Study of Monovalent and Bivalent Recombinant Protein Vaccines Against COVID-19 in Adults 18 Years of Age and Older

A Parallel-group, Phase III, Multi-stage, Modified Double-blind, Multi-armed Study to Assess the Efficacy, Safety, and Immunogenicity of Two SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (Monovalent and Bivalent) for Prevention Against COVID-19 in Adults 18 Years of Age and Older as a Primary Series and Open-label Extension to Assess Immunogenicity, Safety, Efficacy of a Monovalent Booster Dose of SARS-CoV2 Adjuvanted Recombinant Protein Vaccine

The purpose of this Phase III study is to assess the efficacy, safety, and immunogenicity of two CoV2 preS dTM-AS03 vaccines (monovalent and bivalent) as part of primary series vaccinations in a multi-stage approach, as well as a booster injection of a CoV2 preS dTM-AS03 vaccine, in adults 18 years of age and older.

A total of approximately 21 046 participants are planned to be enrolled (5080 per study intervention group in Stage 1 and 5443 per study intervention group in Stage 2).

Initial, double-blind, primary series study design is planned for 365 days post-last Initial injection (ie, approximately 386 days total) for each participant.

Based on decisions of the Study Oversight Group, Stage 1 and Stage 2 participants will be invited to participate in an unblinded Crossover / Booster study design with duration as follows:

• For participants who initially received vaccine: 12 months post-booster (ie, approximately 18 to 24 months)
• For participants who initially received placebo: ≥ 4 months post-last dose of the primary series + 12 months post-booster (ie, approximately 28 to 34 months)
• For participants who do not consent to continue in the unblinded Crossover / Booster part of the study, all study procedures will be stopped and participants will be discontinued from the study.

The duration of participation in the initial, double-blind, primary series design of the study will be approximately 365 days post-last injection (ie, approximately 386 days total) for each participant.

Based on decisions of the Study OG, Stage 1 and Stage 2 participants will be invited to participate in an unblinded Crossover / Booster study design with duration as follows:

• For participants who initially received vaccine: 12 months post-booster (ie, approximately 18 to 24 months)
• For participants who initially received placebo: ≥ 4 months post-last dose of the primary series + 12 months post-booster (ie, approximately 28 to 34 months)
• For participants who do not consent to continue in the unblinded Crossover / Booster part of the study, all study procedures will be stopped and participants will be discontinued from the study.

Inclusion Criteria:

• Aged 18 years or older on the day of inclusion.

• For persons living with human immunodeficiency virus (HIV), stable HIV infection determined by participant currently on antiretrovirals with CD4 count > 200/mm3.

• SARS-CoV-2 rapid serodiagnostic test performed at the time of enrollment to detect presence of SARS-CoV-2 antibodies.

• Does not intend to receive an authorized/approved COVID-19 vaccine despite encouragement by the Investigator to receive the authorized vaccine available to them at the time of enrollment.

• Informed consent form has been signed and dated

• Able to attend all visits and to comply with all study procedures

• Covered by health insurance, only if required by local, regional or national regulations

• 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 study intervention administration until at least 12 weeks after the second study intervention administration.

A participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 25 hours before any dose of study intervention.

Exclusion Criteria:

• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to a vaccine containing any of the same substances.
• Dementia or any other cognitive condition at a stage that could interfere with following the study procedures based on Investigator?s judgment.
• Self-reported thrombocytopenia, contraindicating intramuscular (IM) vaccination based on Investigator?s judgment
• Bleeding disorder, or receipt of anticoagulants in the past 21 days preceding inclusion, contraindicating IM vaccination based on Investigator?s judgment.
• Unstable acute or chronic illness that in the opinion of the Investigator or designee poses additional risk as a result of participation or that could interfere with the study procedures.
• Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ? 38.0 C [? 100.4 F]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
• Receipt of any vaccine in the 30 days preceding or on the day of the first study vaccination or planned receipt of any vaccine between the first study vaccination and in the 30 days following the second study vaccination except for influenza vaccination, which may be received at any time in relation to study intervention.
• Prior administration of a coronavirus vaccine (SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome).
• Receipt of solid-organ or bone marrow transplants in the past 180 days.
• Receipt of anti-cancer chemotherapy in the last 90 days.
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
• Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.
• Participation at the time of study enrollment (or in the 30 days preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure.