A Phase IIb, Double-blind, Randomised, Active-controlled, Multi-centre, Non-inferiority Trial Followed by a Phase III, Single-arm, Open-label Trial, to Assess Immunogenicity and Safety of a Booster Vaccination With a Recombinant Protein RBD Fusion Dimer Candidate (PHH-1V) Against the Virus That Cause COVID-19, Know as Severe Acute Respiratoy Syndrome Coronavirus 2 (SARS-CoV-2)SARS-CoV-2, in Adults Fully Vaccinated Against COVID-19 Followed by an Extension Period to Study a Fourth Dose Administration of PHH-1V.
Overview
- Phase
- Phase 2
- Intervention
- COVID-19 Vaccine HIPRA
- Conditions
- COVID-19
- Sponsor
- Hipra Scientific, S.L.U
- Enrollment
- 887
- Locations
- 10
- Primary Endpoint
- Safety and tolerability of PHH-1V as third or fourth dose
- Status
- Completed
- Last Updated
- last month
Overview
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.
Detailed Description
The study population includes 1075 healthy adults aged above 18 years old who have received two doses of the Comirnaty vaccine, and are at least 182 days and less than 365 days after their second dose will be randomly assigned to two treatment arms. In each arm, volunteers will be randomized in a ratio Test vaccine:Comirnaty of 2:1. Each participant will receive one booster immunisation and will be followed for 1 year to evaluate immunogenicity response and assess the safety of the test vaccine in comparison to Cominarty. The study population of the extension part includes 200 healthy adults abode 18 years old who have received or: 3 doses of Comirnaty vaccine, or 2 doses of Comirnaty + 1 dose of PHH-1V. Each participant will receive one dose of PHH-1V.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Part A: Inclusion Criteria:
- •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/m
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
COVID-19 Vaccine HIPRA
40 ug/0.5 ml
Intervention: COVID-19 Vaccine HIPRA
Cominarty (Pfizer-BioNtech)
30 micrograms/dose concentrate for dispersion for injection
Intervention: Cominarty (Pfizer-BioNtech)
Outcomes
Primary Outcomes
Safety and tolerability of PHH-1V as third or fourth dose
Time Frame: Days 14, 28, 182, and 364
Change from baseline in safety laboratory parameters at Days 14, 28, 182, and 364 after vaccination.
Part A: Changes of the immunogenicity against Wuhan
Time Frame: 14 days
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.
Part B: Changes of the immunogenicity against Omicron BA.1
Time Frame: Day 14
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).
Safety and tolerability of PHH-1V as third or fourth dose
Time Frame: 7 days
Number, percentage, and characteristics of solicited local reactions through Day 7 after vaccination.
Safety and tolerability of PHH-1V as third or fourth dose
Time Frame: 28 days
Number, percentage, and characteristics of unsolicited local and systemic adverse events (AEs) through Day 28 after vaccination.
Safety and tolerability of PHH-1V as third or fourth dose
Time Frame: 364 days
Number and percentage of serious adverse events (SAEs), adverse event of special interest (AESI) and medically attended adverse events (MAAE) through Day 364.
Secondary Outcomes
- Immunogenicity to the SARS-CoV-2 spike glycoprotein(Days 14, 28, 98, 182, and 364)
- T-cell mediated responses against the SARS-CoV-2 S glycoprotein at Baseline & D14.(Day 14)
- Th-1/Th-2 T-cell mediated responses against the SARS-CoV-2 S glycoprotein at Baseline & D14. Th-1/Th2(Day 14)
- Changes in immunogenicity at Baseline and Days 14, 28, 182 &364.(Days 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, 364)