Study of Recombinant Protein Vaccines with Adjuvant as a Primary Series and as a Booster Dose against COVID-19 in Adults 18 Years of Age and Older

INTERVENTION: Product Name: Monovalent CoV2 preS dTM‐AS03 COVID‐19 vaccine Product Code: 549 Pharmaceutical Form: Emulsion for injection INN or Proposed INN: Not Applicable Current Sponsor code: 549 Other descriptive name: SARS‐CoV‐2 prefusion Spike delta TM protein, recombinant Concentration unit: µg/ml microgram(s)/millilitre Concentration type: not less then Concentration number: 5‐ Product Name: Monovalent CoV2 preS dTM‐AS03 COVID‐19 vaccine Product Code: 549 Pharmaceutical Form: Emulsion for injection INN or Proposed INN: Not Applicable Current Sponsor code: 549 Other descriptive name: SARS‐CoV‐2 prefusion Spike delta TM protein, recombinant Concentration unit: µg/ml microgram(s)/millilitre Concentration type: not less then Concentration number: 10‐ CONDITION: COVID‐19 ; MedDRA version: 23.0 Level: PT Classification code 10084268 Term: COVID‐19 System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: ‐To assess the safety profile of the study vaccines in each study intervention group.; ‐To assess the neutralizing antibody profile after primary series vaccination in SARS‐CoV‐2‐naïve adults.; ‐To demonstrate that a booster dose of monovalent or bivalent SARS‐CoV‐2 vaccine given to adults previously vaccinated with an authorized/approved COVID‐19 vaccine induces an immune response that is non‐inferior to the response induced by a two‐dose priming series with the monovalent vaccine, and superior to that observed immediately before booster.; ‐To demonstrate that two doses of monovalent (B.1.351)‐AS03 or bivalent (D614 + B.1.351)‐AS03 SARS‐CoV‐2 vaccine induces an immune response that is non inferior to the response induced by monovalent (D614)‐AS03 vaccine Primary end point(s): 1‐Presence of immediate adverse events : Immediate adverse events include unsolicited adverse events occurring ; within 30 minutes after injection; 2‐Presence of solicited injection site or systemic reactions : Injection site reactions: injection site pain, erythema and swelling. Systemic ; reactions: fever, headache, malaise and myalgia.; 3‐Presence of unsolicited adverse events : Adverse events other than solicited reactions; 4‐Presence of serious adverse events : Serious adverse events are reported throughout the study; 5‐Presence of adverse events of special interest : Adverse events of special interest are reported throughout the study. ; 6‐Presence of medically‐attended adverse events : Medically‐attended adverse events are new onset or a worsening of a condition that prompts the participant or participant's parent/guardian to seek unplanned medical advice at a physician's office or Emergency Department.; 7‐Neutralizing antibody titer at Day 1 : Neutralizing antibody titers are expressed as geometric mean titers; 8‐Neutralizing antibody titer at Day 36 : Neutralizing antibody titers are expressed as geometric mean titers.; 9‐Neutralizing antibody titer fold‐rise post vaccination : Neutralizing antibody titer fold‐rise post‐vaccination.; 10‐ 2‐fold rise and 4‐fold‐rise in neutralization antibody titer : Fold‐rise in antibody neutralization titer post‐vaccination relative to Day 1. ; 11‐Responders, as determined by neutralizing antibody titers at Day 36 : Responders, defined as participants who had baseline values below lower limit of quantification (LLOQ) with detectable neutralization titer above assay LLOQ at each pre‐defined time point and participants with baseline values above LLOQ with a 4‐fold increase in neutralizing antibody titer at Day 36; 12‐Neutralizing antibody titer at Day 1 (pre‐booster injection): Neutralizing antibody titers are expressed as geometric mean titers.; 13‐Neutralizing antibody titer at Day 15 (post booster injection) : Neutralizing antibody titers are expressed as geometric mean titers.; 14‐Neutralizing antibody titer at Day 36 (Cohorts 1 and 2 Comparator Group and all Cohort 3 arms) : Neutralizing antibody titers are expressed as geometric mean titers.; 15‐Responders, as determined by neutralizing antibody titers at Day 36 (Cohorts 1 and 2 Comparator Group and all Cohort 3 arms) : Responders are defined as participants with a 4‐fold‐or greater rise in serum neutralization titer [pre/post] at Day 36 relative to Day 1 Secondary Objective: ‐To assess the neutralizing and binding antibody profiles after primary series vaccination at pre‐defined time points during the study. ; ‐To assess the neutralizing and binding antibody responses of booster vaccination. ; ‐To describe the occurrences of laboratory‐confirmed symptomatic COVID‐19 after primary series and booster vaccination.; ‐To describe the occurrences of serologically‐confirmed SARS‐CoV‐2 infection after primary series vaccination. Timepoint(s) of evaluation of this end point: 1:Within 30 minutes after vaccination; 2:Within 7 days after vaccination; 3:Within 21 days after vaccination; 4/5/6:From Day 1 to Day 387; 7:Day 1; 8:Day 36; 9/10/11:From Day 1 to Day 36; 12:Day 1 (pre‐booster injection); 13:Day 15 (post‐booster injection); 14:Day 36; 15:From Day 1 to Day 36 SECONDARY OUTCOME: Secondary end point(s): 1.Neutralizing antibody titer at all pre‐defined time points ; 2.Neutralizing antibody titer fold‐rise post‐vaccination at all pre‐defined time points : Fold‐rise in antibody neutralization titer post‐vaccination relative to Day 1.; 3. 2‐fold rise and 4‐fold‐rise in neutralization antibody titer at all pre‐defined time points : Fold‐rise in antibody neutralization titer post‐vaccination relative to Day 1.; 4.Responders, as determined by neutralizing antibody titers at each pre‐defined time point : Responders, defined as participants who had baseline values below LLOQ with detectable neutralization titer above assay LLOQ at each pre‐defined time point and participants with baseline values above LLOQ with a 4‐fold increase in neutralizing antibody titer at each pre‐defined timepoint.; 5.Binding antibody concentrations; 6.Binding antibody fold‐rise : Fold‐rise in concentration relative to Day 1. ; 7.2‐fold‐rise and 4‐fold rise in binding antibody concentration : Fold‐rise in concentration relative to Day 1. ; 8.Responders, as determined by binding antibody concentrations : Responders are defined as participants who had baseline values below LLOQ with detectable anti concentration above assay LLOQ at each predefined time point and participants with baseline values above LLOQ with a 4‐fold increase in anti‐S antibody concentration at each pre‐defined time point.; 9.Occurrences of laboratory‐confirmed symptomatic COVID‐19 : Symptomatic COVID‐19 is defined as laboratory‐confirmed SARS‐CoV‐2 infection accompanied by protocol‐defined COVID‐19‐like illness. Laboratory‐confirmed SARS‐CoV‐2 infection is defined as a positive result for SARS CoV‐2 by nucleic acid amplification test (NAAT), done by the central laboratory or locally, on at least one respiratory sample.; 10.Occurrences of symptomatic COVID‐19 episodes associated with hospitalization : Symptomatic COVID‐19 is defined as laboratory‐confirmed SARS‐CoV‐2 infection accompanied by protocol‐defined COVID‐19‐like illness.; 11.Occurrences of severe symptomatic COVID‐19 : Symptomatic COVID‐19 is defined as laboratory‐confirmed SARS‐CoV‐2 infection accompanied by protocol‐defined COVID‐19‐like illness with pre‐defined criteria of severity.; 12.Occurrences of death associated with symptomatic COVID‐19 : Symptomatic COVID‐19 is defined as laboratory‐confirmed SARS‐CoV‐2 infection accompanied by protocol‐defined COVID‐19‐like illness.; 13.Occurrences of serologically‐confirmed SARS CoV‐2 infection : Serologically‐confirmed SARS‐CoV‐2 infection is defined as a positive result in a serum sample for antibodies against SARS‐CoV‐2.; 14.Neutralizing antibody titer at all pre‐defined time points post‐booster and booster comparator injection ; 15.Neutralizing antibody titer fold‐rise post‐vaccination at all pre‐defined time points postbooster and booster comparator injection : Neutralizing antibody titer fold‐rise post‐vaccination.; 16. 2‐fold rise and 4‐fold‐rise in neutralization antibody titer at all pre‐defined time points postbooster and booster comparator injection : Neutralizing antibody titer fold‐rise post‐vaccination.; 17.Seroresponse rate post‐booster and booster comparator injection : Seroresponse rate is defined as the percentage or participants with 4‐fold‐or greater rise in serum neutralization titer [pre/post] at post‐vaccination relative to pre‐vaccination. ; 18.Binding antibody concentrations post‐booster injection ; 19.Binding antibody fold‐rise post‐booster injection : Fold‐rise in concentration relative to Day 1. ; 20. 2‐fold‐rise and 4‐fold rise in binding antibody concentration post‐booster injection : Fold‐rise in concentration relative to Day 1. Timepoint(s) of evaluation of this end point: 1/2/3/4/5/6/7/8:Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387; 9/10/11/12/13:From Day 1 to Day 38; 14/15/16/17:Day 1 and Day 15 (post‐booster injection) and Day 36; 18/19/20:Day 1, Day 15, Day 29, Day 91, Day 181, and Day 366 (post‐booster injection) INCLUSION CRITERIA: ‐Aged 18 years or older on the day of inclusion. ‐A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: Is of non‐childbearing potential. To be considered of non‐childbearing potential, a female must be post‐menopausal for at least 1 year or surgically sterile. OR Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to the first vaccination until at least 12 weeks after the second vaccination. A participant of childbearing potential must have a negative highlysensitive pregnancy test (urine or serum as required by local regulation) within 4 hours before any dose of study intervention. ‐Informed consent form has been signed and dated. ‐Able to attend all scheduled visits and to comply with all study procedures. ‐SARS‐CoV‐2 rapid serodiagnostic test performed at the time of enrollment to detect presence