ARVAC-A New Recombinant Coronavirus Disease 2019 (COVID-19) Vaccine

COVID-19 Vaccine Clinical Trial

— ARVAC-F2/3  

Official title:

Phase 2/3 Study to Evaluate Safety, Tolerability and Immunogenicity of a Recombinant Protein-based Vaccine Against SARS-CoV-2, in a Population of Adult Volunteers Previously Vaccinated Against SARS-CoV-2 Virus.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05752201
• Other study ID #: ARVAC-F2/3-002
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: February 6, 2023
• Est. completion date: December 7, 2023

Study information

• Verified date: December 2023
• Source: Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2014
• Est. completion date: December 7, 2023
• Est. primary completion date: August 22, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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:

• Exclusion Criteria:

1. History of SARS-CoV-2 infection or known previous disease, within 90 days prior to study entry (at least 90 days from epidemiological discharge).

2. Administration of any commercial or not commercial vaccine, based on:

1. Live attenuated virus within 28 days prior to study entry.

2. Killed virus within 14 days prior to study entry.

3. Individuals that have not received a complete primary vaccination schedule against SARS-CoV-2 virus (1 or 2 doses, depending on the vaccine used in the primary schedule).

4. Administration of complete primary vaccination schedule against SARS-CoV-2 virus (1 or 2 doses, depending on the vaccine received) or a booster dose, within 4 months prior to the start of the study.

5. Administration of more than one booster dose after a complete primary vaccination schedule against SARS-CoV-2 virus.

6. Individuals that have scheduled to receive any other commercial vaccine in the following 3 months after receiving the study vaccine dose.

7. Individuals that have participated in a research study within 60 days prior to the start of the study.

8. History of known allergies or a history of anaphylaxis or any other serious adverse reaction with other vaccines or their excipients.

9. History of alcoholism or substance abuse that prevents compliance with the characteristics of the protocol.

10. Acute infectious disease at enrollment (this does not include minor conditions such as diarrhea or mild upper respiratory tract illness) or temperature =38. 0°C within 24 hours prior to scheduled study vaccination; later admission is permitted at the discretion of the investigator and after the Sponsor agreement.

11. Body Mass Index (BMI) greater than 35 kg/m2.

12. History of any clinical condition that affects the function of the immune system, including, but not limited to:

1. Clinical conditions (e.g. autoimmune disease or possibly immune-mediated disease or known or suspected immunodeficiency; diabetes mellitus type I or II, chronic kidney disease, etc.).

2. Chronic or recurrent use of systemic corticosteroids in the 6 months prior to study vaccine administration and during the study. A substantially immunosuppressive dose of steroids is considered =2 weeks of daily administration of 20 mg prednisone or equivalent.

3. Administration of antineoplastic and immunomodulatory agents or radiation therapy within 6 months prior to study vaccine administration or during the study.

13. The volunteer has any contraindication to receive intramuscular injections and/or blood draws.

14. The volunteer has received an investigational drug (including drugs related to COVID-19 prophylaxis) or used an investigational invasive medical device in the past 30 days or has received investigational immunoglobulin or monoclonal antibodies within 3 months (participation in an observational study is allowed at the discretion of the investigator, previously informing the Sponsor about this decision).

15. The volunteer has a history of acute polyneuropathy (e.g. Guillain Barré syndrome).

16. The volunteer underwent a surgical procedure that required hospitalization (defined as hospitalization for more than 24 hours or overnight hospitalization), in the 12 weeks prior to vaccination, or has not recovered completely from surgery that required hospitalization or is scheduled for surgery that will require hospitalization during the time he/she is expected to participate in the study or within 6 months of study vaccine administration.

17. The participant is pregnant, plans to become pregnant within 3 months after the administration of the vaccine, or is in postpartum or lactation period.

18. Any condition or finding regarding the participant that, in the opinion of the researcher, could put the subject under investigation at risk, or interfere with the interpretation of the results of the study.

Some events may be considered only a temporary contraindication to receiving the study vaccine. Such is the case of:

• Clinically significant acute illness at the time of vaccination. This does not include minor illnesses such as diarrhea or a mild respiratory tract infection.

• Fever (temperature =38.0°C) in the 24 hours prior to the application of the vaccine under study. A disease that, in the opinion of the investigator, may interfere with the reactogenicity/safety evaluations of the first days after the study vaccine.

If any of these events occur at the time of vaccination, vaccination may be postponed until resolution of the event, provided that it occurs within the permitted screening period (15 days of initial testing). If the box is resolved beyond the allowed window of the selection, all initial analyses must be repeated.

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Vaccine

Intervention

Biological:
• Gamma Variant RBD-based ARVAC-CG vaccine
Vaccine containing 50 µg of antigen + Alum. Schedule: One booster dose of vaccine Administration route: intramuscular (IM) injection
• Omicron Variant RBD-based ARVAC-CG vaccine
Vaccine containing 50 µg of antigen + Alum. Schedule: One booster dose of vaccine Administration route: intramuscular (IM) injection
• Bivalent 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

Other:
• Placebo (Alum)
Schedule: One dose of placebo in a crossover design Administration route: intramuscular (IM) injection

Locations

Country	Name	City	State
Argentina	Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" - CEMIC	Argentina	C.a.b.a.
Argentina	Centro Clínica del Niño y la Familia	Buenos Aires
Argentina	Instituto de Investigaciones Clínicas de Mar del Plata	Buenos Aires
Argentina	Instituto Medico Platense	Buenos Aires
Argentina	Centro de Investigaciones Clínicas Belgrano (CICB)	Ciudad Autonoma de Buenos Aires	Ciudad De Buenos Aires
Argentina	FP Clinical Pharma	Ciudad Autonoma de Buenos aires
Argentina	Vacunar S.A.	Ciudad Autonoma de Buenos Aires
Argentina	Fundación Huesped	Ciudad Autónoma de Buenos Aires	Caba
Argentina	Centro Médico Dra. Laura Maffei - Investigación Clínica Aplicada	Ciudad de Buenos Aires
Argentina	Clinica Privada del Sol	Córdoba	Cordoba
Argentina	ICSAL Salta	Salta

Sponsors (4)

Lead Sponsor	Collaborator
Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno	Laboratorio Pablo Cassará S.R.L., National Council of Scientific and Technical Research, Argentina, Universidad Nacional de San Martín (UNSAM)

Country where clinical trial is conducted

Argentina, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory - Antibody Titers in saliva	Antigen specific antibodies in a selected subpopulation	At baseline and day 14 after vaccination
Other	Exploratory - Immunogenicity	Number of interferon (IFN) gamma producing cells directed to Receptor Binding Domain (RBD) (Spike protein region)	At baseline and 14 days after vaccination
Primary	Phase 2 - Immunogenicity - Seroconvertion rate	Seroconversion rate defined by a 4-fold increase from baseline of neutralizing antibody titer	14 days after vaccination
Primary	Phase 3 - Immunogenicity - Seroconvertion rate	Seroconversion rate defined by a 4-fold increase from baseline of neutralizing antibody titer comparing the different arms	14 days after vaccination
Secondary	Immunogenicity - Neutralizing antibody titer	Proportion of individuals whith at least 8-fold increase from baseline	14 days after vaccination
Secondary	Immunogenicity - Neutralizing and total antibody titers	Geometric Mean Titer (GMT)	At baseline, 14 and 90 days after vaccination
Secondary	Safety - Solicited local and systemic reactions 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	Day 0 to 7 days after vaccination
Secondary	Safety - Unsolicited adverse events after vaccination	Number of volunteers overall and in each vaccination group	Day 0 to 30 days after vaccination
Secondary	Safety - Serious Adverse Events	Number of volunteers overall and in each vaccination group with vaccine associated serioius adverse events (SAEs)	Day 0 to 30 days after vaccination
Secondary	Safety - Variations in laboratory results	Number of volunteers overall and in each vaccination group with variations in laboratory results from a baseline control	At 30 days after vaccination