Clinical trial NCT05696067: Evaluation of Corfluvec Vaccine for the Prevention of COVID-19 in Healthy Volunteers
Official title: Randomized, Double-blind, Placebo-controlled Phase 1/2 Trial of Corfluvec Intranasal Vector Vaccine for the Prevention of COVID-19 in Healthy Volunteers Aged 18 to 60 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: COVID-19
Keywords: COVID-19
vaccine
influenza vector
Lead sponsor: Research Institute of Influenza, Russia
Sponsor class: OTHER
Collaborators: name: MDP-CRO, LLC
name: St. Petersburg State Pavlov Medical University
First posted: 2023-01-25
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of the study is to investigate the safety and immunogenicity of a two-component intranasal vaccine for the prevention of COVID-19 in healthy volunteers 18-60 years old

Detailed description: Study include three parts. During the first part the two vaccine components will be administered separately to a small number of seronegative participants in low dose and then high dose to evaluate each component's safety. During the second part vaccine components would be administered one after another with 21 days interval to evaluate safety of the complete vaccine regimen (low dose and high dose). During the third part of the study the high dose vaccine will be administered to participants to evaluate vaccine immunogenicity. The whole study will include 200 participants. Duration of the study for each participant is about 6.5 months (no more than 194 days).

Eligibility criteria: Inclusion Criteria:

1. Availability of signed informed consent
2. Adult men and women aged 18-60
3. Diagnosed "healthy" according to the data of standard clinical, laboratory and instrumental examination methods, with the absence of clinically significant changes
4. Body Mass Index (BMI): 18.5≤ BMI ≤30 kg/m2
5. HI antibody titers ≤1:20 to influenza A/H1N1pdm09 and A/H3N2 (only for phase 1)
6. Serum antibodies to the SARS-CoV-2 N-protein not higher than 100 BAU/ml
7. The ability and willingness to make entries in the diary of self-observation, as well as to carry out all the visits foreseen in the study for control medical observation
8. Negative test for alcohol in exhaled air
9. Consent to use effective contraceptive methods throughout their participation in the study
10. Values of the complete blood count and biochemical blood analysis (during the screening) within 0.9\*reference range lower limit and 1,1 \* reference range upper limit
11. Negative tests for HIV, hepatitis B, hepatitis C, and syphilis

Exclusion Criteria:

1. Contact with COVID-19 patients within 14 days prior to the start of the clinical study
2. Positive rapid test result for SARS-CoV-2 antigen
3. Participation in another clinical study within three months prior to the start of the current study; planning to participate in another study during the current study period.
4. Immunization with any other non-study vaccine product, including COVID-19 vaccination within four weeks prior to enrollment in the current study, or refusal to postpone such until the end of the four-week period after completion of the current study
5. Regular use of nasal irrigation therapy during the last six months prior to enrollment in the current study or episodic use of the above method of treatment in the two weeks prior to the screening
6. History of frequent nosebleeds (\>5) during the year prior to the current study
7. Clinically significant anatomic pathology or the presence of surgical intervention in the sinus area, paranasal sinuses, or traumatic injuries of the nose within a month before screening
8. Symptoms of acute respiratory disease, including fever, or other acute illness at the time of screening or within two weeks prior to screening
9. Treatment with immunoglobulins or other blood derived medications in the three months prior to screening or planning such treatment during the period of participation in the current study; donation of blood/plasma (450 ml or more) less than 2 months prior to screening
10. The presence or suspicion of the presence of various immunosuppressive or immunodeficiency conditions or continuous use (the drug was prescribed for more than 14 days without a break) of immunosuppressive drugs, immunomodulators for 6 months before the screening
11. History of bronchial asthma
12. Hypersensitivity and the presence of severe allergic reactions, including Quincke's edema, anaphylactic shock after the previous administration of any vaccine
13. History of wheezing after previous immunization with live influenza vaccine
14. Other adverse events after immunization (fever above 40°C, syncope, non-febrile convulsions, anaphylaxis) when there is a minimal likelihood that they are associated with a previous administration of any vaccine
15. Suspicion of hypersensitivity to any component of the study vaccine, including egg protein
16. Seasonal (in spring or autumn) increased sensitivity to the effects of natural factors
17. Acute or chronic clinically significant lung, cardiovascular, hepatic, endocrine, neurological, or psychiatric disorders, or impaired renal function identified by history, physical examination, or clinical laboratory findings that, in the opinion of the investigator, may influence the outcome of the study
18. History of leukemia or any other malignant diseases of the blood or solid malignant neoplasms of other organs
19. History of thrombocytopenic purpura or bleeding disorders
20. History of convulsions
21. The presence or suspicion of the presence of various immunosuppressive or immunodeficiency conditions, including HIV infection
22. Tuberculosis or residual changes after tuberculosis according to the anamnesis and / or available medical documentation
23. Chronic alcohol dependence or chronic use of illicit drugs, drug abuse
24. Claustrophobia and social phobia according to history and / or available medical records
25. For women of reproductive age - lactation, pregnancy or suspected pregnancy, early postpartum period
26. Premenopausal women (last menstrual period \<1 year prior to signing informed consent) who are not surgically sterile and women who are of reproductive potential but do not use or plan to use valid birth control throughout the study and do not agree to perform a urine pregnancy test while participating in the study
27. Military personnel undergoing military service on conscription
28. Persons in custody in pre-trial detention centers and serving sentences in places of deprivation of liberty
29. Special diet (eg, vegetarian, vegan, salt-restricted) or lifestyle (night work, extreme physical activity)
30. Any condition that, in the opinion of the investigator, may increase the risk to the health of a volunteer participating in the study or affect the results of the study

Primary outcomes:
measure: Number of participants with local and systemic adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Throughout the study, average of 6.5 months
measure: Level of SARS-CoV-2 antigen specific cytokine producing T-cells
timeFrame: Throughout the 42±2 study days
measure: Level of SARS-CoV-2 antigen specific cytokine release in whole blood assay
timeFrame: Throughout the 42±2 study days
measure: Level of SARS-CoV-2 antigen specific mucosal and systemic IgA and IgG antibody
timeFrame: Throughout the 42±2 study days
Secondary outcomes:
measure: Number of responders to vaccination according to the fold increase in the level of specific T-cell response
timeFrame: Days 7, 21, 27, 42±2
measure: Seroconversion rate of SARS-CoV-2 antigen specific antibody
timeFrame: Days 21, 42±2
Other outcomes:
measure: Concentration of cytokines in nasal secrets after vaccination
timeFrame: Throughout the first 48h of the study
measure: Influenza specific local and systemic antibody immune response
timeFrame: Throughout the 42±2 study days
measure: SARS-CoV-2 and influenza specific antibody and T-cell immune response (follow-up)
timeFrame: Days 90±3, 180±5
measure: Efficacy against symptomatic COVID-19 and influenza
timeFrame: Throughout the study, average of 6.5 months
Locations:
city: Saint Petersburg
country: Russian Federation
facility: Pavlov First State Medical University of St. Petersburg
city: Saint Petersburg
country: Russian Federation
facility: Smorodintsev Research Institute of Influenza
Study officials:
References: