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)

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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COVID-19, SARS-CoV-2 Acute Respiratory Disease

Intervention / Treatment
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* Biological: COVID-19 Vaccine HIPRA
* Biological: Cominarty (Pfizer-BioNtech)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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. |