COVID-19 Vaccine in Adults 18 Years of Age or Older

INTERVENTION: Product Name: Coronavirus‐Like Particle COVID‐19 Vaccine Pharmaceutical Form: Suspension for injection INN or Proposed INN: SARS‐COV‐2, VIRUS‐LIKE‐PARTICLES Current Sponsor code: CoVLP Other descriptive name: SARS‐CoV‐2, virus‐like‐particles Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 15‐ Pharmaceutical form of the placebo: Suspension for injection Route of administration of the placebo: Intramuscular use CONDITION: Covid‐19 ; MedDRA version: 23.1 Level: LLT Classification code 10084465 Term: COVID‐19 vaccination System Organ Class: 100000004865 Therapeutic area: Diseases [C] ‐ Respiratory Tract Diseases [C08] SECONDARY OUTCOME: Secondary end point(s): Phase 2 portion; In the Phase 2 portion, the secondary endpoints are:; Immunogenicity:; • Relative neutralizing antibody response between the healthy adults (Study Population #1) and the healthy elderly populations (Study Population #2; each age strata) induced at 21 days after the second vaccination will be analyzed using the following parameter: GMT;; • Relative neutralizing antibody response for the combination of healthy adults (Study Population #1) and healthy elderly adults (Study Population #2) compared to adults and elderly adults with significant comorbidities (Study Population #3) induced at 21 days after the second vaccination will be analyzed using the following parameter: GMT;; • Persistence of the Nab antibody response induced in each Study Population against the SARS‐CoV‐2 virus at Day 128, Day 201, and Day 386 will be analyzed using the following parameters: GMT, SC rate, and GMFR;; • Specific antibody response induced in each Study Population against the SARS‐CoV‐2 virus will be measured by the total IgG levels on Days 0, 21, and 42, and the persistence of these antibodies at Days 128, 201, and 386 and analyzed using the following parameters: GMT, SC rate, and GMFR;; • The ratio of neutralizing antibody titers: IgG (ELISA) antibody titers at Day 21, Day 42, Day 128, Day 201, and Day 386;; • Specific Th1 CMI response induced in each Study Population against the SARS‐CoV‐2 virus on Day 201 and Day 386, as measured by IFN‐? ELISpot;; • Specific T helper 2 (Th2) CMI response induced in each Study Population against the SARS‐CoV‐2 virus on Days 0, 21, 42, 201, and 386, as measured by IL‐4 ELISpot; ; Safety:; • Relative occurrence of solicited local and systemic AEs by intensity grades for seven days following each vaccine administration between the healthy adults (Study Population #1) and each healthy elderly population (Study Population #2);; • Relative occurrence of solicited local and systemic AEs by intensity grades for seven days following each vaccine administration for the combination of healthy adults (Study Population #1) and the healthy elderly adults (Study Population #2) compared to adults and elderly adults with significant comorbidities (Study Population #3);; • Occurrences of SAEs, MAAEs, AEs leading to withdrawal, AESIs (including VED), and deaths from Day 43 to Day 201;; • Occurrences of SAEs, MAAEs, AEs leading to withdrawal, AESIs (including VED), and deaths from Day 202 to Day 386.; Efficacy:; • First occurrence, in a subject, of laboratory‐confirmed (virologic method) symptomatic SARS‐CoV‐2 infection (= 7 days post‐second vaccination);; • Occurrences of severe COVID‐19 disease (= 7 days post‐second vaccination). Refer to the definition of severe COVID‐19 disease in the Secondary Objectives section above.; ; Phase 3 portion; In the Phase 3 portion, the secondary endpoints are:; Efficacy:; • Occurrences of laboratory‐confirmed (confirmed by the ELISA method for the N protein) asymptomatic SARSCoV‐2 infection starting 7 days after the second vaccination in Period 1 and prior to the cross‐over;; • Occurrences of severe COVID‐19 disease (= 7 days post‐second vaccination) in Period 1 and prior to crossover. Refer to the definition of severe COVID‐19 disease in the Secondary Objectives section above;; • Occurrence and intensity of COVID‐19‐related symptoms in virologically‐confirmed cases up until resolution of the symptoms in Period 1 compared to subjects administered the placebo and compared to subjects administered CoVLP at the time of cross‐over in Period 2;; • First occurrence, in a subject, of laboratory‐confirmed (virologic method) symptomatic SARS‐CoV‐2 infection (= first vaccination) in Period 1 and prior to cross‐over;; • First occurrence, in a subject, of laboratory‐confirmed (virologic method) symptomatic SARS‐CoV‐2 infection (= first vaccination and < second vaccination) in Period 1 and prior to cross‐over;; • First occurrence, in a subject, of laboratory‐confirmed (virologic method) symptomatic SARS‐CoV‐2 infection (= second vaccination and < 7 days post‐second vaccination) in Period 1 and prior to cross‐over;; • Occurrences of laboratory‐confirmed (confirmed by the ELISA method for the N protein) asymptomatic SARSCoV‐2 infection starting 7 days after the vaccination in Period 1 and prior to the cross‐over in subjects who only received a single vaccination;; • Duration and intensity of viral shedding after virologically‐confirmed SARS‐CoV‐2 infection in Period 1 and prior to cross‐over;; • First occurrence, in a subject, of laboratory‐confirmed (virologic method) symptomatic SARS‐CoV‐2 infection (= 7 days post‐second vaccination) in Period 1 by strain and prior to cross‐over;; Please, refer to protocol for further secondary endpoints (Immunogenicity and safety secondary endpoints in the Phase 3 portion).; Timepoint(s) of evaluation of this end point: as defined in the endpoints INCLUSION CRITERIA: Subjects must meet all of the following inclusion criteria at the Screening (Visit 1) and/or Vaccination (Visit 2) visits to be eligible for participation in this study; no protocol waivers are allowed. All Investigator assessment‐based judgements must be carefully and fully documented in the source documents: 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), study populations #1 and #2 must have a body mass index ( PRIMARY OUTCOME: Main Objective: Phase 3 portion; The primary objective of the Phase 3 portion of the study is:; Efficacy:; • To evaluate the efficacy of the CoVLP formulation, compared to placebo, in the prevention of laboratory confirmed symptomatic SARS‐CoV‐2 infection (virologic method) starting 7 days after the second vaccination in Period 1 and prior to the cross‐over. Primary end point(s): Phase 2 portion; In the Phase 2 portion, the primary endpoints are:; Safety:; • Occurrence, intensity, and relationship to vaccination of immediate AEs (30 minutes after each vaccination);; • Occurrence and intensity of solicited local and systemic AEs (for seven days following each vaccine administration);; • Occurrence, intensity, and relationship of unsolicited AEs for 21 days following each vaccine administration;; • Number and percentage of subjects with normal and abnormal clinically significant urine, haematological and biochemical values prior to and three days following each vaccination;; • Occurrences of SAEs, MAAEs, AEs leading to withdrawal, AESIs (including VED), and deaths up to 21 days following each vaccine administration;; Immunogenicity:; • Nab response induced in each Study Population against the SARS‐CoV‐2 virus on Days 0, 21, and 42 will be analyzed using the following parameter: geometric mean titers (GMT), seroconversion (SC) rate, and geometric mean fold rise (GMFR);; • Specific Th1 CMI response induced in each Study Population against the SARS‐CoV‐2 virus on Days 0, 21, and 42, as measured by IFN‐? ELISpot.; Phase 3 portion; In the Phase 3 portion, the primary endpoint is:; Efficacy:; • First occurrence, in a subject, of laboratory‐confirmed (virologic method) symptomatic SARS‐CoV‐2 infection (= 7 days post‐second vaccination) in Period 1 and prior to cross‐over. Secondary Objective: Phase 3 portion; The secondary objectives of the Phase 3 portion of the study are:; Efficacy:; • To evaluate the efficacy of the CoVLP formulation, compared to placebo, in the prevention of laboratory confirmed asymptomatic SARS‐CoV‐2 infection (serologic method) starting 7 days after the second vaccination in Period 1 and prior to the cross‐over;; • To evaluate the efficacy of the CoVLP formulation, compared to placebo, in the prevention of severe COVID‐19 disease starting 7 days after the second vaccination in Period 1 and prior to the cross‐over; ; Please refer the protocol for further details. ; Immunogenicity:; • To assess the immunogenicity of the CoVLP formulation, compared to placebo, in a subset of subjects, as determined by the protocol; Safety:; • To assess the safety and tolerability of the CoVLP formulation, compared to placebo, up to the end of the study. Timepoint(s) of evaluation of this end point: As defined in endpoints