Safety and Immunogenicity of Recombinant Protein RBD Fusion Dimer Vaccine Against the Virus That Cause COVID-19, Known as Severe Acute Respiratoy Syndrome Coronavirus 2 (SARS-CoV-2)

A Phase IIb Study to Evaluate Safety and Immunogenicity of Recombinant Protein RBD Fusion Dimer Candidate Vaccine Against the Virus That Cause COVID-19, Known as Severe Acute Respiratoy Syndrome Coronavirus 2 (SARS-CoV-2) in Adult Healthy Volunteers

This is a Phase IIb, randomized, controlled, observer-blinded, clinical trial to evaluate safety and immunogenicity of COVID-19 Vaccine HIPRA in adult healthy volunteers in Vietnam

Study Overview

• Status: Completed
• Conditions: COVID-19; SARS-CoV-2 Acute Respiratory Disease
• Intervention / Treatment: Biological: COVID-19 Vaccine HIPRA; Biological: Cominarty (Pfizer-BioNtech)

Detailed Description

The study population includes 256 healthy adults aged 18-60 which will be randomized in a ratio 1:1 test:commercial vaccine. Each participant will receive 2 immunisations separated by 21 days and will be followed for 24 weeks after the second dose.

• Study Type: Interventional
• Enrollment (Actual): 629
• Phase: Phase 2

Contacts and Locations

Study Locations

• Vietnam
  • Hanoi, Vietnam
    • National Institute of Hygiene and Epidemiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults males or females between 18-60 years of age at the day of screening.
• Willing and able to comply with scheduled visits, laboratory test, complete diaries and other study procedures.
• Body Mass Index 18 to 40 Kg/m2 at screening.
• COVID19 negative quick test or PCR test and negative serum IgG binding antibody response to the SARS-CoV-2 S glycoprotein at screening or prior the first vaccination. If an enrolled subject has neutralizing antibodies at baseline, he or she will be excluded from final analysis.
• Willing to avoid all other vaccines within 4 weeks before and after each injection. Seasonal influenza vaccination is allowed if it is received at least 14 days before or after the vaccination.
• Women of childbearing potential must have a negative pregnancy test in urine before the inclusion of the study and prior to each vaccination.
• If female of childbearing potential, willing to use highly effective contraceptive methods or have practiced sexual abstinence from the screening visit until 8 weeks after the last injection.
• If male and not sterilized, willing to avoid impregnating female partners from screening until 8 weeks after last injection.
• Willing and able to provide written informed consent prior the initiation of any study procedures.

Exclusion Criteria:

• Pregnant or lactating or intending to become pregnant or plans to breastfeed during the study.
• Positive pregnancy test at screening or prior to each vaccination.
• Any medical disease (acute, subacute, intermittent or chronic) or condition with grade 2 or above that in the opinion of the investigator compromise the volunteer's safety, preclude vaccination or compromise interpretation of the results.
• History of serious psychiatric condition likely to affect participation in the study.
• History of respiratory disease (e.g., chronic obstructive pulmonary disease (COPD) and asthma) requiring any daily medications currently or any treatment of respiratory disease exacerbations (e.g., asthma exacerbation) in the last 5 years.
• History of significant cardiovascular disease including hypertension (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease) or history of myocarditis or pericarditis as an adult.
• History of neurological or neurodevelopmental conditions (e.g., migraines, 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 immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent severe infections.
• Any autoimmune or immunodeficiency disease/condition (iatrogenic or congenital).
• Acute illness within 72 hours prior each vaccination that in the opinion of the investigator may interfere the evaluation of safety parameters.
• Usage of any investigational drug ≤ 90 days prior to study entry or plan to participate in another research involving an investigational product (drug/biologic/device) within 12 months after the first study vaccination.
• History of hypersensitivity or severe allergic reaction including anaphylaxis, generalized urticarial, angioedema and other significant reactions related to food, drugs, vaccines or pharmaceutical agents.
• History of allergic disease or reactions 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 prior to first study vaccination; or anticipation of the need for immunosuppressive treatment within 6 months after last vaccination.
• Received immunoglobulin, blood-derived products, or other immunosuppressant drugs within 90 days prior to first study vaccination.
• Known disturbance of coagulation (iatrogenic or congenital) or blood dyscrasias.
• Known bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture.
• Chronic liver disease
• Positive test for HIV types 1 or 2 infection, hepatitis B surface antigen (HBsAg), or hepatitis C virus antibodies (HCV Abs) at screening
• Suspected or known current alcohol abuse or any other substances abuse (except tobacco).
• History of COVID-19 infection.
• Receipt of medications intended to prevent COVID-19.
• Ever received an experimental vaccine against COVID-19.
• Close contact of anyone known to have SARS-CoV-2 infection within 15 days prior to screening visit.
• Being directly involved in the conduct of the study
• Any condition and/or laboratory finding that at the investigator consideration would interfere with the study or put at risk the participant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: COVID-19 Vaccine HIPRA; Subjects will receive 2 injections of COVID-19 vaccine HIPRA administered 21 days apart.	Biological: COVID-19 Vaccine HIPRA; Subjects will receive 2 injections of COVID-19 vaccine HIPRA administered 21 days apart
Active Comparator: Commercial COVID-19 Vaccine; Subjects will receive 2 injections of COVID-19 vaccine HIPRA administered 21 days apart	Biological: Cominarty (Pfizer-BioNtech); Subjects will receive 2 injections of Cominarty administered 21 days apart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of COVID-19 HIPRA vaccine in healthy adult volunteers	Number and percentage of solicited local and systemic reactogenicity adverse events for 7 days following each vaccination.	7 days
Safety and tolerability of COVID-19 HIPRA vaccine in healthy adult volunteers	Number and percentage of unsolicited local and systemic reactogenicity adverse events for 28 days following each vaccination.	28 days
Safety and tolerability of COVID-19 HIPRA vaccine in healthy adult volunteers	Change from baseline in safety laboratory parameters at 7 days following each vaccination.	7 days
Safety and tolerability of COVID-19 HIPRA vaccine in healthy adult volunteers	Number and percentage of serious adverse events throughout the study duration.	30 weeks
Safety and tolerability of COVID-19 HIPRA vaccine in healthy adult volunteers	Number and percentage of adverse events of special interest (AESI) throughout the study duration.	30 weeks
Safety and tolerability of COVID-19 HIPRA vaccine in healthy adult volunteers	Number and percentage of medically attended adverse events (MAAE) related to study vaccine throughout the study duration.	30 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Neutralization titer for each individual sample and GMT for group comparison at Day 21 and 35.	Day 21 and 35.
Immunogenicity	IC50 of beta and delta variants.	Day 21 and 35.
Immunogenicity	Geometric mean fold rise (GMFR) in neutralizing antibodies titers from baseline at Day 21 and 35.	Day 21 and 35.
Immunogenicity at long-term	Neutralization titer for each individual sample and GMT for group comparison at 24 and 48 weeks after the second dose.	24 and 48 weeks after the second dose
Immunogenicity at long-term	IC50 of beta and delta variants.	24 weeks after the second dose
Immunogenicity at long-term	GMFR in neutralizing antibodies titers from baseline at 24 weeks after the second dose.	24 weeks after the second dose
Immunogenicity to the SARS-CoV-2 spike glycoprotein	Total binding antibody titer and GMT for group comparison at Day 21 and 35.	Day 21 and 35
Immunogenicity to the SARS-CoV-2 spike glycoprotein	GMFR in total binding antibodies titer from baseline at Day 21 and 35.	Day 21 and 35
Immunogenicity to the SARS-CoV-2 spike glycoprotein at long-term	Total Binding antibody titer and GMT for group comparison at 24 weeks after the second dose.	24 weeks after the second dose
Immunogenicity to the SARS-CoV-2 spike glycoprotein at long-term	GMFR in total binding antibodies titer from baseline at 24 weeks after the second dose.	24 weeks after the second dose
Immunogenicity to the SARS-CoV-2 spike glycoprotein	Percentage of subjects who seroconverted defined as a ≥4-fold change in total binding antibody titer from baseline at Day 21 and 35.	Day 21 and 35.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with symptomatic SARS-CoV-2 infections in participants without evidence of infection before COVID-19 HIPRA vaccination.	Number and percentage of subjects with symptomatic SARS-CoV-2 infections according to COVID-19 infection criteria.	30 weeks
Number of COVID-19 severe infections after receiving COVID-19 HIPRA vaccine.	Number and percentage of COVID-19 severe infections throughout the study duration.	30 weeks
Number of COVID-19 severe infections after receiving COVID-19 HIPRA vaccine.	Number and percentage of hospital admissions associated with COVID-19 throughout the study duration.	30 weeks
Number of COVID-19 severe infections after receiving COVID-19 HIPRA vaccine.	Number and percentage of intensive care unit (ICU) admissions associated with COVID-19 throughout the study duration.	30 weeks
Number of COVID-19 severe infections after receiving COVID-19 HIPRA vaccine.	Number and percentage of deaths associated with COVID-19 throughout the study duration.	30 weeks

Collaborators and Investigators

• Sponsor: Hipra Scientific, S.L.U
• Collaborators: National Institute of Hygiene and Epidemiology, Vietnam; Laboratorios Hipra, S.A.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2021
• Primary Completion (Actual): December 27, 2021
• Study Completion (Actual): May 6, 2022

Study Registration Dates

• First Submitted: November 17, 2021
• First Submitted That Met QC Criteria: December 1, 2021
• First Posted (Actual): December 2, 2021

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Respiration Disorders; Respiratory Tract Diseases
• Other Study ID Numbers: HAN-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No