Safety and Immunogenicity of COVI-VAC, a Live Attenuated Vaccine Against COVID-19

Study Overview
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Brief Summary
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This is the first study of COVI-VAC in humans. The purpose of the study is to evaluate the safety and immune response of COVI-VAC (a live attenuated vaccine to prevent COVID-19) in healthy adults aged 18 to 30 years. Approximately 48 participants will be enrolled into 1 of 3 dose groups (low, medium, high). Within each of these dose groups, participants will be assigned randomly to receive either 2 doses of COVI-VAC 28 days apart, 2 doses of placebo (saline), or 1 dose of COVI-VAC and 1 dose of placebo. COVI-VAC or placebo is administered by drops into each nostril. Neither the participants nor the researchers will know whether COVI-VAC or placebo has been received. To assess the safety of the vaccine, each participant will record symptoms and oral temperature in a diary daily for 14 days after each dose. Safety laboratory tests, physical exams, ECGs, and a chest X-ray will also be performed, and peak expiratory flow and vital signs will be measured. Adverse events and medication use will be recorded. Blood samples and intranasal samples will be collected to assess the immune response from the vaccine.

Official Title
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First-in-human, Randomised, Double-blind, Placebo-controlled, Dose-escalation Study in Healthy Young Adults Evaluating the Safety and Immunogenicity of COVI-VAC, a Live Attenuated Vaccine Candidate for Prevention of COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Biological: COVI-VAC
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who meet all of the following criteria may be included in the study: Men and women aged between 18 to 30 years of age, inclusive, on the day of signing the informed consent form (ICF) In good health with no history, or current evidence, of clinically significant medical conditions with particular reference to, but not restricted to, hypertension, diabetes, thromboembolic disorders, coronary heart disease, chronic obstructive lung disease, and no clinically significant test abnormalities that will interfere with subject safety, as defined by medical history, physical examination, vital signs (including oxygen saturation), ECG, spirometry, and safety laboratory tests as determined by the Investigator Total body weight of greater or equal to 50 kg and body mass index (BMI) greater or equal to 18.0 kg/m2 and less than or equal to 28.0 kg/m2 (the upper limit of the BMI may be increased to less than or equal to 30 kg/m2 at the Investigator's discretion in case of a muscular healthy subject for whom BMI may be biased upwards) Negative drugs of abuse, cotinine, and alcohol screen (unless explained by prescribed medication) Negative pregnancy test for women who have not been surgically sterilised Negative COVID Clear test Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from the study: Haemoglobin A1c ≥6.0% or 42 mmol/mol Forced expiratory volume in 1 second (FEV1) less than 80% predicted value Signs or symptoms suggestive of upper or lower respiratory tract infection (including fever or persistent cough) within 28 days of Day 1 Pregnant, possibly pregnant, or lactating women Women who have been pregnant through the third trimester or given birth within the past 6 months Planning a pregnancy (subject or partner) within 90 days after the last IMP dose Inadequate venous access for repeated phlebotomy History of confirmed or suspected SARS-CoV-2 infection Contact with any individual subsequently confirmed to have SARS-CoV-2 within 14 days after contact History of wheeze treated with inhaler(s) Respiratory symptoms, including wheeze, that have ever resulted in hospitalisation Known bronchial hyperreactivity to viruses Any significant abnormality altering the anatomy of the nose in a substantial way or nasopharynx that may interfere with the aims of the study and in particular any of the nasal assessments or viral challenge (historical nasal polyps can be included, but large nasal polyps causing current and significant symptoms and/or requiring regular treatments in the last month are excluded)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Saline<br>Normal saline | Other: Placebo<br>* normal saline<br>|
| Experimental: Low dose cohort 1<br>COVI-VAC, single dose | Biological: COVI-VAC<br>* intranasal, live attenuated vaccine against SARS-CoV-2<br>|
| Experimental: Medium dose cohort 1<br>COVI-VAC, single dose | Biological: COVI-VAC<br>* intranasal, live attenuated vaccine against SARS-CoV-2<br>|
| Experimental: High dose cohort 1<br>COVI-VAC, single dose | Biological: COVI-VAC<br>* intranasal, live attenuated vaccine against SARS-CoV-2<br>|
| Experimental: Low dose cohort 2<br>COVI-VAC, two doses 28 days apart | Biological: COVI-VAC<br>* intranasal, live attenuated vaccine against SARS-CoV-2<br>|
| Experimental: Medium dose cohort 2<br>COVI-VAC, two doses 28 days apart | Biological: COVI-VAC<br>* intranasal, live attenuated vaccine against SARS-CoV-2<br>|
| Experimental: High dose cohort 2<br>COVI-VAC, two doses 28 days apart | Biological: COVI-VAC<br>* intranasal, live attenuated vaccine against SARS-CoV-2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reactogenicity | Percentage of subjects with reactogenicity events | 14 days after each dose | 
| Adverse events | Percentage of subjects with adverse events | Days 1 through 57 | 
| Serious adverse events | Percentage of subjects with serious adverse events | Days 1-400 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IgG titre | IgG titre measured by ELISA in serum collected on Days 1, 15, 29, 43, 57, 120, 210, and 400 | Days 1, 15, 29, 43, 57, 120, 210, and 400 | 
| Neutralizing antibody titre | Neutralising antibody level measured by microneutralisation assay in serum | Days 1, 15, 29, 43, 57, 120, 210, and 400 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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live attenuated, live attenuated vaccine, SARS-CoV-2, COVID-19