Tolerability,Safety,Pharmacokinetic Profile and Immunogenicity of a Recombinant Humanized Anti-SARS-CoV-2 Monoclonal Antibody (JS016) for Injection in Chinese Health Subjects

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

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)

Study Overview

• Status: Unknown
• Conditions: COVID-19; and High Infection Risk of SARS-CoV-2
• Intervention / Treatment: Combination product: JS016 (anti-SARS-CoV-2 monoclonal antibody)

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jing Zhang; Phone Number: 021-52888189; Email: 13816357098@163.com
• Study Contact Backup: Name: Wenhong Zhang; Phone Number: 021-52888123; Email: zhangwenhong@fudan.edu.cn

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Huashan Hospital affiliated to Fudan University
    • Contact: Jing Zhang; Phone Number: 02152888189 02152888189; Email: 13816357098@163.com
    • Contact: Wenhong Zhang; Phone Number: 02152888123 02152888123; Email: zhangwenhong@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female subjects aged 18 to 45 years, inclusive;
2. The body weight no less than 50 kg for male subjects and no less than 45 kg for female subjects. Body mass index (BMI) = weight (kg)/square of height (m2), ranging from 18-28 kg/m2 (including the critical value);
3. Normal or abnormal but clinically insignificant physical examination, vital signs, laboratory tests and other accessory examinations (chest radiology, abdominal B-mode ultrasonography, ECG, etc.);
4. No plan of pregnancy and being willing to use effective contraceptive measures for subject (including partner) from informed consent to 6 months after administration of investigational product, see Appendix 5 for the specific contraceptive measures;
5. The subjects are able to understand the content of the study and voluntary to sign the informed consent form; meanwhile, being able to complete the study as required in the protocol.

Exclusion Criteria:

Excluded for novel coronavirus (SARS-CoV-2) infection

1. Having one of the following evidence on SARS-CoV-2 infection:

   1. SARS-CoV-2 determined by reverse transcription-polymerase chain reaction (RT-PCR) and/or next generation sequencing (NGS) in diagnostic specimens (nasopharyngeal swabs) during screening and pre-randomization (results within 3 days before randomization are accepted);
   2. Previous viral gene sequencing showed high homology with the known SARS-CoV-2;
   3. Positive specific antibody IgM or IgG against serum SARS-CoV-2; Excluded for previous and concomitant medications
2. Previous vaccination of SARS-CoV-2 vaccine or having participated in the clinical trial on SARS-CoV-2 neutralizing antibody;
3. 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;
4. 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;
5. 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;
6. Use of hydroxychloroquine, herbal medicine, any prescription drug or over-the-counter drug within (inclusive) 14 days prior to screening; Surgery
7. 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
8. 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;
9. 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;
10. ALT or AST > 2 × upper limit of normal, or eGFR ≤ 90 mL/min/1.73m2 at screening;
11. 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;
12. 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;
13. History of transplantation of vital organs (e.g., heart, lung, liver, kidney, etc.);
14. 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);
15. Other major diseases within one year;
16. 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
17. History of drug abuse or use of narcotics in the past 5 years, or positive urine drug screening;
18. 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
19. 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);
20. 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
21. Positive β-Human Chorionic Gonadotropin (β-HCG) or breastfeeding female subjects; Blood loss and others
22. 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;
23. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control group	Combination product: JS016 (anti-SARS-CoV-2 monoclonal antibody); JS016 (anti-SARS-CoV-2 monoclonal antibody)
Experimental: Test group	Combination product: JS016 (anti-SARS-CoV-2 monoclonal antibody); JS016 (anti-SARS-CoV-2 monoclonal antibody)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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);	12 Weeks
Primary pharmacokinetic variables	Mean residence time (MRT)	12 Weeks
Primary pharmacokinetic variables	Terminal half life (t1/2);	12 Weeks

Other Outcome Measures

Outcome Measure	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);	12 Weeks
pharmacokinetic	Clearance (CL);	12 Weeks
pharmacokinetic	Apparent terminal elimination rate constant (λz)	12 Weeks
pharmacokinetic	Apparent volume of distribution (Vd)	12 Weeks

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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2020
• Primary Completion (Anticipated): December 11, 2020
• Study Completion (Anticipated): December 11, 2020

Study Registration Dates

• First Submitted: June 6, 2020
• First Submitted That Met QC Criteria: June 18, 2020
• First Posted (Actual): June 22, 2020

Study Record Updates

• Last Update Posted (Actual): June 22, 2020
• Last Update Submitted That Met QC Criteria: June 18, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: JS016-001-I

Drug and device information, study documents

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