Safety and Immunogenicity of a Booster Vaccination With an Adapted Vaccine

Phase IIb/III, Double-Blind, Randomised, Active-Controlled, Multi-Center, Non-Inferiority Clinical Trial, to Assess the Safety and Immunogenicity of a Booster Vaccination With an Adapted Recombinant Protein RBD Fusion Homodimer Candidate Against SARS-CoV-2, in Adults Vaccinated Against COVID-19

This is a phase IIb/III, double-blind, randomised, active-controlled, multi-centre, non-inferiority clinical trial that aims to determine safety, tolerability and immunogenicity of a booster vaccination with a recombinant protein receptor binding domain (RBD) fusion homodimer of XBB.1.16 adapted candidate against SARS-CoV-2 developed by HIPRA (PHH-1V81).

This is a phase IIb/III, double-blind, randomised, active-controlled, multi-centre, non-inferiority clinical trial that aims to determine safety, tolerability and immunogenicity of a booster vaccination with a recombinant protein receptor binding domain (RBD) fusion homodimer of XBB.1.16 adapted candidate against SARS-CoV-2 developed by HIPRA (PHH-1V81).

Approximately 612 participants who have received a primary scheme with an EU-approved mRNA vaccine (two doses) and at least one booster dose of an EU-approved mRNA vaccine against COVID-19, will be randomly assigned to the following two treatment arms in a PHH-1V81 : Comirnaty (Omicron XBB.1.5) 2:1 ratio:

• PHH-1V81 vaccine arm: Approximately 408 adults will receive a booster dose of PHH-1V81 (HIPRA adapted vaccine).
• Comirnaty vaccine arm: Approximately 204 adults will receive a booster dose of Comirnaty Omicron XBB.1.5.

Participants will be stratified before randomisation by age group (approximately 10% of adults ≥60 years old), and by number of doses previously received.

All participants will receive a booster dose of PHH-1V81 or Comirnaty Omicron XBB.1.5 at Day 0 and will be followed for 6 months. All subjects will be closely observed for 15 minutes after vaccination on site.

Inclusion Criteria:

• Adults aged 18 or older at Day 0
• Are willing and able to sign the informed consent and can comply with all study visits and procedures
• Participant must have received a primary scheme of an EU-approved mRNA vaccine (2 doses) and at least one booster dose with an EU-approved mRNA vaccine. Last booster dose must have been administered at least 6 months before Day 0.
• Having a negative Rapid Antigen Test for COVID-19 at Day 0 prior to vaccination.
• Adults determined by clinical assessment, including medical history and clinical judgement, to be eligible for the study, including adults with pre-existing chronic and stable diseases (non-immunocompromised), if these are stable and well-controlled according to the investigator's judgment.
• Uses an accepted method of contraception

Exclusion Criteria:

• Participant with an acute illness with fever ≥ 38.0°C at Day 0 or within 24 hours prior to vaccination. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator
• Participant with a medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behaviour that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Participant with history of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g. anaphylaxis) to any component of the study intervention
• Immunocompromised individuals defined as those with primary and secondary immune deficiencies and those receiving chemotherapy or immunosuppressant drugs other than steroids and glucocorticoids (maximum 30mg/day of prednisone, or equivalent, by any administration route for a maximum of 30 consecutive days), within 90 days prior to vaccination
• Participant with a bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection
• Have receipt of blood-derived immune globulins, blood, or blood-derived products in the past 3 months
• Participation in other studies involving study intervention if last dose is within 28 days prior to screening and/or it is planned to receive during study participation
• Received any non-study vaccine within 14 days before or after screening. For live or attenuated vaccines, 4 weeks before or after screening
• Received any COVID-19 vaccines other than EU-approved mRNA vaccines
• Received any Omicron XBB adapted vaccine before Day 0
• COVID-19 infection diagnosed in the previous 6 months before Day 0. History of COVID-19 infections is allowed
• History of a diagnosis or other conditions that, in the judgment of the investigator, may affect study endpoint assessment or compromise participant safety.