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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Biological: Recombinant Human Anti-SARS-CoV-2 Monoclonal Antibody(25mg/kg;50mg/kg;100mg/kg); Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100010
    • Beijing Ditan Hospital Affiliated to Capital Medical University
  • Shanghai, China
    • Huashan Hospital Affiliated to Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age of 18-65 years (inclusive) ,women or man
2. SARS-CoV-2 detected in the diagnostic specimen (nasopharyngeal swab)
3. High homology of viral gene sequencing with the known SARS-CoV-2."
4. Mild/moderateillness COVID-19 or SARS-CoV-2 asymptomatic infection
5. 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
6. No plan of pregnancy and being willing to use effective contraceptive measures
7. Signed the informed consent form, sufficiently understanding of the content

Exclusion Criteria:

1. positive IgM/IgG against SARS-CoV-2 prior to randomization.
2. Severeor critical illness
3. Uncontrolled hypertension, cardiovascular/cerebrovascular diseases,lung diseases
4. Type 1 diabetes, or newly diagnosed or poorly controlled type 2 diabetes
5. Liver and kidney dysfunction, immune or inflammatory diseases, infections, surgery, tumors, and other major diseases
6. History of SARS-CoV-2 vaccination or participation in clinical trial with neutralizing antibody against SARS-CoV-2.
7. 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
8. 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
9. Platelets and hemoglobin test results during screening period are abnormal and have clinical significanc.
10. Anaphylaxis, urine drug screening, alcohol dependence, lactation during pregnancy, blood loss, and others

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Anti-SARS-CoV-2 Monoclonal Antibody dose 1/2/3; 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); use dose 1/2/3 60 patients receipt JS016 intravenous infusion on day 1
PLACEBO_COMPARATOR: Placebo; use placebo to treat COVID-19	Drug: Placebo; 30 patients receipt placebo intravenous infusion on day 1

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

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Publications and helpful links

General Publications

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 30, 2020
• Primary Completion (ACTUAL): August 31, 2021
• Study Completion (ACTUAL): August 31, 2021

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: March 2, 2021
• First Posted (ACTUAL): March 3, 2021

Study Record Updates

• Last Update Posted (ACTUAL): July 18, 2022
• Last Update Submitted That Met QC Criteria: July 14, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Asymptomatic Diseases; COVID-19; Asymptomatic Infections; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: JS016-002-Ib/II

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No