This is a phase IIb/III, double-blind, randomised, active-controlled, multi-centre,non-inferiority clinical trial that aims to determine safety, tolerability andimmunogenicity of a booster vaccination with a recombinant protein receptor bindingdomain (RBD) fusion homodimer of XBB.1.16 adapted candidate against SARS-CoV-2 developedby 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.
Biological: PHH-1V81
booster of PHH-1V81
Biological: Comirnaty Omicron XBB1.5
booster of Comirnaty Omicron XBB1.5
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.
Hospital Germans Trias i Pujol
Badalona	3129028, Barcelona, Spain
Hospital HM Delfos
Barcelona	3128760, Barcelona, Spain
CAP Centelles
Centelles	3125442, Barcelona, Spain
Hospital Josep Trueta
Girona	3121456, Girona, Spain
Hospital HM Sanchinarro
Madrid	3117735, Madrid	3117732, Spain
Hospital Quironsalud Madrid
Madrid	3117735, Madrid	3117732, Spain
Hospital HM Puerta del Sur
Móstoles	3116025, Madrid	3117732, Spain
Hospital Regional de Málaga
Málaga	2514256, Málaga, Spain
Hospital Clínico Universitario de Valencia
Valencia	2509954, Valencia	2593113, Spain
Hospital de Cruces
Barakaldo	3109453, VIZCAYA, Spain
Teresa Prat, Study Director
 Hipra Scientific, S.L.U