Clinical trial NCT04780321: JS016 (Anti-SARS-CoV-2 Monoclonal Antibody)With Mild and Moderate COVID-19 or SARS-CoV-2 Asymptomatic Infection Subects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: COVID-19
Lead sponsor: Shanghai Junshi Bioscience Co., Ltd.
Sponsor class: OTHER
First posted: 2021-03-03
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy Measurs(Time to negative conversion in viral nucleic acid test(by RT-PCR) for diagnostic samples)
timeFrame: 0-85days
measure: Safety Measurements : 90 of participants with treatment-related adverse events as assessed byCTCAE v5.0
timeFrame: 0-85days
Secondary outcomes:
measure: PK Measures:AUC0-tau
timeFrame: Day 0 to Day 85
measure: PK Measures：Cmax
timeFrame: Day 0 to Day 85
measure: PK Measures：Tmax
timeFrame: Day 0 to Day 85
measure: PK Measures：t1/2
timeFrame: Day 0 to Day 85
measure: PK Measures：CL
timeFrame: Day 0 to Day 85
measure: PK Measures：Vd
timeFrame: Day 0 to Day 85
measure: Proportions of participants with negative conversion in viral nucleic acid test
timeFrame: Day 0 to Day 85
measure: Viral load change from baseline
timeFrame: Day 0 to Day 85
measure: Pulmonary CT（observe by imaging reports to degree of pulmonary inflammation, degree of vitreous fibrosis)
timeFrame: Day 0 to Day 85
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Ditan Hospital affiliated to Capital Medical University
city: Shanghai
country: China
facility: Huashan Hospital affiliated to Fudan University
Study officials:
References:
citation: 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.