Clinical trial NCT05007509: Safety and Immunogenicity Study of Recombinant Protein RBD Candidate Vaccine Against SARS-CoV-2 in Adult Healthy Volunteers (COVID-19)
Official title: A Phase I/IIa Study to Evaluate Safety and Immunogenicity of Recombinant Protein RBD Candidate Vaccine Against SARS-CoV-2 in Adult Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Covid19
SARS CoV 2 Infection
Lead sponsor: Laboratorios Hipra, S.A.
Sponsor class: INDUSTRY
First posted: 2021-08-16
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Eligibility criteria: 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.

Primary outcomes:
measure: Number and percentage of solicited local and systemic reactogenicity adverse events for 7 days following each vaccination.
timeFrame: 7 days
measure: Number and percentage of unsolicited local and systemic reactogenicity adverse events for 28 days following each vaccination.
timeFrame: 28 days
Secondary outcomes:
measure: Change from baseline in hematology and biochemistry laboratory values at 7 days following each vaccination
timeFrame: 7 days
measure: Number and percentage of serious adverse events throughout the study duration.
timeFrame: 357 days
measure: Number and percentage of adverse events of special interest (AESI) throughout the study
timeFrame: 357 days
measure: Number and percentage of medically attended adverse events (MAAE) related to study vaccine throughout the study duration
timeFrame: 357 days
measure: 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
timeFrame: Day 21 and 35
measure: Geometric mean fold rise (GMFR) in neutralizing antibodies titers from baseline at Day 21 and 35.
timeFrame: Day 21 and 35
measure: Neutralization titer measured as IC50 for each individual sample and GMT for group comparison at 24 and 48 weeks after the second dose
timeFrame: week 27 and week 51
measure: GMFR in neutralizing antibodies titers from baseline at 24 and 48 weeks after the second dose.
timeFrame: week 27 and week 51
measure: Binding antibody IgG titer measured for each individual sample and GMT for group comparison at Day 21 and 35
timeFrame: Day 21 and 35
measure: GMFR in IgG titer from baseline at Day 21 and 35
timeFrame: Day 21 and 35
measure: Binding antibody IgG titer measured for each individual sample and GMT for group comparison at 24 and 48 weeks after the second dose.
timeFrame: week 27 and week 51
measure: GMFR in IgG titer from baseline at 24 and 48 weeks after the second dose
timeFrame: week 27 and week 51
measure: 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.
timeFrame: Day 35
measure: 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
timeFrame: Day 35
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Girona
country: Spain
facility: Hospital Universitari Dr. Josep Trueta
Study officials:
affiliation: Laboratorios Hipra, S.A.
name: Elia Torroella
role: STUDY_CHAIR
References: