Covid19, SARS CoV 2 Infection
Conditions
Brief summary
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
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
Interventions
BIOLOGICALCOVID-19 vaccine HIPRA 10
One sentinel subject and 4 additional subjects will be assigned to COVID-19 vaccine HIPRA 10 µg
BIOLOGICALCOVID-19 vaccine HIPRA 20
One sentinel subject and 9 additional subjects will be assigned to COVID-19 vaccine HIPRA 20 µg
BIOLOGICALCOVID-19 vaccine HIPRA 40
One sentinel subject and 9 additional subjects will be assigned to COVID-19 vaccine HIPRA 40 µg
BIOLOGICALCommercial COVID-19 vaccine
One subject in cohort 1 and 2 subjects in Cohort 2 and 3 will be assigned to Commercial COVID-19 vaccine
Sponsors
Laboratorios Hipra, S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 |
| Change from baseline in hematology and biochemistry laboratory values at 7 days following each vaccination | 7 days |
| 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 |
| Binding antibody IgG titer measured for each individual sample and GMT for group comparison at Day 21 and 35 | Day 21 and 35 |
| Number and percentage of serious adverse events throughout the study duration. | 357 days |
Countries
Spain
Outcome results
None listed