Study of a Recombinant Coronavirus-Like Particle COVID-19 Vaccine in Adults

SARS-CoV-2 Infection Clinical Trial

Official title:

Randomized, Observer-Blind, Placebo-Controlled, Phase 2/3 Study to Assess the Safety, Efficacy, and Immunogenicity of a Recombinant Coronavirus-Like Particle COVID-19 Vaccine in Adults 18 Years of Age or Older

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04636697
• Other study ID #: CP-PRO-CoVLP-021
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: November 19, 2020
• Est. completion date: April 30, 2022

Study information

• Verified date: June 2021
• Source: Medicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase 2/3 study is a multi-portion design to confirm that the chosen formulation and dosing regimen of CoVLP has an acceptable immunogenicity and safety profile.

The Phase 3 portion is an event-driven, randomized, observer blinded, placebo-controlled design that will evaluate the efficacy and safety of the CoVLP formulation compared to placebo.

Subjects will be followed for safety and immunogenicity for a period of 12 months after the last vaccination.

Other known NCT identifiers

• NCT04662697

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30918
• Est. completion date: April 30, 2022
• Est. primary completion date: August 25, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Subjects must have read, understood, and signed the informed consent form (ICF) prior to participating in the study; subjects must also complete study-related procedures and the subjects must communicate with the study staff at visits and by phone during the study;

2. At the Screening visit (Visit 1), male and female subjects must be:

• Study Populations #1: 18 to 64 (has not yet had his/her 65th birthday) years of age, inclusive;

• Study Population #2: 65 years of age or older;

• Study Population #3: 18 years of age or older;

3. At Screening (Visit 1) and Vaccination (Visit 2), subject must have a body mass index (BMI) of:

• Study Populations #1 and #2: = 18.5 and < 30 kg/m2;

4. Subjects are considered by the Investigator to be reliable and likely to cooperate with the assessment procedures and be available for the duration of the study;

5. Study Population #1: Subjects must be in good general health prior to study participation, with no clinically relevant abnormalities that could jeopardize subject safety or interfere with study assessments, as determined by medical history, physical examination, and vital signs. Investigator discretion will be permitted with this inclusion criterion;

All regions except Canada: Note: Subjects with a pre-existing chronic disease will be allowed to participate if the disease is stable and, according to the Investigator's judgment that must be documented in the source documents, the condition is unlikely to confound the results of the study or pose additional risk to the subject by participating in the study. Stable disease is generally defined as no new onset or exacerbation of pre-existing chronic disease three months prior to vaccination. Based on the Investigator's judgment, a subject with more recent stabilization of a disease could also be eligible.

6. Study Populations #1 and #3: Female subjects of childbearing potential must have a negative serum pregnancy test result at Screening (Visit 1 for the Phase 2 portion) and/or a negative urine pregnancy test result at Vaccination (Visit 2 for the Phase 2 portion; Visit 1 for the Phase 3 portion):

Non-childbearing females are defined as:

• Surgically-sterile (defined as bilateral tubal ligation, hysterectomy or bilateral oophorectomy performed more than one month prior to the first study vaccination); or

• Post-menopausal (absence of menses for 12 consecutive months and age consistent with natural cessation of ovulation);

7. Study Populations #1 and #3: Female subjects of childbearing potential must use an effective method of contraception for one month prior to vaccination (Visit 2) and agree to continue employing highly effective birth control measures for at least one month after the last study vaccination (or in the case of early termination, she must not plan to become pregnant for at least one month after her last study vaccination).

The following relationship or methods of contraception are considered to be highly effective:

• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

• Oral;

• Intravaginal;

• Transdermal;

• Progestogen-only hormonal contraception associated with inhibition of ovulation:

• Oral;

• Injectable;

• Implantable;

• Intra-uterine device with or without hormonal release;

• Credible self-reported history of heterosexual vaginal intercourse abstinence prior to and for at least one month after the last study vaccination. Abstinent subjects who are ovulating should be asked what method(s) they would use should their circumstances change, and subjects without a well-defined plan should be excluded;

• Female partner;

• All regions except the US: Vasectomised partner, provided that this partner is the sole sexual partner of the study participant and that the vasectomised partner has received a medical assessment of the surgical success;

• Bilateral tubal ligation.

8. Study Population #2: Subjects must be non-institutionalized (e.g. not living in rehabilitation centres or old-age homes; living in an elderly community is acceptable) and have no acute or evolving medical problems prior to study participation and no clinically relevant abnormalities that could jeopardize subject safety or interfere with study assessments, as assessed by the Principal Investigator or sub-Investigator (thereafter referred as Investigator) and determined by medical history, physical examination, serology (only for the Phase 2 portion), clinical chemistry and haematology tests (only for the Phase 2 portion), urinalysis (only for the Phase 2 portion), and vital signs. Investigator discretion will be permitted with this inclusion criterion.

All regions except Canada: Note: Subjects with a pre-existing chronic disease will be allowed to participate if the disease is stable and, according to the Investigator's judgment that must be documented in the source documents, the condition is unlikely to confound the results of the study or pose additional risk to the subject by participating in the study. Stable disease is generally defined as no new onset or exacerbation of pre-existing chronic disease three months prior to vaccination. Based on the Investigator's judgment and documented in source documentation, a subject with more recent stabilization of a disease could also be eligible;

9. Study Population #3: Subjects must have one or more co-morbid conditions that puts them at higher risk for severe COVID-19 disease. These comorbidities include but are not limited to obesity, hypertension, type 1 or type 2 diabetes, chronic obstructive pulmonary disease (COPD), cardiovascular diseases, chronic kidney diseases, or be immunocompromised persons (e.g., treatment-controlled HIV infection, organ transplant recipients, or patients receiving cancer chemotherapy). Investigator discretion will be permitted with this inclusion criterion.

Exclusion criteria:

1. Study Populations #1 and #2: According to the Investigator's opinion, significant acute or chronic, uncontrolled medical or neuropsychiatric illness.

Acute disease is defined as presence of any moderate or severe acute illness with or without a fever within 48 hours prior to the Screening (Visit 1) and/or Vaccination visit (Visit 2). 'Uncontrolled' is defined as:

• Requiring a new medical or surgical treatment during the three months prior to study vaccine administration;

• Requiring any significant change in a chronic medication (i.e. drug, dose, frequency) during the three months prior to study vaccine administration due to uncontrolled symptoms or drug toxicity unless the innocuous nature of the medication change meets the criteria outlined in inclusion criterion no. 5 (Study Population #1) or no. 8 (Study Population #2) and is appropriately justified and documented by the Investigator.

Investigator discretion is permitted with this exclusion criterion and must be carefully and fully documented in the source documents;

2. Study Populations #1 and #2: Any chronic medical condition associated with elevated risk of severe outcomes of COVID-19, including obesity, diabetes (type 1 or type 2), significant cardiovascular or respiratory diseases including asthma, chronic renal failure, disorders of bleeding/coagulation, chronic inflammatory or autoimmune conditions, immunosuppressive conditions (including HIV), and hypertension;

3. Study Populations #1 and #2: Any confirmed or suspected current immunosuppressive condition or immunodeficiency, including cancer, human immunodeficiency virus (HIV), hepatitis B or C infection (subjects with a history of cured hepatitis B or C infection without any signs of immunodeficiency at present time are allowed). Investigator discretion is permitted with this exclusion criterion;

4. Study Populations #1 and #2: Current autoimmune disease (such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis or narcolepsy). Investigator discretion is permitted with this exclusion criterion, and subjects may be eligible to participate with appropriate written justification in the source document (i.e. subjects with a history of autoimmune disease who are disease-free without treatment for three years or more, or on stable thyroid replacement therapy, mild psoriasis [i.e. a small number of minor plaques requiring no systemic treatment], etc.);

5. Study Populations #1 and #2: Administration of any medication or treatment that may alter the vaccine immune responses, such as:

• Systemic glucocorticoids at a dose exceeding 10 mg of prednisone (or equivalent) per day for more than seven consecutive days or for 10 or more days in total, within one month prior to the Vaccination visit (Visit 2). Inhaled, nasal, ophthalmic, dermatological, and other topical glucocorticoids are permitted;

• Cytotoxic, antineoplastic, or immunosuppressant drugs - within 36 months prior to Vaccination (Visit 2);

• Any immunoglobulin preparations or blood products, blood transfusion - within 6 months prior to Vaccination (Visit 2);

6. Study Population #3: Acute disease defined as presence of any moderate or severe acute illness with or without a fever within 48 hours prior to the Screening (Visit 1) and/or Vaccination visit (Visit 2);

7. Administration of any vaccine within 14 days prior to Vaccination (Visit 2); planned administration of any vaccine during the study (up to Day 28 of the study). Immunization on an emergency basis during the study will be evaluated on case-by-case basis by the Investigator;

8. Administration of any other SARS-CoV-2 / COVID-19, or other experimental coronavirus vaccine at any time prior to or during the study;

9. History of virologically-confirmed COVID-19;

10. Use of any investigational or non-registered product within 30 days or 5 half-lives, whichever is longer, prior to Vaccination (Visit 2) or planned use during the study period. Subjects who are in a prolonged post-administration observation period of another investigational or marketed drug clinical study, for which there is no ongoing exposure to the investigational or marketed product and all scheduled on-site visits are completed, will be allowed to take part in this study, if all other eligibility criteria are met;

11. Have a rash, dermatological condition, tattoos, muscle mass, or any other abnormalities at injection site that may interfere with injection site reaction rating. Investigator discretion will be permitted with this exclusion criterion;

12. Use of any prescription antiviral drugs with the intention of COVID-19 prophylaxis, including those that are thought to be effective for prevention of COVID-19 but have not been licensed for this indication, within one month prior to Vaccination (Visit 2);

13. For the Phase 2 portion of the study only: Use of prophylactic medications (e.g. antihistamines [H1 receptor antagonists], nonsteroidal anti-inflammatory drugs [NSAIDs], systemic and topical glucocorticoids, non-opioid and opioid analgesics) within 24 hours prior to the Vaccination (Visit 2) to prevent or pre-empt symptoms due to vaccination;

14. History of a serious allergic response to any of the constituents of CoVLP including AS03;

15. History of a documented anaphylactic reactions to plants or plant components (including tobacco, fruits and nuts);

16. Personal or family history of narcolepsy;

17. Subjects with a history of Guillain-Barré Syndrome;

18. Study Populations #1 and #3: Any female subject who has a positive or doubtful pregnancy test result prior to vaccination or who is lactating;

19. Subjects identified as an Investigator or employee of the Investigator or clinical site with direct involvement in the proposed study, or identified as an immediate family member (i.e. parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study, or any employees of Medicago.

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV-2 Infection

Intervention

Drug:
• Intramuscular injection
Subjects will receive two doses of placebo given 21 days apart into the deltoid region of the alternating arm (each arm will be injected once)

Biological:
• Intramuscular vaccine
Subjects will receive two doses of 3.75 µg of CoVLP adjuvanted with AS03 adjuvant given 21 days apart into the deltoid region of the alternating arm (each arm will be injected once)

Locations

Country	Name	City	State
Argentina	Fundación FunDaMos	Buenos Aires
Argentina	Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich	Buenos Aires
Argentina	Mautalen Salud e Investigación (Expertia SA)	Buenos Aires
Argentina	Sanatorio Allende	Córdoba
Argentina	Clinica Mayo de UMCB SRL	San Miguel De Tucumán
Brazil	Instituto de Pesquisas Clinicas L2IP	Brasília
Brazil	Unidade Hospital do Rocio	Campo Largo
Brazil	Santa Casa De Misericordia De Belo Horizonte	Minas Gerais
Brazil	Centro de Pesquisa Clinica - Hospital Moinhos de Vento	Porto Alegre
Brazil	IBPClin Instituto Brasil de Pequisa Clinica	Rio De Janeiro
Brazil	Fundação Faculdade Regional de Medicina de Sao Jose do Rio Preto	São Paulo
Brazil	Azidus Brasil Pesquisa e Desenvolvimento Ltda	Valinhos
Canada	Aggarwal and Associates Ltd	Brampton	Ontario
Canada	Dawson Clinical Research Inc.	Guelph	Ontario
Canada	IWK Health Centre- Dalhousie University-Canadian Center for Vaccinology	Halifax	Nova Scotia
Canada	Manna Research (Quebec)	Lévis	Quebec
Canada	Manna Research (Mirabel)	Mirabel	Quebec
Canada	SKDS Research Inc.	Newmarket	Ontario
Canada	McGill University Health Centre Vaccine Study Centre	Pierrefonds	Quebec
Canada	Diex Research Quebec Inc.	Québec	Quebec
Canada	CHU de Québec-Université Laval	Québec City	Quebec
Canada	CARe Clinic	Red Deer	Alberta
Canada	Diex Recherche Joliette	Saint-Charles-Borromée	Quebec
Canada	Diex Recherche Sherbrooke	Sherbrooke	Quebec
Canada	Q&T Research Sherbrooke Inc.	Sherbrooke	Quebec
Canada	LMC Clinical Research Inc. (CPU)	Toronto	Ontario
Canada	Manna Research Toronto	Toronto	Ontario
Mexico	Investigación Biomédica para el Desarrollo de Fármacos, S.A. de C.V.	Aguascalientes
Mexico	RM Pharma Specialists S.A. de C.V.	Ciudad de México
Mexico	Centro para el Desarrollo de la Medicina y de Asistencia Médica Especializada S.C.	Culiacán
Mexico	Centro Multidisciplinario para el Desarrollo Especializado de la Investigación Clínica en Yucatan S.C.P. (CEMDEICY S.C.P.)	Mérida
Mexico	Integra RGH Centro de Investigacion, Clinica de Ozonoterapia RGH AC	Puebla
Mexico	Sociedad de Metabolismo y Corazon S.C (SOMECO)	Veracruz
Mexico	Investigación Biomédica para el Desarrollo de Fármacos, S.A. de C.V.	Zapopan
United Kingdom	NHS Grampian	Aberdeen
United Kingdom	Synexus Midlands Clinical Research Centre	Birmingham
United Kingdom	University Hospital Southampton NHS Foundation Trust (UHS)	Bournemouth
United Kingdom	Public Health Wales	Cardiff
United Kingdom	Synexus Wales DRS	Cardiff
United Kingdom	Mid and South Essex NHS Foundation Trust	Chelmsford
United Kingdom	Synexus Lancashire DRS	Chorley
United Kingdom	University Hospitals Derby and Burton	Derby
United Kingdom	London North West University Healthcare NHS Trust	Harrow
United Kingdom	Kings College Hospital	London
United Kingdom	Synexus Manchester DRS	Manchester
United Kingdom	University of York/York Teaching Hospital	York
United States	Benchmark Research	Austin	Texas
United States	Tekton Research	Austin	Texas
United States	Hassman Research Institute	Berlin	New Jersey
United States	Achieve Clinical Research, LLC dba Accel Research Sites	Birmingham	Alabama
United States	Hope Clinical Research	Canoga Park	California
United States	Affinity Health	Chicago	Illinois
United States	Velocity Clinical Research - Cincinnati	Cincinnati	Ohio
United States	Velocity Clinical Research	Cleveland	Ohio
United States	Aventiv Research Inc	Columbus	Ohio
United States	Alliance for Multispecialty Research	Coral Gables	Florida
United States	Benchmark Research	Covington	Louisiana
United States	Global Medical Research	Dallas	Texas
United States	Meridian Clinical Research	Endwell	New York
United States	Carolina Institute for Clinical Research	Fayetteville	North Carolina
United States	Benchmark Research	Fort Worth	Texas
United States	Methodist Physicians	Fremont	Nebraska
United States	CNS Network	Garden Grove	California
United States	Ascension St. John Vaccine Research Unit	Grosse Pointe Woods	Michigan
United States	Research Centers of America	Hollywood	Florida
United States	Excel Clinical Research	Las Vegas	Nevada
United States	Forte Family Practice/ CCT Research	Las Vegas	Nevada
United States	Be Well Clinical Studies, LLC	Lincoln	Nebraska
United States	Long Beach Clinical Trial Services Inc.	Long Beach	California
United States	AppleMed Research Inc	Miami	Florida
United States	ASR, LLC	Nampa	Idaho
United States	Pharmacology Research Institute	Newport Beach	California
United States	Meridian Clinical Research LLC	Norfolk	Nebraska
United States	Las Vegas Clinical Trials	North Las Vegas	Nevada
United States	South Ogden Family Medicine	Ogden	Utah
United States	Meridian Clinical Research LLC	Omaha	Nebraska
United States	Elixia COVID-19	Palm Beach	Florida
United States	Research Your Health	Plano	Texas
United States	M3 Wake Research, Inc	Raleigh	North Carolina
United States	Wr-McCr, Llc	San Diego	California
United States	Meridian Clinical Research	Savannah	Georgia
United States	Meridian Clinical Research	Sioux City	Iowa
United States	Mt. Olympus Medical Research, LLC	Sugar Land	Texas
United States	Sugar Lakes Family Practice	Sugar Land	Texas
United States	Precision Clinical Research	Sunrise	Florida
United States	Fiel Family and Sports Medicine/CCT	Tempe	Arizona
United States	DM Clinical Research/Martin Diagnostic Clinic	Tomball	Texas
United States	Velocity Clinical Research Providence	Warwick	Rhode Island
United States	Ascension Providence Health System	Washington	District of Columbia
United States	Advanced Clinical Research, Inc.	West Jordan	Utah
United States	Trial Management Associates LLC	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Medicago

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Mexico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 2 portion: Immediate adverse event (AEs)	Percentage, intensity, and relationship to vaccination of immediate AEs	30 minutes
Primary	Phase 2 portion: Solicited local and systemic adverse events (AEs)	Percentage, intensity, and relationship to vaccination of solicited local and systemic AEs	7 days
Primary	Phase 2 portion: Unsolicited adverse events (AEs)	Percentage, intensity, and relationship of unsolicited AEs	21 days
Primary	Phase 2 portion: Number of subjects with normal and abnormal clinically significant urine values	Number of subjects with normal and abnormal clinically significant urine values	3 days
Primary	Phase 2 portion: Number of subjects with normal and abnormal clinically significant haematological values	Number of subjects with normal and abnormal clinically significant haematological values	3 days
Primary	Phase 2 portion: Number of subjects with normal and abnormal clinically significant biochemical values	Number of subjects with normal and abnormal clinically significant biochemical values	3 days
Primary	Phase 2 portion: Percentage of subjects with normal and abnormal clinically significant urine values	Percentage of subjects with normal and abnormal clinically significant urine values	3 days
Primary	Phase 2 portion: Percentage of subjects with normal and abnormal clinically significant haematological values	Percentage of subjects with normal and abnormal clinically significant haematological values	3 days
Primary	Phase 2 portion: Percentage of subjects with normal and abnormal clinically biochemical values	Percentage of subjects with normal and abnormal clinically biochemical values	3 days
Primary	Phase 2 portion: Serious adverse events (SAEs), adverse events (AEs) leading to withdrawal, adverse event of special interest (AESI) (including vaccine-enhanced disease) and deaths	Percentage of SAEs, MAAEs, AEs leading to withdrawal, AESIs (including VED), and deaths	21 days
Primary	Phase 2 portion: Neutralizing antibody (Nab assay) response	Nab response induced in each Study Population against the SARS-CoV-2 virus	Day 21
Primary	Phase 2 portion: Neutralizing antibody (Nab assay) response	Nab response induced in each Study Population against the SARS-CoV-2 virus	Day 42
Primary	Phase 2 portion:Specific Th1 cell-mediated immunity (CMI) response	Specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 , as measured by IFN-? ELISpot	Day 21
Primary	Phase 2 portion:Specific Th1 cell-mediated immunity (CMI) response	Specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 , as measured by IFN-? ELISpot	Day 42
Primary	Phase 3 portion: Laboratory-confirmed (virologic method) symptomatic SARS-CoV-2 infection	First occurrence, in a subject, of laboratory-confirmed (virologic method) symptomatic SARS-CoV-2 infection	Day 28 and after
Secondary	Phase 2 portion: Solicited local and systemic AEs (populations 1 and 2)	Relative percentage of solicited local and systemic AEs following each vaccine administration between the healthy adults (Study Population #1) and the healthy elderly population (Study Population #2, each age strata);	7 days
Secondary	Phase 2 portion: Solicited local and systemic AEs (populations 1, 2 and 3)	Relative percentage of solicited local and systemic AEs by intensity grades for seven days following each vaccine administration between the healthy adults (Study Population #1) and the healthy elderly adults (Study Population #2) combined and the adults with significant comorbidities (Study Population #3)	7 days
Secondary	Phase 2 portion: Serious adverse events (SAEs), medically attended adverse events (MAAEs), adverse events (AEs) leading to withdrawal, adverse event of special interest (AESI) (including vaccine-enhanced disease) and deaths	Percentage of SAEs, MAAEs, AEs leading to withdrawal, AESIs (including VED), and deaths	Day 43 to 386
Secondary	Phase 3 portion: Immediate adverse event (AEs)	Percentage, intensity, and relationship to vaccination of immediate AEs	30 minutes
Secondary	Phase 3 portion: Solicited local and systemic AEs	Percentage, intensity, and relationship to vaccination of solicited local and systemic AEs	7 days
Secondary	Phase 3 portion: Unsolicited adverse events (AEs)	Percentage, intensity, and relationship of unsolicited AEs	21 days
Secondary	Phase 3 portion: Serious adverse events (SAEs), adverse events (AEs) leading to withdrawal, adverse event of special interest (AESI) (including vaccine-enhanced disease) and deaths	Percentage of SAEs, MAAEs, AEs leading to withdrawal, AESIs (including VED), and deaths	Day 0 to 386
Secondary	Phase 2 portion: Neutralizing antibody Geometric mean tiers (GMT) response (populations 1 and 2)	Relative neutralizing antibody response between the healthy adults (Study Population #1) and the healthy elderly population (Study Population #2; each age strata) will be analyzed using the Following parameter: Geometric mean tiers (GMT)	21 days
Secondary	Phase 2 portion: Neutralizing antibody Geometric mean tiers (GMT) response (populations 1, 2 and 3)	• Relative neutralizing antibody response between the healthy adults (Study Population #1) and the healthy elderly adults (Study Population #2) combined and the adults with significant comorbidities (Study Population #3) will be analyzed using the Following parameter: Geometric mean tiers (GMT)	21 days
Secondary	Phase 2 portion: Neutralizing antibody (Nab assay) response	Persistence of the Nab antibody response induced in each Study Population against the SARS-CoV-2 virus	Day 128
Secondary	Phase 2 portion: Neutralizing antibody (Nab assay) response	Persistence of the Nab antibody response induced in each Study Population against the SARS-CoV-2 virus	Day 201
Secondary	Phase 2 portion: Neutralizing antibody (Nab assay) response	Persistence of the Nab antibody response induced in each Study Population against the SARS-CoV-2 virus	Day 386
Secondary	Phase 2 portion: Specific antibody (IgG) response	Specific antibody response induced in each Study Population against the SARS-CoV-2 virus will be measured by the total IgG levels	Day 128
Secondary	Phase 2 portion: Specific antibody (IgG) response	Specific antibody response induced in each Study Population against the SARS-CoV-2 virus will be measured by the total IgG levels	Day 201
Secondary	Phase 2 portion: Specific antibody (IgG) response	Specific antibody response induced in each Study Population against the SARS-CoV-2 virus will be measured by the total IgG levels	Day 386
Secondary	Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 21
Secondary	Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 42
Secondary	Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 128
Secondary	Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 201
Secondary	Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 386
Secondary	Phase 2 portion: Specific Th1 cell-mediated immunity (CMI) response	Specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IFN-? ELISpot	Day 201
Secondary	Phase 2 portion: Specific Th1 cell-mediated immunity (CMI) response	Specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IFN-? ELISpot	Day 386
Secondary	Phase 2 portion: Specific Th2 cell-mediated immunity (CMI) response	Specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 21
Secondary	Phase 2 portion: Specific Th2 cell-mediated immunity (CMI) response	Specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 42
Secondary	Phase 2 portion: Specific Th2 cell-mediated immunity (CMI) response	Specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 201
Secondary	Phase 2 portion: Specific Th2 cell-mediated immunity (CMI) response	Specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 386
Secondary	Phase 3 portion: Neutralizing antibody Geometric mean titers (GMT) response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean titers (GMT)	Day 21
Secondary	Phase 3 portion: Neutralizing antibody Seroconversion (SC) rate response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 21
Secondary	Phase 3 portion: Neutralizing antibody Geometric mean fold rise (GMFR) response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean fold rise (GMFR)	Day 21
Secondary	Phase 3 portion: Neutralizing antibody Geometric mean titers (GMT) response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean titers (GMT)	Day 42
Secondary	Phase 3 portion: Neutralizing antibody Seroconversion (SC) rate response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 42
Secondary	Phase 3 portion: Neutralizing antibody Geometric mean fold rise (GMFR) response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean fold rise (GMFR)	Day 42
Secondary	Phase 3 portion: Neutralizing antibody Geometric mean fold rise (GMFR) response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean fold rise (GMFR)	Day 201
Secondary	Phase 3 portion: Neutralizing antibody Geometric mean titers (GMT)	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean titers (GMT)	Day 201
Secondary	Phase 3 portion: Neutralizing antibody Seroconversion (SC) rate response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 201
Secondary	Phase 3 portion: Neutralizing antibody Geometric mean fold rise (GMFR) response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean fold rise (GMFR)	Day 386
Secondary	Phase 3 portion: Neutralizing antibody Geometric mean titers (GMT) response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean titers (GMT)	Day 386
Secondary	Phase 3 portion: Neutralizing antibody Seroconversion (SC) rate response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 386
Secondary	Phase 3 portion: Specific antibody (IgG) response	In a subset of subjects, specific antibody response induced in each Study Population against the SARS-CoV-2 virus measured by the total IgG levels	Day 21
Secondary	Phase 3 portion: Specific antibody (IgG) response	In a subset of subjects, specific antibody response induced in each Study Population against the SARS-CoV-2 virus measured by the total IgG levels	Day 42
Secondary	Phase 3 portion: Specific antibody (IgG) response	In a subset of subjects, specific antibody response induced in each Study Population against the SARS-CoV-2 virus measured by the total IgG levels	Day 201
Secondary	Phase 3 portion: Specific antibody (IgG) response	In a subset of subjects, specific antibody response induced in each Study Population against the SARS-CoV-2 virus measured by the total IgG levels	Day 386
Secondary	Phase 3 portion: Neutralizing antibody titers: IgG ELISA antibody titers	In a subset of subjects, the ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 21
Secondary	Phase 3 portion: Neutralizing antibody titers: IgG ELISA antibody titers	In a subset of subjects, the ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 42
Secondary	Phase 3 portion: Neutralizing antibody titers: IgG ELISA antibody titers	In a subset of subjects, the ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 201
Secondary	Phase 3 portion: Neutralizing antibody titers: IgG ELISA antibody titers	In a subset of subjects, the ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 386
Secondary	Phase 3 portion: Specific Th1 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IFN-? ELISpot	Day 21
Secondary	Phase 3 portion: Specific Th1 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IFN-? ELISpot	Day 42
Secondary	Phase 3 portion: Specific Th1 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IFN-? ELISpot	Day 201
Secondary	Phase 3 portion: Specific Th1 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IFN-? ELISpot	Day 386
Secondary	Phase 3 portion: Specific Th2 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 21
Secondary	Phase 3 portion: Specific Th2 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 42
Secondary	Phase 3 portion: Specific Th2 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 201
Secondary	Phase 3 portion: Specific Th2 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 386
Secondary	Phase 2 portion: Laboratory-confirmed (virologic method) symptomatic SARS-CoV-2 infection	First occurrence, in a subject, of laboratory-confirmed (virologic method) symptomatic SARS-CoV-2 infection	Day 28 to 386
Secondary	Phase 2 portion: Severe COVID-19 disease	Percentage of severe COVID-19 disease	Day 28 to 386
Secondary	Phase 3 portion: Severe COVID-19 disease	Percentage of severe COVID-19 disease	Day 28 to 386
Secondary	Phase 3 portion: COVID-19-related symptoms in virologically-confirmed cases	Percentage and intensity of COVID-19-related symptoms	through efficacy analysis, approximately 4 months
Secondary	Phase 3 portion: Laboratory-confirmed asymptomatic SARS-CoV-2 infection	Percentage of laboratory-confirmed asymptomatic SARS-CoV-2 infection: confirmed by the ELISA method for the N protein	Day 201
Secondary	Phase 3 portion: Laboratory-confirmed symptomatic SARS-CoV-2 infection	First occurence, in a subject, of laboratory-confirmed symptomatic SARS-CoV-2 infection: virologic method	through efficacy analysis, approximately 4 months
Secondary	Phase 3 portion: Laboratory-confirmed symptomatic SARS-CoV-2 infection	First occurence, in a subject, of laboratory-confirmed symptomatic SARS-CoV-2 infection: virologic method	Day 0 to 21
Secondary	Phase 3 portion: Laboratory-confirmed symptomatic SARS-CoV-2 infection	First occurence, in a subject, of laboratory-confirmed symptomatic SARS-CoV-2 infection: virologic method	Day 21 to 28
Secondary	Phase 3 portion: Viral shedding after SARS-CoV-2 infection	Duration and intensity of viral shedding after SARS-CoV-2 infection	through efficacy analysis, approximately 4 months
Secondary	Phase 3 portion: Laboratory-confirmed symptomatic SARS-CoV-2 infection (by strain)	First occurrence, in a subject, of laboratory-confirmed symptomatic SARS-CoV-2 infection by strain: virologic method	through efficacy analysis, approximately 4 months

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