Evaluation of Inactivated Vaccine in Healthy Adults Against Coronavirus Disease of 2019 (COVID-19)

Study Overview
=================
Brief Summary
-----------------
In this phase 1 study, the inactivated virus vaccine National Research Centre (NRC) Vaccine-101 (VACC-101) will be investigated for its safety and immunogenicity in healthy volunteers with the aim of providing effective and safe protection against COVID-19.

Detailed Description
-----------------
This is a Phase I, Randomized, Open-Labeled Clinical trial. Eligible volunteers will be randomized in a 1:1:1 allocation ratio, into one of the three study arms using the Interactive Web Response Technology (IWRS). Unscheduled visits can occur at any time during the study period outside the initially planned study visits, all the extra visits will be documented in the subjects' files. Volunteers will be randomized into one of the following arms to receive different doses of the Inactivated SARS-COV-2 Vaccine NRC-VACC-101 as an intramuscular (IM) Injection or Placebo: Arm One: Volunteers will receive two IM doses of the vaccine, concentrations of 3 mcg, 28 days apart. Arm Two: Volunteers will receive two IM doses of the vaccine, concentrations of 6 mcg, 28 days apart. Arm Three (Control arm): Volunteers will receive two IM doses of the placebo, 28 days apart. The first 9 subjects will be initially vaccinated with their first dose, as per their assigned study arm determined by the randomization procedures and will be followed up until day 14 (visit 03). At this point in the study, the Data Safety and Monitoring Board (DSMB) will review safety data before proceeding with vaccinating the rest of the recruited subjects

Official Title
-----------------
A Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of Inactivated Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Vaccine Against COVID-19 in Healthy Adults

Conditions
-----------------
COVID-19, Vaccine Reaction, Vaccine Adverse Reaction

Intervention / Treatment
-----------------
* Biological: Covi Vax


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults with age 18 to 50 years. Willingness. For married females of childbearing age: Willingness to practice continuous effective contraception for one year from the start of the study. Agreement to refrain from blood donation during the study. Body temperature is within the normal range (36.5 - 37.5°C). General good health as established by medical history, physical and laboratory examinations. Exclusion Criteria: Pregnancy or lactation. Inability to provide informed consent. Recent receipt of any vaccination within 30 days prior to baseline. Planning to receive any vaccination during the course of the study. Prior receipt of Adenovirus vaccine, or any other Coronavirus vaccine. Recent receipt of any immunoglobulin within 90 days prior to baseline. Recent receipt of any blood product within 90 days prior to baseline. Volunteers who are immunosuppressed or receiving immunosuppressive medications, including: HIV infection, asplenia, recurrent severe infections, and the use of immunosuppressive medications within the past 6 months, except for topical steroids or short-term oral steroids (course lasting < 14 days). Currently taking any product (investigational or off-label) for prevention of COVID-19 disease. Having any autoimmune disease. History of allergic reactions for any of the vaccine components. History of angioedema. History of anaphylaxis. History of cancer. History of serious psychiatric conditions that are likely to affect participation in the study. Having bleeding disorders. Having chronic respiratory diseases. Having chronic cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorders, and neurological illness. Volunteers with BMI ≥ 40 Kg/m2 or ≤ 18 Kg/m2. Current alcohol abuse. Drug abuse within 5 years prior to baseline. History of laboratory-confirmed COVID-19 or seropositivity for SARS-CoV-2 or positive serum immunoglobulin M (IgM) and immunoglobulin G (IgG) to the SARS CoV-2 or abnormal chest CT-Scan (COVID-19 image) or positive pharyngeal/sputum swabs for SARS-CoV-2. Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation. High-risk population (volunteers who work in front-line health facilities or were in close contact with confirmed COVID-19 cases). Living in the same household as anyone at high risk of severe COVID-19. Any condition, according to the judgment of the investigator, that would interfere with the subject's ability to comply with all study requirements or that would place the subject at unacceptable risk by his/her participation in the study or impair the interpretation of the study data.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Randomized, Open-label, Phase 1 Clinical trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NRC-VACC-101 vaccine 3 microgram<br>Volunteers will receive two IM doses of the vaccine, concentrations of 3 mcg, 28 days apart. | Biological: Covi Vax<br>* Inactivated SARS-COV-2 Vaccine/alum adjuvant preparation in addition to excipients (NRC-VACC- 101) administered as an IM Injection. NRC-VACC-101 is provided as a single dose of inactivated vaccine of opaque white liquid free from visible particles filled in injection vial (2R) glass vials. Each Dose of Covi Vax Vaccine contains 6 mcg antigen of A human coronavirus (hCoV)-19/Egypt/NRC-03/2020 SARS-CoV-2 strain.<br>* Other names: NRC Inactivated SARS-CoV-2 Vaccine;|
| Active Comparator: NRC-VACC-101 vaccine 6 microgram<br>Volunteers will receive two IM doses of the vaccine, concentrations of 6 mcg, 28 days apart. | Biological: Covi Vax<br>* Inactivated SARS-COV-2 Vaccine/alum adjuvant preparation in addition to excipients (NRC-VACC- 101) administered as an IM Injection. NRC-VACC-101 is provided as a single dose of inactivated vaccine of opaque white liquid free from visible particles filled in injection vial (2R) glass vials. Each Dose of Covi Vax Vaccine contains 6 mcg antigen of A human coronavirus (hCoV)-19/Egypt/NRC-03/2020 SARS-CoV-2 strain.<br>* Other names: NRC Inactivated SARS-CoV-2 Vaccine;|
| Placebo Comparator: Control arm<br>Volunteers will receive two IM doses of the placebo (excipients only), 28 days apart. | Biological: Covi Vax<br>* Inactivated SARS-COV-2 Vaccine/alum adjuvant preparation in addition to excipients (NRC-VACC- 101) administered as an IM Injection. NRC-VACC-101 is provided as a single dose of inactivated vaccine of opaque white liquid free from visible particles filled in injection vial (2R) glass vials. Each Dose of Covi Vax Vaccine contains 6 mcg antigen of A human coronavirus (hCoV)-19/Egypt/NRC-03/2020 SARS-CoV-2 strain.<br>* Other names: NRC Inactivated SARS-CoV-2 Vaccine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety of NRC-VACC-101 Vaccine | To evaluate the safety of the proposed regimens of NRC-VACC-101 | Follow up for any solicited adverse event(AE) reported within 7 days | 
| The tolerability of NRC-VACC-101 Vaccine | To evaluate the tolerability of the proposed regimens of NRC-VACC-101 Vaccine in the healthy population | Follow up for any AE within 28 days of each dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The seroconversion rate of neutralizing antibodies | To evaluate the seroconversion rate of neutralizing antibodies resulting from the NRC-VACC-101 Vaccine | The evaluation of the antibody will be measured up to one month of each dose | 
| To recommend the dose level of NRC-VACC-101 Vaccine for the phase II trial. | The evaluation of the Microneutralization Assay curve will give an overview of the dose possible suggested dose of NRC-VACC-101 Vaccine for the phase II trial | The evaluation of the Microneutralization Assay will be assessed up to one month of each dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19, Inactivated SARS-CoV-2 Vaccine, NRC-VACC-101, Vaccine Safety, Vaccine Tolerability, Vaccine Immunogenicity, Covi Vax, Egyptian Inactivated SARS-CoV-2 Vaccine