A Phase Ia Clinical Study to Evaluate the Safety, Tolerability, PK and Immunogenicity of YBSW015 in Healthy Subjects
Primary Purpose
Coronavirus Disease 2019
Status
Not yet recruiting
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
YBSW015 injection
Sponsored by
About this trial
This is an interventional other trial for Coronavirus Disease 2019
Eligibility Criteria
Inclusion Criteria:
- Aged ≥ 18 years and ≤ 55 years at screening, regardless of gender;
- Body weight ≥50kg for males and ≥45kg for females, body mass index (BMI) between 18.0 kg/m2and 30.0 kg/m2 (inclusive) at screening;
- Subject who has negative result in the YBSW015 serology test in screening;
- Has completed COVID-19 vaccination and the last dose more than 6 weeks prior to randomization
- Subject who are normal in the physical examination, vital signs, laboratory tests and other auxiliary examinations (chest radiograph, abdominal ultrasound scan, 12-lead ECG, etc.), or abnormal without clinical significance as judged by the investigator;
- Subject who has a negative result in the urine human chorionic gonadotropin test in screening period, and a negative result in the blood human chorionic gonadotropin test in baseline period;
- Subjects (including their partners) who do not have a pregnancy plan and are willing to adopt effective contraception measures from signing the informed consent to 6 months after administration of the investigational drug;
- Subjects who has understood the trial feature, significance, possible benefits, possible inconveniences and potential risks and discomforts in detail, and are willing to participate in this clinical trial and are able to communicate well with the investigator and follow the requirements of the entire study, and has signed the written informed consent form prior to the trial.
Exclusion Criteria:
- The positive results are obtained in SARS-CoV-2 nucleic acid test using nasal swabs prior to screening and randomization (results within 7 days prior to randomization);
- Has recent SARS-CoV-2 infection that resolved within 6 weeks prior to randomization;
- Those who have received any SARS-CoV-2 immunoglobulin, plasma from COVID-19 survivors in recovery period(within 15 weeks);
- Those who have used therapeutic biologics within 12 weeks before screening, or those who are in drug elimination period currently (within 5 half-lives), whichever is longer;
- Those who have participated in clinical study of other intervention investigational products within 12 weeks prior to screening, or those who are in drug elimination period currently (within 5 half-lives), whichever is longer;
- Those who have been vaccinated against pathogens other than SARS CoV-2 within 6 weeks prior to screening, or plan to be vaccinated against pathogens other than SARS CoV-2 during the study or within 6 weeks after the study;
- Those who have taken herbal medicines, dietary supplements (excluding vitamin, mineral and trace element supplements), or any prescription or non-prescription drugs within 14 days (inclusive) prior to screening;
- Those who have had major surgery history within 8 weeks (including 8 weeks) before screening, or plan to perform surgeries during the study, and those who are exposed to unacceptable risks brought by such surgery at the discretion of the sponsor and the investigator;
- Those who have an abnormal electrocardiogram with clinical significance at screening, or QTc> 450 msec, or other abnormal electrocardiogram data with clinical significance;
- Subjects with poor blood pressure control (systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg);
- Positive serology test results for hepatitis C virus antibody, human immunodeficiency virus antibody, Syphilis Treponema Pallidum antibody (S-TP) and hepatitis B virus surface antigen (HBsAg) at Screening;
- Those who have a history of transplantation in vital organs (such as heart, lung, liver and kidney);
- Patients with malignant tumors (excluding those whose malignant tumors have been cured with no recurrence in recent 5 years, with complete excision of skin basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of any type);
- Those who have cardiovascular diseases, respiratory diseases, gastrointestinal diseases, endocrine system diseases, hematological system diseases or nervous system diseases, and are exposed to higher risks by taking the investigational drug, or those whose disease state can obviously change absorption, distribution, metabolism or excretion of the investigational drug;
- Those who have a history of drug abuse or drug taking within 5 years prior to screening or have a positive result in urine drug test;
- Those who have a history of alcoholism or excessive drinking (14 units of alcohol per week :1 unit = 285 mL beer, or 25 mL liquor, or 100 mL wine) within 6 months prior to screening or have a positive result in alcohol breath test;
- Those who smoke ≥5 cigarettes per day within 6 months prior to screening, or are unwilling/unable to stop nicotine intake during the study;
- Those who are known to be allergic to the investigational drug, monoclonal antibody drug, therapeutic protein preparation, human serum albumin, cytokines, interleukin etc. or have a history of or a propensity to allergy;
- Females with a positive result of pregnancy test and lactating females;
- Those who have a blood loss or donation of greater than 400 mL, or received blood transfusion or blood products within the past 3 months, or plan to donate blood during the study;
- Those with a history of needle sickness, hemophobia or intolerance of venipunctures;
- Subjects who cannot complete the study due to other reasons or are supposed to be excluded at the discretion of the investigator.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
YBSW015 injection 180mg
YBSW015 injection 450mg
YBSW015 injection 900mg
YBSW015 injection 1800mg
Arm Description
Outcomes
Primary Outcome Measures
safety of YBSW015 injection
Evaluation of treatment-emergent adverse event (TEAE) and serious adverse events (SAE) during treatment;
tolerability of YBSW015 injection
Evaluation of local tolerance: administration site reaction;
Secondary Outcome Measures
PK parameter
Peak concentration (Cmax) Immunogenicity: To detect the positive rate and titer of anti-drug antibody ADA
PK parameter
peak time (Tmax)
PK parameter
terminal elimination rate constant (λz)
PK parameter
terminal elimination half-life (t1/2)
PK parameter
area under the curve from time zero to the time of the last time of quantifiable concentration (AUC0-t)
PK parameter
area under the concentration-time curve from time zero to infinite time (AUC0-∞)
PK parameter
extrapolated percentage of AUC0-∞ (%AUCex)
PK parameter
apparent clearance (CLz)
PK parameter
apparent volume of distribution (Vz)
PK parameter
mean residence time (MRT)
Immunogenicity
positive rate of anti-drug antibody ADA
Immunogenicity
Titer of anti-drug antibody ADA
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05369754
Brief Title
A Phase Ia Clinical Study to Evaluate the Safety, Tolerability, PK and Immunogenicity of YBSW015 in Healthy Subjects
Official Title
A Randomized, Double-blind, Placebo-controlled, Dose-escalation Phase Ia Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of YBSW015 Injection in Healthy Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 2022 (Anticipated)
Primary Completion Date
January 2023 (Anticipated)
Study Completion Date
February 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yabao Pharmaceutical Group
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This is phase Ia study to research YBSW015 injection which is a monomolecular bispecific antibody. The Primary objective is to evaluate the safety and tolerability of YBSW015 injection after a single intravenous injection at different doses in healthy subjects.
The Secondary objective is to evaluate the pharmacokinetic characteristics and immunogenicity of different doses of YBSW015 injection after a single intravenous injection in healthy subjects. This study is a single-center, randomized, double-blind, placebo-controlled, single-dose escalation clinical trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus Disease 2019
7. Study Design
Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
YBSW015 injection 180mg
Arm Type
Experimental
Arm Title
YBSW015 injection 450mg
Arm Type
Experimental
Arm Title
YBSW015 injection 900mg
Arm Type
Experimental
Arm Title
YBSW015 injection 1800mg
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
YBSW015 injection
Intervention Description
Prepared YBSW015 injection is intravenously injected by an infusion pump or gravity infusion with intravenous infusion of 250 mL for 60 min±10 min.
Primary Outcome Measure Information:
Title
safety of YBSW015 injection
Description
Evaluation of treatment-emergent adverse event (TEAE) and serious adverse events (SAE) during treatment;
Time Frame
from screening visit to the end of the follow-up period, assessed up to 85 days
Title
tolerability of YBSW015 injection
Description
Evaluation of local tolerance: administration site reaction;
Time Frame
from screening visit to the end of the follow-up period, assessed up to 85 days
Secondary Outcome Measure Information:
Title
PK parameter
Description
Peak concentration (Cmax) Immunogenicity: To detect the positive rate and titer of anti-drug antibody ADA
Time Frame
from screening visit to the end of follow-up period, assessed up to 85 days
Title
PK parameter
Description
peak time (Tmax)
Time Frame
from screening visit to the end of follow-up period, assessed up to 85 days
Title
PK parameter
Description
terminal elimination rate constant (λz)
Time Frame
from screening visit to the end of follow-up period, assessed up to 85 days
Title
PK parameter
Description
terminal elimination half-life (t1/2)
Time Frame
from screening visit to the end of follow-up period, assessed up to 85 days
Title
PK parameter
Description
area under the curve from time zero to the time of the last time of quantifiable concentration (AUC0-t)
Time Frame
from screening visit to the end of follow-up period, assessed up to 85 days
Title
PK parameter
Description
area under the concentration-time curve from time zero to infinite time (AUC0-∞)
Time Frame
from screening visit to the end of follow-up period, assessed up to 85 days
Title
PK parameter
Description
extrapolated percentage of AUC0-∞ (%AUCex)
Time Frame
from screening visit to the end of follow-up period, assessed up to 85 days
Title
PK parameter
Description
apparent clearance (CLz)
Time Frame
from screening visit to the end of follow-up period, assessed up to 85 days
Title
PK parameter
Description
apparent volume of distribution (Vz)
Time Frame
from screening visit to the end of follow-up period, assessed up to 85 days
Title
PK parameter
Description
mean residence time (MRT)
Time Frame
from screening visit to the end of follow-up period, assessed up to 85 days
Title
Immunogenicity
Description
positive rate of anti-drug antibody ADA
Time Frame
from screening visit to the end of follow-up period, assessed up to 85 days
Title
Immunogenicity
Description
Titer of anti-drug antibody ADA
Time Frame
from screening visit to the end of follow-up period, assessed up to 85 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Aged ≥ 18 years and ≤ 55 years at screening, regardless of gender;
Body weight ≥50kg for males and ≥45kg for females, body mass index (BMI) between 18.0 kg/m2and 30.0 kg/m2 (inclusive) at screening;
Subject who has negative result in the YBSW015 serology test in screening;
Has completed COVID-19 vaccination and the last dose more than 6 weeks prior to randomization
Subject who are normal in the physical examination, vital signs, laboratory tests and other auxiliary examinations (chest radiograph, abdominal ultrasound scan, 12-lead ECG, etc.), or abnormal without clinical significance as judged by the investigator;
Subject who has a negative result in the urine human chorionic gonadotropin test in screening period, and a negative result in the blood human chorionic gonadotropin test in baseline period;
Subjects (including their partners) who do not have a pregnancy plan and are willing to adopt effective contraception measures from signing the informed consent to 6 months after administration of the investigational drug;
Subjects who has understood the trial feature, significance, possible benefits, possible inconveniences and potential risks and discomforts in detail, and are willing to participate in this clinical trial and are able to communicate well with the investigator and follow the requirements of the entire study, and has signed the written informed consent form prior to the trial.
Exclusion Criteria:
The positive results are obtained in SARS-CoV-2 nucleic acid test using nasal swabs prior to screening and randomization (results within 7 days prior to randomization);
Has recent SARS-CoV-2 infection that resolved within 6 weeks prior to randomization;
Those who have received any SARS-CoV-2 immunoglobulin, plasma from COVID-19 survivors in recovery period(within 15 weeks);
Those who have used therapeutic biologics within 12 weeks before screening, or those who are in drug elimination period currently (within 5 half-lives), whichever is longer;
Those who have participated in clinical study of other intervention investigational products within 12 weeks prior to screening, or those who are in drug elimination period currently (within 5 half-lives), whichever is longer;
Those who have been vaccinated against pathogens other than SARS CoV-2 within 6 weeks prior to screening, or plan to be vaccinated against pathogens other than SARS CoV-2 during the study or within 6 weeks after the study;
Those who have taken herbal medicines, dietary supplements (excluding vitamin, mineral and trace element supplements), or any prescription or non-prescription drugs within 14 days (inclusive) prior to screening;
Those who have had major surgery history within 8 weeks (including 8 weeks) before screening, or plan to perform surgeries during the study, and those who are exposed to unacceptable risks brought by such surgery at the discretion of the sponsor and the investigator;
Those who have an abnormal electrocardiogram with clinical significance at screening, or QTc> 450 msec, or other abnormal electrocardiogram data with clinical significance;
Subjects with poor blood pressure control (systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg);
Positive serology test results for hepatitis C virus antibody, human immunodeficiency virus antibody, Syphilis Treponema Pallidum antibody (S-TP) and hepatitis B virus surface antigen (HBsAg) at Screening;
Those who have a history of transplantation in vital organs (such as heart, lung, liver and kidney);
Patients with malignant tumors (excluding those whose malignant tumors have been cured with no recurrence in recent 5 years, with complete excision of skin basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of any type);
Those who have cardiovascular diseases, respiratory diseases, gastrointestinal diseases, endocrine system diseases, hematological system diseases or nervous system diseases, and are exposed to higher risks by taking the investigational drug, or those whose disease state can obviously change absorption, distribution, metabolism or excretion of the investigational drug;
Those who have a history of drug abuse or drug taking within 5 years prior to screening or have a positive result in urine drug test;
Those who have a history of alcoholism or excessive drinking (14 units of alcohol per week :1 unit = 285 mL beer, or 25 mL liquor, or 100 mL wine) within 6 months prior to screening or have a positive result in alcohol breath test;
Those who smoke ≥5 cigarettes per day within 6 months prior to screening, or are unwilling/unable to stop nicotine intake during the study;
Those who are known to be allergic to the investigational drug, monoclonal antibody drug, therapeutic protein preparation, human serum albumin, cytokines, interleukin etc. or have a history of or a propensity to allergy;
Females with a positive result of pregnancy test and lactating females;
Those who have a blood loss or donation of greater than 400 mL, or received blood transfusion or blood products within the past 3 months, or plan to donate blood during the study;
Those with a history of needle sickness, hemophobia or intolerance of venipunctures;
Subjects who cannot complete the study due to other reasons or are supposed to be excluded at the discretion of the investigator.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase Ia Clinical Study to Evaluate the Safety, Tolerability, PK and Immunogenicity of YBSW015 in Healthy Subjects
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