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This is a randomized, double-blind, placebo-controlled, phase I clinical study to evaluate the tolerability, safety, pharmacokinetic profile and immunogenicity of JS016 (anti-SARS-CoV-2 monoclonal antibody) injection in Chinese healthy subjects after intravenous infusion of single dose.Eligible patients will be injection JS016 (anti-SARS-CoV-2 monoclonal antibody)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Test group | Experimental |
| |
| Control group | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JS016 (anti-SARS-CoV-2 monoclonal antibody) | Combination Product | JS016 (anti-SARS-CoV-2 monoclonal antibody) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Correlation of adverse events with the investigational product | Any adverse event, serious adverse event (SAE) occurred during the clinical study, including clinical symptoms and abnormal vital signs, abnormal laboratory tests (complete blood cell count, serum chemistry, routine urinalysis, coagulation function, etc.) and 12-lead ECGs will be observed for all the subjects, the their clinical manifestations and features, severity, time to onset, end time, therapeutic measures and outcomes will be recorded, and the correlation of the adverse events with the investigational product will be judged | 12 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Primary pharmacokinetic variables | Area under the curve from the time of dosing to the last measurable concentration time t (AUC0-last); | 12 Weeks |
| Primary pharmacokinetic variables | Maximum concentration (Cmax); |
| Measure | Description | Time Frame |
|---|---|---|
| pharmacokinetic | Area under the analyte concentration-time curve from time 0 and extrapolated to infinite time (AUC0-∞); | 12 Weeks |
| pharmacokinetic | Time to maximum concentration (Tmax); |
Inclusion Criteria:
Exclusion Criteria:
Excluded for novel coronavirus (SARS-CoV-2) infection
Having one of the following evidence on SARS-CoV-2 infection:
Previous vaccination of SARS-CoV-2 vaccine or having participated in the clinical trial on SARS-CoV-2 neutralizing antibody;
Use of therapeutic biologics within 12 weeks prior to screening, or remaining in the elimination period of the drug (within 5 half-lives) at random administration, whichever is longer;
Participation in any other clinical study with intervention of investigational product within 4 weeks prior to screening, or remaining in the elimination period of the drug (within 5 half-lives) prior to screening, whichever is longer;
Vaccination of vaccine within 12 weeks prior to screening, or plan to use Bacille Calmette-Guérin vaccine or other vaccine during the study and within 12 weeks after the study;
Use of hydroxychloroquine, herbal medicine, any prescription drug or over-the-counter drug within (inclusive) 14 days prior to screening; Surgery
Any major surgery within 8 weeks (inclusive) prior to screening, or requiring such surgery during the study, and such surgery is considered by the investigator to possibly bring unacceptable risk for subjects upon confirmation with the sponsor; Abnormal physical examination, laboratory examination and history
Lying systolic blood pressure (SBP) > 140 mmHg or < 90 mmHg, and/or diastolic blood pressure (DBP) > 90 mmHg or < 50 mmHg at screening and randomization;
Total white blood cell (WBC) count < 3.5 x 109/L, platelet < 140 x 109/L, neutrophil < 2.0 x 109/L, or hemoglobin decreased (male < 135 g/L, female < 120 g/L), lymphocytes < 1.0 x 109/L at screening;
ALT or AST > 2 × upper limit of normal, or eGFR ≤ 90 mL/min/1.73m2 at screening;
Abnormal ECG at screening, single QTcF > 450 msec, and/or other abnormalities of clinical significance, unacceptable risk that may be brought by participation in the study;
History of HIV infection, and/or positive aiti-HIV antibody, positive hepatitis B surface antigen (HBsAg), positive hepatitis C antibody (anti-HCV), or positivetreponema pallidum particle agglutination test (TPPA) at screening;
History of transplantation of vital organs (e.g., heart, lung, liver, kidney, etc.);
Having malignant tumor (excluding the malignant tumor cured with no recurrence in the past 5 years, completely resected basal cell and squamous cell carcinoma of skin, completely resected carcinoma in situ of any type);
Other major diseases within one year;
Medical history and previous history suggest the following diseases: including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, oncological, pulmonary, immune, mental or cerebro- and cardiovascular diseases; Substance abuse, alcohol abuse
History of drug abuse or use of narcotics in the past 5 years, or positive urine drug screening;
History of alcohol abuse or intake of excessive alcohol in the past 6 months (14 units of alcohol per week: 1 unit = 285 mL beer, or 25 mL liquor, or 100 mL wine), or alcohol test positive; History of allergies
Known serious allergic reaction or hypersensitive to food, inhaled and contact material as well as drugs, or allergic constitution (allergy to various drugs and food);
Known history of allergy or hypersensitivity to the investigational drug, other monoclonal antibody drugs and therapeutic protein preparations (fresh or frozen plasma, human serum albumin, cytokine, interleukin etc.); Pregnancy, lactation
Positive β-Human Chorionic Gonadotropin (β-HCG) or breastfeeding female subjects; Blood loss and others
Subjects who lost blood or donated more than 400 mL, or received blood transfusion in the past 3 months; or plan to donate blood during the study;
Any other condition that the subject is considered by the investigator as inappropriate to participate in the study, for example, potential compliance issue, inability to complete all the tests and evaluations according to the requirements in the protocol, or uncontrolled mental, neurological or psychological disorders, participation in the study is judged by the investigator to be associated with uncontrollable risk.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jing Zhang | Contact | 021-52888189 | 13816357098@163.com | |
| Wenhong Zhang | Contact | 021-52888123 | zhangwenhong@fudan.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Huashan Hospital affiliated to Fudan University | Recruiting | Shanghai | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34473343 | Derived | 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. | |
| 33972256 |
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| 12 Weeks |
| Primary pharmacokinetic variables | Mean residence time (MRT) | 12 Weeks |
| Primary pharmacokinetic variables | Terminal half life (t1/2); | 12 Weeks |
| 12 Weeks |
| pharmacokinetic | Clearance (CL); | 12 Weeks |
| pharmacokinetic | Apparent terminal elimination rate constant (λz) | 12 Weeks |
| pharmacokinetic | Apparent volume of distribution (Vd) | 12 Weeks |
| Wu X, Li N, Wang G, Liu W, Yu J, Cao G, Wang J, Chen Y, Ma J, Wu J, Yang H, Mao X, He J, Yu Y, Qiu C, Li N, Yao S, Feng H, Yan J, Zhang W, Zhang J. Tolerability, Safety, Pharmacokinetics, and Immunogenicity of a Novel SARS-CoV-2 Neutralizing Antibody, Etesevimab, in Chinese Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled, First-in-Human Phase 1 Study. Antimicrob Agents Chemother. 2021 Jul 16;65(8):e0035021. doi: 10.1128/AAC.00350-21. Epub 2021 Jul 16. |
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C000711968 | etesevimab |
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