Clinical trial NCT04441918: Tolerability,Safety,Pharmacokinetic Profile and Immunogenicity of a Recombinant Humanized Anti-SARS-CoV-2 Monoclonal Antibody (JS016) for Injection in Chinese Health Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: COVID-19; and High Infection Risk of SARS-CoV-2
Lead sponsor: Shanghai Junshi Bioscience Co., Ltd.
Sponsor class: OTHER
First posted: 2020-06-22
Enrollment: 40
Sex: ALL
Minimum age (years): 15
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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)


Eligibility criteria: 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.

Primary outcomes:
measure: Correlation of adverse events with the investigational product
timeFrame: 12 Weeks
Secondary outcomes:
measure: Primary pharmacokinetic variables
timeFrame: 12 Weeks
measure: Primary pharmacokinetic variables
timeFrame: 12 Weeks
measure: Primary pharmacokinetic variables
timeFrame: 12 Weeks
measure: Primary pharmacokinetic variables
timeFrame: 12 Weeks
Other outcomes:
measure: pharmacokinetic
timeFrame: 12 Weeks
measure: pharmacokinetic
timeFrame: 12 Weeks
measure: pharmacokinetic
timeFrame: 12 Weeks
measure: pharmacokinetic
timeFrame: 12 Weeks
measure: pharmacokinetic
timeFrame: 12 Weeks
Locations:
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.
citation: 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.