receiving the study vaccine. The reliability of sexual abstinence should be assessed in relation to the duration of the study and the participant's usual and preferred lifestyle. 5. Participant who agrees to not donate bone marrow, blood or blood products until 3 months after the last dose of study vaccine; 6. Participant who is able to read, understand, and complete electronic questionnaires about signs and symptoms of COVID-19 surveillance; 7. Negative PCR or antigen test for the SARS-CoV-2 virus at enrollment time. 8. Capable of granting their informed consent signed and dated by the volunteer under study, and the authorized physician. Phase-specific inclusion criteria: Phase 2: 1\. Male or female participants between 18 and 60 years of age without known comorbidities. Phase 3: 1\. Male or female participants greater than or equal to 18 years of age with or without any chronic comorbidity stable and controlled based on the Investigator's judgment, not associated to a reduced immune response.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 - Immunogenicity - Seroconvertion rate | 14 days after vaccination | Seroconversion rate defined by a 4-fold increase from baseline of neutralizing antibody titer |
| Phase 3 - Immunogenicity - Seroconvertion rate | 14 days after vaccination | Seroconversion rate defined by a 4-fold increase from baseline of neutralizing antibody titer comparing the different arms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity - Neutralizing and total antibody titers | At baseline, 14 and 90 days after vaccination | Geometric Mean Titer (GMT) |
| Safety - Solicited local and systemic reactions after vaccination | Day 0 to 7 days after vaccination | Number of volunteers overall and in each vaccination group with local or systemic vaccine reactogenicity, based on evaluacion of solicited adverse events (AEs) recorded on subject memory aids o during clinical assessments |
| Safety - Serious Adverse Events | Day 0 to 30 days after vaccination | Number of volunteers overall and in each vaccination group with vaccine associated serioius adverse events (SAEs) |
| Safety - Variations in laboratory results | At 30 days after vaccination | Number of volunteers overall and in each vaccination group with variations in laboratory results from a baseline control |
| Safety - Unsolicited adverse events after vaccination | Day 0 to 30 days after vaccination | Number of volunteers overall and in each vaccination group |
| Immunogenicity - Neutralizing antibody titer | 14 days after vaccination | Proportion of individuals whith at least 8-fold increase from baseline |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory - Antibody Titers in saliva | At baseline and day 14 after vaccination | Antigen specific antibodies in a selected subpopulation |
| Exploratory - Immunogenicity | At baseline and 14 days after vaccination | Number of interferon (IFN) gamma producing cells directed to Receptor Binding Domain (RBD) (Spike protein region) |
Countries
Argentina
Outcome results
None listed