Efficacy and Safety of hzVSFv13 in Patients With COVID-19 Pneumonia

Study Overview
=================
Brief Summary
-----------------
To explore the efficacy and confirm the safety of the concomitant administration of the standard of care and hzVSF-v13 in patients with COVID-19 infection

Detailed Description
-----------------
A Multi center, Randomized, Double-blind, Parallel design

Official Title
-----------------
A Multi Center, Randomized, Double-blind, Parallel Design, Phase 2 Study to Evaluate the Efficacy and Safety of hzVSFv13 Compared to Standard of Care After Intravenous(IV) Administration With Add-on Standard of Care in COVID-19 Moderate to Severe Patients

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Drug: hzVSF-v13
* Drug: Placebo (Normal saline solution)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults aged at least 19 years at screening Those who have been admitted or scheduled to be admitted due to a diagnosis with COVID-19 by RT-PCR test within 4 days prior to screening Patients whose findings of COVID-19 pneumonia have been confirmed by radiographic tests (CT and X-ray) at screening (e.g., ground glass opacity (GGO), crazy-paving pattern, or consolidation) Those who fall under the following at screening: - Patients identified as moderate: Oxygen saturation in the atmosphere (SpO2) >93% (to be confirmed with respiratory rate ≥20/min or pulse rate ≥90 beats/min secondarily) Patients identified as severe: Oxygen saturation in the atmosphere (SpO2) ≤93% or PaO2/FiO2 <300 (respiratory rate ≥30/min or pulse rate ≥125 beats/min secondarily) Those who have voluntarily provided a written consent to participate in this clinical study Exclusion Criteria: Individuals with a clinically significant history of hypersensitivity reactions to the components of hzVSF-v13, drugs containing components of the same class, or other drugs (aspirin, non-steroidal anti-inflammatory drugs, antibiotics, etc.) Individuals with a severe at screening - Breathing disorder that requires treatment of one or more of the following: Oxygen therapy using high-flow nasal cannula (HFNC), Noninvasive positive pressure ventilation (NIV), invasive mechanical ventilation, ECMO, Clinical diagnosis of respiratory failure - Shock (Systolic <90mmHg or diastolic <60mmHg, or in case need a blood pressure booster) - Multiple organ failure Patients with pneumonia other than due to the novel coronavirus (SARS-CoV-2) infection (e.g., influenza virus pneumonia, bacterial pneumonia, and fungal pneumonia) Patients with severe heart failure (NYHA Class III or higher) Pregnant women Men or women of childbearing potential who are planning to become pregnant or do not agree to use one or more of the clinically appropriate methods of contraception below from the first day until 120 days after the last day of investigational product administration ① Surgical infertility (e.g., bilateral tubal ligation, vasectomy) ② Hormonal contraceptives (Hormone releasing IUD, implantable form, patch, oral hormone) ③ Double-barrier method (concomitant use of two of the following: IUD, male or female condom, contraceptive diaphragm, contraceptive sponge, cervical cap, spermicide) Periodic abstinence (e.g., calendar, ovulation date, basal body temperature, post-ovulation methods) and coitus interruptus are not permitted as appropriate contraceptive methods, and effective contraceptive methods must be kept being used during the course of the clinical study. Those who are scheduled to have organ transplantation Those who have laboratory test results that fall under the following values at screening ① ALT or AST ≥5 times the upper limit of normal (ULN) ② eGFR < 30 mL/min/1.73m2 ③ platelets < 50,000/mm3 Those who have a positive result for serology (hepatitis B, human immunodeficiency virus [HIV], and hepatitis C tests) at screening Those who administered other investigational products within 30 days prior to the screening visit Others who have been determined to be ineligible to participate in the clinical study according to the investigator's medical opinion

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard of care + 3 doses of hzVSF-v13 50 mg/dose IV<br>Standard of care + 3 doses of hzVSF-v13 50 mg/dose IV | Drug: hzVSF-v13<br>* Drug: hzVSF-v13 Dosage form: hzVSF-v13 40mg/mL in a 5mL vial Frequency: Dose at Day 1, 3, 7 Other names: a humanized monoclonal antibody (mAb)<br>* Other names: a humanized monoclonal antibody (mAb);|
| Experimental: Standard of care + 3 doses of hzVSF-v13 200 mg/dose IV<br>Standard of care + 3 doses of hzVSF-v13 200 mg/dose IV | Drug: hzVSF-v13<br>* Drug: hzVSF-v13 Dosage form: hzVSF-v13 40mg/mL in a 5mL vial Frequency: Dose at Day 1, 3, 7 Other names: a humanized monoclonal antibody (mAb)<br>* Other names: a humanized monoclonal antibody (mAb);|
| Experimental: Standard of care + 1 dose of hzVSF-v13 200 mg/dose IV + 2 doses of the placebo<br>Standard of care + 1 dose of hzVSF-v13 200 mg/dose IV + 2 doses of the placebo | Drug: hzVSF-v13<br>* Drug: hzVSF-v13 Dosage form: hzVSF-v13 40mg/mL in a 5mL vial Frequency: Dose at Day 1, 3, 7 Other names: a humanized monoclonal antibody (mAb)<br>* Other names: a humanized monoclonal antibody (mAb);|
| Placebo Comparator: Standard of care + 3 doses of the placebo to match hzVSF-v13 (normal saline)<br>Standard of care + 3 doses of the placebo to match hzVSF-v13 (normal saline) | Drug: Placebo (Normal saline solution)<br>* Dosage form: 0.9% NaCl solution Frequency: Dose at Day 1, 3, 7<br>* Other names: 0.9% Normal saline;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in the clinical improvement score on an 8-point scale at Day 21 | Descriptive statistics for the changes from baseline in the clinical improvement score on an 8-point scale at Day 21 shall be presented for each treatment group, and a two-sample t-test or the Wilcoxon rank-sum test shall be performed depending on whether the normality assumption is satisfied in order to test differences of each study group compared to the control group. | Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in the clinical improvement score on an 8-point scale at Day 7, Day 14, and Day 28 | Descriptive statistics for the changes from baseline in the clinical improvement score on an 8-point scale at Day 7, Day 14, and Day 28 shall be presented for each treatment group, and a two-sample t-test or the Wilcoxon ranksum test shall be performed depending on whether the normality assumption is satisfied in order to test differences of each study group compared to the control group. | Day 7, Day 14, Day 28 | 
| Time to discontinuation of oxygen therapy after investigational product administration | The Kaplan-Meier curves for the time to discontinuation of oxygen therapy after investigational product administration shall be presented, and the median time and 95% confidence interval will be presented by treatment group. In addition, a log-rank test shall be performed, if necessary, to test differences of each study group compared to the control group. | Day 28 | 
| Time to recovery* after investigational product administration (days) | *0 to 3 points in the clinical improvement score on an 8-point scale The Kaplan-Meier curves for the time to recovery after investigational product administration shall be presented, and the median time and 95% confidence interval will be presented by treatment group. In addition, a log-rank test shall be performed, if necessary, to test differences of each study group compared to the control group. | Day 28 | 
| Changes from baseline in PaO2/FiO2 at Day 7, Day 14, Day 21, and Day 28 | Descriptive statistics for the changes from baseline in PaO2/FiO2 at Day 7, Day 14, Day 21, and Day 28 shall be presented for each treatment group, and a two-sample t-test or the Wilcoxon rank-sum test shall be performed depending on whether the normality assumption is satisfied in order to test differences of each study group compared to the control group. | Day 7, Day 14, Day 21, Day 28 | 
| Changes from baseline in the NEWS 2 score at Day 7, Day 14, Day 21, and Day 28 | Descriptive statistics for the changes from baseline in the NEWS 2 score at Day 7, Day 14, Day 21, and Day 28 shall be presented for each treatment group, and a two-sample t-test or the Wilcoxon rank-sum test shall be performed depending on whether the normality assumption is satisfied in order to test differences of each study group compared to the control group. | Day 7, Day 14, Day 21, Day 28 | 
| Mortality at Day 28 and Day 60 after investigational product administration | The frequency and percentage for the proportion of subjects who died at Day 28 and Day 60 after investigational product administration shall be presented for each treatment group, and the Pearson's chi-squared test or the Fisher's exact test shall be performed to test differences of each study group compared to the control group. | Day 28, Day 60 |