Immunogenicity and Safety of a Booster Vaccination With a Recombinant Protein RBD Candidate Vaccine Against SARS-CoV-2 in Healthy Adults Volunteers Fully Vaccinated Followed by an Extension Period to Study a Fourth Dose Administration.

NCT05142553 | Completed Phase 2 DMC

• 1 other identifier: HIPRA-HH-2
• Study Type: interventional
• Target: 887
• Locations: 1 country
• Sites: 10

Brief Summary

This Phase IIb clinical study aims to compare the immunogenicity and safety of a booster dose of recombinant protein RBD fusion dimer vaccine as a heterologous booster (to subjects who have received the second dose of the Pfizer-BioNTech (Comirnaty) COVID-19 vaccine at least 182 days prior to the booster dose in this study) versus a homologous booster (subjects who received the second dose of the Comirnaty COVID-19 vaccine at least 182 days prior to the booster dose in this study) will receive a third dose of the Comirnaty vaccine). The extension part of the study aims to compare the immunogenicity and safety of a fourth dose of PHH-1V in subjects with a primovaccination with Pfizer-BioNTech (Comirnaty) COVID-19 vaccine plus either a booster dose of Comirnaty or PHH-1V versus those with three vaccinations of Comirnaty.

Conditions

SARS-CoV-2 Acute Respiratory Disease; COVID-19

Outcome Measures

Primary Outcomes (6)

• Part A: Changes of the immunogenicity against Wuhan

  Neutralisation titre measured as inhibitory concentration 50 (IC50) for each individual sample and geometric mean titre (GMT) for treatment group comparison at Baseline and Day 14.

  14 days

• Safety and tolerability of PHH-1V as third or fourth dose

  Number, percentage, and characteristics of solicited local reactions through Day 7 after vaccination.

  7 days

• Safety and tolerability of PHH-1V as third or fourth dose

  Number, percentage, and characteristics of unsolicited local and systemic adverse events (AEs) through Day 28 after vaccination.

  28 days

• Safety and tolerability of PHH-1V as third or fourth dose

  Number and percentage of serious adverse events (SAEs), adverse event of special interest (AESI) and medically attended adverse events (MAAE) through Day 364.

  364 days

• Safety and tolerability of PHH-1V as third or fourth dose

  Change from baseline in safety laboratory parameters at Days 14, 28, 182, and 364 after vaccination.

  Days 14, 28, 182, and 364

• Part B: Changes of the immunogenicity against Omicron BA.1

  Neutralisation titre measured as inhibitory concentration 50 (IC50) by PBNA and reported as log10 concentration for each individual sample and GMT, at Day 14 post-dose 4 of PHH-1V in cohort 2 versus post-dose 3 in cohort 2 (cohort 2 having three doses of Comirnaty + the frouth dose of PHH-1V).

  Day 14

Secondary Outcomes (8)

• Changes of the immunogenicity against the Variants of Concern (VOC)

  Day 14, 28, 98, 182, 364

• Changes of the immunogenicity against the Variants of Concern (VOC)

  Day 14, 28, 98, 182 and 364

• Changes of the immunogenicity against the Variants of Concern (VOC)

  Day 14, 28, 98, 182 and 364

• Changes of the immunogenicity against the Variants of Concern (VOC)

  Day 14, 28, 98, 182 and 364

• Changes in immunogenicity at Baseline and Days 14, 28, 182 &364.

  Days 14, 28, 98, 182 and 364

Other Outcomes (5)

• Number of subjects with SARS-CoV-2 infections in subjects without evidence of infection before study's participation.

  364 Days

• Number of COVID-19 severe infections after receiving PHH-1V.

  through Day 364.

• Number of COVID-19 severe infections after receiving PHH-1V.

  through Day 364.

Study Arms (2)

COVID-19 Vaccine HIPRA

EXPERIMENTAL

40 ug/0.5 ml

Biological: COVID-19 Vaccine HIPRA

Cominarty (Pfizer-BioNtech)

ACTIVE COMPARATOR

30 micrograms/dose concentrate for dispersion for injection

Biological: Cominarty (Pfizer-BioNtech)

Interventions

COVID-19 Vaccine HIPRA BIOLOGICAL

Subjects will receive one injection of COVID-19 Vaccine HIPRA

COVID-19 Vaccine HIPRA

Cominarty (Pfizer-BioNtech) BIOLOGICAL

Subjects will receive one injection of Cominarty Vaccine

Cominarty (Pfizer-BioNtech)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, by birth, ≥ 18 years old at Screening.
• Willing and able to comply with scheduled visits, laboratory tests, complete diaries, and other study procedures.
• Body Mass Index (BMI) between 18 to 40 kg/m2.
• Has received a complete COVID-19 vaccination programme (two administrations, prime and boosting) at least 182 days and with a maximum of 365 days before Screening with Comirnaty vaccine.
• Has a negative COVID-19 polymerase chain reaction (PCR) test at Screening.
• Willing to avoid all other vaccines within 4 weeks before and after vaccination in this study (Day 0). Seasonal influenza vaccination is allowed if it is received at least 14 days before or after vaccination.
• Willing to refrain from blood donation during the study.
• Women of childbearing potential must have a negative urine pregnancy test at Screening and prior to vaccination.
• Women of childbearing potential must be willing to use highly effective contraceptive methods or have practiced sexual abstinence from the screening visit until 8 weeks after the vaccination.
• Males who are not sterilised, must be willing to avoid impregnating female partners from Screening until 8 weeks after vaccination.
• Willing and able to provide written informed consent prior the initiation of any study procedures.

You may not qualify if:

• Pregnant or lactating or intending to become pregnant or plans to breastfeed during the study.
• Positive pregnancy test at Screening or vaccination day.
• Any medical disease (acute, subacute, intermittent, or chronic) or condition that in the opinion of the Investigator compromises the subject's safety, preclude vaccination or compromises interpretation of the results.
• Ongoing serious psychiatric condition likely to affect participation in the study (e.g., ongoing severe depression, recent suicidal ideation, bipolar disorder, personality disorder, alcohol and drug dependency, severe eating disorder, psychosis, use of mood stabilisers or antipsychotic medication).
• History of respiratory disease (e.g., chronic obstructive pulmonary disease \[COPD\]) requiring daily medications currently or any treatment of respiratory disease exacerbations (e.g., asthma exacerbation) in the last 6 months.
• History of significant cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease) or history of myocarditis or pericarditis as an adult. Controlled hypertension will be permitted at the discretion of the Investigator.
• History of neurological or neurodevelopmental conditions (e.g., epilepsy, stroke, seizures in the last 3 years, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome, encephalomyelitis, or transverse myelitis).
• Ongoing malignancy or recent diagnosis of malignancy in the last five years excluding basal cell and squamous cell carcinoma of the skin, which are allowed.
• Any confirmed or suspected autoimmune, immunosuppressive or immunodeficiency disease/condition (iatrogenic or congenital), including human immunodeficiency virus (HIV) infection, asplenia, or recurrent severe infections.
• Acute illness within 72 hours before vaccination day that, in the opinion of the Investigator may interfere the evaluation of safety parameters.
• Received investigational drug within 90 days before Screening or plans to participate in another interventional clinical study (drug/biologic/device) within 12 months after vaccination.
• History of hypersensitivity or severe allergic reactions, including anaphylaxis, generalised urticarial, angioedema and other significant reactions related to food, drugs, vaccines, or pharmaceutical agents, which are likely to be exacerbated by any component of the COVID-19 vaccine HIPRA.
• Use of any immunosuppressant, glucocorticoids, or other immune-modifying drugs within 2 months before vaccination day; or anticipation of the need for immunosuppressive treatment within 182 days after vaccination.
• Received immunoglobulin, blood-derived products, or other immunosuppressant drugs within 90 days before vaccination (Day 0).
• Known disturbance of coagulation (iatrogenic or congenital) or blood dyscrasias.

Sponsors & Collaborators

• Hipra Scientific, S.L.U: lead
• Laboratorios Hipra, S.A.: collaborator

Study Sites (10)

Hospital Germans Trias I Pujol

Badalona, BARCELONA, 08916, Spain

Location

Hospital Vall Hebron

Barcelona, BARCELONA, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Barcelona, 17170, Spain

Location

Hospital Universitari Dr. Josep Trueta

Girona, Girona, 17007, Spain

Location

Hospital Gregorio Marañón

Madrid, Madrid, 28007, Spain

Location

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

Location

Hospital Principe de Asturias

Meco, Madrid, 28805, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, Málaga, 29010, Spain

Location

Hospital Clínico de Valencia

Valencia, Valencia, 46010, Spain

Location

Hospital de Cruces

Barakaldo, VIZCAYA, 48903, Spain

Location

Related Publications (3)

• Corominas J, Garriga C, Prenafeta A, Moros A, Canete M, Barreiro A, Gonzalez-Gonzalez L, Madrenas L, Guell I, Clotet B, Izquierdo-Useros N, Raich-Regue D, Gallemi M, Blanco J, Pradenas E, Trinite B, G Prado J, Perez-Caballero R, Bernad L, Plana M, Esteban I, Aurrecoechea E, Taleb RA, McSkimming P, Soriano A, Nava J, Anagua JO, Ramos R, Marti Lluch R, Corpes Comes A, Otero Romero S, Martinez-Gomez X, Camacho-Arteaga L, Molto J, Benet S, Bailon L, Arribas JR, Borobia AM, Queiruga Parada J, Navarro-Perez J, Forner Giner MJ, Lucas RO, Vazquez Jimenez MDM, Lopez Fernandez MJ, Alvarez-Mon M, Troncoso D, Arana-Arri E, Meijide S, Imaz-Ayo N, Garcia PM, de la Villa S, Rodriguez Fernandez S, Prat T, Torroella E, Ferrer L. Humoral and cellular immune responses after 6 months of a heterologous SARS-CoV-2 booster with the protein-based PHH-1V vaccine in a phase IIb trial. Vaccine. 2025 Feb 15;47:126685. doi: 10.1016/j.vaccine.2024.126685. Epub 2025 Jan 13.

  PMID: 39809095 DERIVED

• Moros A, Prenafeta A, Barreiro A, Perozo E, Fernandez A, Canete M, Gonzalez L, Garriga C, Pradenas E, Marfil S, Blanco J, Cebollada Rica P, Sistere-Oro M, Meyerhans A, Prat Cabanas T, March R, Ferrer L. Immunogenicity and safety in pigs of PHH-1V, a SARS-CoV-2 RBD fusion heterodimer vaccine candidate. Vaccine. 2023 Aug 7;41(35):5072-5078. doi: 10.1016/j.vaccine.2023.07.008. Epub 2023 Jul 16.

  PMID: 37460353 DERIVED

• Corominas J, Garriga C, Prenafeta A, Moros A, Canete M, Barreiro A, Gonzalez-Gonzalez L, Madrenas L, Guell I, Clotet B, Izquierdo-Useros N, Raich-Regue D, Gallemi M, Blanco J, Pradenas E, Trinite B, Prado JG, Blanch-Lombarte O, Perez-Caballero R, Plana M, Esteban I, Pastor-Quinones C, Nunez-Costa X, Taleb RA, McSkimming P, Soriano A, Nava J, Anagua JO, Ramos R, Lluch RM, Comes AC, Romero SO, Gomez XM, Sans-Pola C, Molto J, Benet S, Bailon L, Arribas JR, Borobia AM, Parada JQ, Navarro-Perez J, Forner Giner MJ, Lucas RO, Jimenez MDMV, Compan SO, Alvarez-Mon M, Troncoso D, Arana-Arri E, Meijide S, Imaz-Ayo N, Garcia PM, de la Villa Martinez S, Fernandez SR, Prat T, Torroella E, Ferrer L. Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial. Lancet Reg Health Eur. 2023 May;28:100613. doi: 10.1016/j.lanepe.2023.100613. Epub 2023 Apr 14.

  PMID: 37131861 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

HIPRA COVID-19 vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Teresa Prat

  HIPRA SCIENTIFIC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Subjects and the clinical study team will remain blinded to treatment allocation. Clinical staff involved in study drug preparation and administration will be aware of which vaccine the subject is receiving. The extension of the fourth dose will be unblinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase IIb, randomised, double-blind, active-controlled, multicentre, noninferiority clinical study that aims to determine immunogenicity, reactogenicity, safety, and tolerability of a booster vaccination of test vaccine followed by an extension period to study a fourth dose administration of the vaccine.

Study Record Dates

• First Submitted: November 17, 2021
• First Posted: December 2, 2021
• Study Start: November 16, 2021
• Primary Completion: May 29, 2023
• Study Completion: May 29, 2023
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (10)