JS016 (Anti-SARS-CoV-2 Monoclonal Antibody)With Mild and Moderate COVID-19 or SARS-CoV-2 Asymptomatic Infection Subects

Study Overview
=================
Brief Summary
-----------------
JS016-002-Ib/II is a randomized, double-blinded, placebo-controlled study, to investigate the safety, PK profiles, preliminary efficacy and immunogenicity of intravenous Recombinant Human Anti-SARS-CoV-2 Monoclonal Antibody (JS016) in participants with mild and moderate COVID-19 or of SARS-CoV-2 Asymptomatic Infection. Three doses of JS016 are to be investigated, including 25mg/kg, 50mg/kg and 100mg/kg, given as single dose of intravenous infusion. In total, 90 participants will be enrolled with 30 participants each for 25, 50 and 100mg/kg dose cohort at a ratio of 2:1 to receive investigational product or placebo treatment, respectively.

Detailed Description
-----------------
Each participant will receive JS016 or matched placebo intravenous infusion on D1 (randomizing day). Non-pharmaceutical supportive background therapy (e.g. oxygen inhalation) for COVID-19 is allowed per clinical needs. Investigators will be kept blinded to review the preliminary efficacy and safety data on a regular basis. Meanwhile, a study evaluation team (SET) composed of medical monitors, safety assessors and statisticians will be set up to review the study status, safety and preliminary efficacy of the participants at the pre-specified time points or as necessary.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled, Phase Ib/II Clinical Study to Evaluate the Preliminary Efficacy, Safety, Pharmacokinetic Profiles and Immunogenicity of JS016 in Participants With Mild and Moderate COVID-19 or of SARS-CoV-2 Asymptomatic Infection

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

Intervention / Treatment
-----------------
* Biological: Recombinant Human Anti-SARS-CoV-2 Monoclonal Antibody(25mg/kg;50mg/kg;100mg/kg)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age of 18-65 years (inclusive) ,women or man SARS-CoV-2 detected in the diagnostic specimen (nasopharyngeal swab) High homology of viral gene sequencing with the known SARS-CoV-2. Mild/moderateillness COVID-19 or SARS-CoV-2 asymptomatic infection Within 7 days from the onset time of symptoms to randomization or within 5 days from the first time of SARS-CoV-2 positive test to randomization with required viral load No plan of pregnancy and being willing to use effective contraceptive measures Signed the informed consent form, sufficiently understanding of the content Exclusion Criteria: positive IgM/IgG against SARS-CoV-2 prior to randomization. Severeor critical illness Uncontrolled hypertension, cardiovascular/cerebrovascular diseases,lung diseases Type 1 diabetes, or newly diagnosed or poorly controlled type 2 diabetes Liver and kidney dysfunction, immune or inflammatory diseases, infections, surgery, tumors, and other major diseases History of SARS-CoV-2 vaccination or participation in clinical trial with neutralizing antibody against SARS-CoV-2. Use of therapeutic biologics within 3 months prior to screening, or within the elimination period (5 half-lives) of such drugs as the day of dosing Has participated in any other interventional clinical study involving anstudy drug within 3 months prior to screening, or within the elimination period (5 half-lives) of the study drug as the day of dosing Platelets and hemoglobin test results during screening period are abnormal and have clinical significanc. Anaphylaxis, urine drug screening, alcohol dependence, lactation during pregnancy, blood loss, and others

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Anti-SARS-CoV-2 Monoclonal Antibody dose 1/2/3<br>use Anti-SARS-CoV-2 Monoclonal Antibody,dose 1/2/3 to treat COVID-19 | Biological: Recombinant Human Anti-SARS-CoV-2 Monoclonal Antibody(25mg/kg;50mg/kg;100mg/kg)<br>* use dose 1/2/3 60 patients receipt JS016 intravenous infusion on day 1<br>|
| Placebo Comparator: Placebo<br>use placebo to treat COVID-19 | Drug: Placebo<br>* 30 patients receipt placebo intravenous infusion on day 1<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Measurs(Time to negative conversion in viral nucleic acid test(by RT-PCR) for diagnostic samples) | Time to negative conversion in viral nucleic acid test (by RT-PCR) for diagnostic samples, negative conversion is defined as two consecutive negative nucleic acid test for diagnostic samples after randomization | 0-85days | 
| Safety Measurements : 90 of participants with treatment-related adverse events as assessed byCTCAE v5.0 | Any adverse event, serious adverse events (SAEs) occurring during the clinical study, including clinical symptoms and abnormal vital signs, abnormal laboratory tests (complete blood cell count, serum chemistry, routine urinalysis, coagulation function, myocardial enzymogram, etc.) and abnormality of 12-lead ECGs will be observed for all the participants | 0-85days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK Measures:AUC0-tau | Area under the plasma drug concentration-time curve from time 0 to one dosing interval (AUC0-tau) | Day 0 to Day 85 | 
| PK Measures：Cmax | Maximum plasma drug concentration after administration (Cmax) | Day 0 to Day 85 | 
| PK Measures：Tmax | Time to the maximum plasma drug concentrations after administration (Tmax) | Day 0 to Day 85 | 
| PK Measures：t1/2 | Terminal half life (t1/2) | Day 0 to Day 85 | 
| PK Measures：CL | Total clearance (CL) | Day 0 to Day 85 | 
| PK Measures：Vd | Apparent volume of distribution (Vd) | Day 0 to Day 85 | 
| Proportions of participants with negative conversion in viral nucleic acid test | Proportions of participants with negative conversion in viral nucleic acid test 7 days and 14 days after administration (performed on each day of the first week after dosing, every other day of the 2nd week, once a week from the 3rd week) | Day 0 to Day 85 | 
| Viral load change from baseline | Viral load change from baseline (performed on each day of the first week after dosing, every other day of the 2nd week, once a week from the 3rd week) | Day 0 to Day 85 | 
| Pulmonary CT（observe by imaging reports to degree of pulmonary inflammation, degree of vitreous fibrosis) | Pulmonary CT changes during the study period | Day 0 to Day 85 |