Safety and Immunogenicity Study of Recombinant Protein RBD Candidate Vaccine Against SARS-CoV-2 in Adult Healthy Volunteers (COVID-19)

Study Overview
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Brief Summary
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This is a first-in-human, phase I/IIa, randomized, controlled, observer-blinded, dose-escalation, multicentre clinical trial to evaluate safety and immunogenicity of COVID-19 HIPRA vaccine in adult healthy volunteers.

Detailed Description
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The study population includes 30 healthy adults aged 18-39 which will be distributed in 3 cohorts, receiving three different doses of antigen, 10 µg, 20 µg and 40 µg. In each cohort, patients will be randomized in ratio of 10:2 test:commercial vaccine, following an staggered enrolment with a sentinel subject in each cohort. Each participant will receive 2 immunisations separated by 21 days, and will be followed for 48 weeks after the second dose

Official Title
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A Phase I/IIa Study to Evaluate Safety and Immunogenicity of Recombinant Protein RBD Candidate Vaccine Against SARS-CoV-2 in Adult Healthy Volunteers

Conditions
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Covid19, SARS CoV 2 Infection

Intervention / Treatment
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* Biological: COVID-19 vaccine HIPRA 10
* Biological: COVID-19 vaccine HIPRA 20
* Biological: COVID-19 vaccine HIPRA 40
* Biological: Commercial COVID-19 vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults males or females between 18-39 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 PCR test and negative serum IgG binding antibody response to the SARS-CoV-2 S glycoprotein at screening or prior the first vaccination. 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 18 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 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 (e-g- ongoing severe depression, history of admission to an in-patient psychiatric facility, recent suicidal ideation, history of suicide attempt, 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) 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

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: Parallel 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 10<br>* One sentinel subject and 4 additional subjects will be assigned to COVID-19 vaccine HIPRA 10 µg<br>* Other names: COHORT 1;Biological: COVID-19 vaccine HIPRA 20<br>* One sentinel subject and 9 additional subjects will be assigned to COVID-19 vaccine HIPRA 20 µg<br>* Other names: COHORT 2;Biological: COVID-19 vaccine HIPRA 40<br>* One sentinel subject and 9 additional subjects will be assigned to COVID-19 vaccine HIPRA 40 µg<br>* Other names: COHORT 3;|
| Active Comparator: Commercial COVID-19 vaccine<br>Subjects will receive 2 injections of commercial COVID-19 vaccine administered 21 days apart. | Biological: Commercial COVID-19 vaccine<br>* One subject in cohort 1 and 2 subjects in Cohort 2 and 3 will be assigned to Commercial COVID-19 vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of solicited local and systemic reactogenicity adverse events for 7 days following each vaccination. |  | 7 days | 
| Number and percentage of unsolicited local and systemic reactogenicity adverse events for 28 days following each vaccination. |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in hematology and biochemistry laboratory values at 7 days following each vaccination |  | 7 days | 
| Number and percentage of serious adverse events throughout the study duration. |  | 357 days | 
| Number and percentage of adverse events of special interest (AESI) throughout the study |  | 357 days | 
| Number and percentage of medically attended adverse events (MAAE) related to study vaccine throughout the study duration |  | 357 days | 
| Neutralization titer measured as Inhibitory concentration 50 (IC50) for each individual sample and geometric mean titer (GMT) for group comparison at Day 21 and 35 |  | Day 21 and 35 | 
| Geometric mean fold rise (GMFR) in neutralizing antibodies titers from baseline at Day 21 and 35. |  | Day 21 and 35 | 
| Neutralization titer measured as IC50 for each individual sample and GMT for group comparison at 24 and 48 weeks after the second dose |  | week 27 and week 51 | 
| GMFR in neutralizing antibodies titers from baseline at 24 and 48 weeks after the second dose. |  | week 27 and week 51 | 
| Binding antibody IgG titer measured for each individual sample and GMT for group comparison at Day 21 and 35 |  | Day 21 and 35 | 
| GMFR in IgG titer from baseline at Day 21 and 35 |  | Day 21 and 35 | 
| Binding antibody IgG titer measured for each individual sample and GMT for group comparison at 24 and 48 weeks after the second dose. |  | week 27 and week 51 | 
| GMFR in IgG titer from baseline at 24 and 48 weeks after the second dose |  | week 27 and week 51 | 
| T-cell-mediated response to the SARS-CoV-2 S protein as measured by whole PBMC stimulation by ELISpot at baseline and at Day 35. |  | Day 35 | 
| CD4+/CD8+ T-cell response to the SARS-CoV-2 S protein as measured by in vitro PBMC stimulation by cytokine staining assays at baseline and at Day 35 |  | Day 35 |