A Randomized, Double-blind, Placebo-controlled Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics Characteristics and Primary Efficacy of HS-10517 in Chinese Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- HS-10517 Dose 4
- Conditions
- COVID-19
- Sponsor
- Jiangsu Hansoh Pharmaceutical Co., Ltd.
- Enrollment
- 340
- Locations
- 1
- Primary Endpoint
- The incidence and severity of adverse events (AE), serious adverse events (SAE) and adverse events leading to withdrawal from the trial and the correlation with the investigational drug in single ascending dose (SAD)
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
A Phase I/II, randomized, double-blind, placebo-controlled study to evaluate safety, tolerability, pharmacokinetics and primary efficacy of HS-10517 in Chinese adult participants.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Inclusion Criteria for SAD, MAD and SE：
- •Subjects should fully understand the content, process and possible adverse reactions of the study, and voluntarily sign the informed consent form;
- •The age at the time of signing the informed consent is between 18 and 45 years old (including the critical value)
- •Subjects with negative COVID-19 nucleic acid detection in screening period;
- •The body mass index (BMI=body weight \[kg\]/height2 \[m2\]) at screening is 19\~27kg/m2 (including the critical value), and the weight of men is ≥ 50kg, and that of women is ≥ 40kg;
- •The blood pregnancy test of female subjects in the screening period and the baseline period is negative;
- •Female subjects must agree to take effective contraceptive measures from the date of signing the informed consent form to 30 days after the last administration:
- •Those with fertility: from the date of signing the informed consent form to 30 days after the last administration, ① avoid pregnancy, ② if having sex with the opposite sex, agree to continue to use one or more forms of effective contraception (such as verified intrauterine devices, bilateral tubal ligation or correct use of condoms, excluding any form of hormonal contraceptives). If the male partner has undergone an effective sterilization operation, additional effective contraception measures should be taken when the sperm is uncertain);
- •Non-fertility: ① Postmenopausal (spontaneous amenorrhea ≥ 12 months, or spontaneous amenorrhea ≥ 6 months and FSH\>40 IU/L, without other obvious pathological or physiological reasons) before screening; Or ② documented surgical sterilization (such as hysterectomy, bilateral salpingectomy or bilateral oophorectomy, etc.);
- •Male subjects (including their female partners) must agree to take effective contraceptive measures from the date of signing the informed consent form to 30 days after the last administration:
Exclusion Criteria
- Not provided
Arms & Interventions
HS-10517 Dose 4
Dose level 1 of HS-10517 Tablets，Dose 4
Intervention: HS-10517 Dose 4
HS-10517 Dose 1
Dose level 1 of HS-10517 Tablets，Dose 1
Intervention: HS-10517 Dose 1
HS-10517 Dose 2
Dose level 1 of HS-10517 Tablets，Dose 2
Intervention: HS-10517 Dose 2
HS-10517 Dose 3
Dose level 1 of HS-10517 Tablets，Dose 3
Intervention: HS-10517 Dose 3
Placebo Comparator
Dose level A of placebo
Intervention: Placebo
Outcomes
Primary Outcomes
The incidence and severity of adverse events (AE), serious adverse events (SAE) and adverse events leading to withdrawal from the trial and the correlation with the investigational drug in single ascending dose (SAD)
Time Frame: Day 1 to Day 5
The definition of adverse event \[AE\] is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The definition of serious adverse event \[SAE\] is any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect.
Number of participants with clinically significant change from baseline in vital signs in SAD
Time Frame: Day 1 to Day 5
Number of participants with clinically significant change from baseline in 12-lead electrocardiogram (ECG) findings in SAD
Time Frame: Day 1 to Day 5
Criteria for clinically significant changes in 12-lead ECG are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is \>450 msec; or an absolute QTc value is ≥500 msec for any scheduled 12-lead ECG.
Number of participants with clinically significant abnormalities in laboratory examination in SAD
Time Frame: Day 1 to Day 5
Number of participants with clinically significant abnormalities in physical examination in SAD
Time Frame: Day 1 to Day 5
The incidence and severity of adverse events (AE), serious adverse events (SAE) and adverse events leading to withdrawal from the trial and the correlation with the investigational drug in multiple ascending dose (MAD)
Time Frame: Day 1 to Day 14
The definition of adverse event \[AE\] is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The definition of serious adverse event \[SAE\] is any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect.
Number of participants with clinically significant change from baseline in vital signs in MAD
Time Frame: Day 1 to Day 14
Number of participants with clinically significant change from baseline in 12-lead electrocardiogram (ECG) findings in MAD
Time Frame: Day 1 to Day 14
Criteria for clinically significant changes in 12-lead ECG are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is \>450 msec; or an absolute QTc value is ≥500 msec for any scheduled 12-lead ECG.
Number of participants with clinically significant abnormalities in laboratory examination in MAD
Time Frame: Day 1 to Day 14
Number of participants with clinically significant abnormalities in physical examination in MAD
Time Frame: Day 1 to Day 14
The incidence and severity of adverse events (AE), serious adverse events (SAE) and adverse events leading to withdrawal from the trial and the correlation with the investigational drug in supratherapeutic exposure (SE)
Time Frame: Day 1 to Day 13
The definition of adverse event \[AE\] is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The definition of serious adverse event \[SAE\] is any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect.
Number of participants with clinically significant change from baseline in vital signs in SE
Time Frame: Day 1 to Day 13
Number of participants with clinically significant change from baseline in 12-lead electrocardiogram (ECG) findings in SE
Time Frame: Day 1 to Day 13
Criteria for clinically significant changes in 12-lead ECG are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is \>450 msec; or an absolute QTc value is ≥500 msec for any scheduled 12-lead ECG.
Number of participants with clinically significant abnormalities in laboratory examination in SE
Time Frame: Day 1 to Day 13
Number of participants with clinically significant abnormalities in physical examination in SE
Time Frame: Day 1 to Day 13
Percentage of participants with a negative RT-PCR test through day 5-modified intent-to-treat (mITT) population.
Time Frame: Day 1 to Day 5
Secondary Outcomes
- Apparent clearance at steady state (CLss/F) in last dose of MAD(Day 1 to Day 14)
- Area under the concentration time profile in one dosing interval at steady state (AUCss) in last dose of MAD(Day 1 to Day 14)
- Maximum plasma concentration (Cmax) in SAD(Day 1 to Day 5)
- Time for Cmax (tmax) in SAD(Day 1 to Day 5)
- Area under the concentration time profile from time 0 to the time of last quantifiable plasma concentration (AUC0-last) in SAD(Day 1 to Day 5)
- Area under the concentration time profile from time 0 to infinity (AUC0-inf) in SAD(Day 1 to Day 5)
- Terminal rate constant (λz) in SAD(Day 1 to Day 5)
- Terminal half-life (t1/2) in SAD(Day 1 to Day 5)
- Apparent clearance (CL/F) in SAD(Day 1 to Day 5)
- Apparent volume of distribution (Vd/F) in SAD(Day 1 to Day 5)
- Mean residence time (MRT) in SAD symptoms to the sustained clinical resolution within 28 days（Phase II）(Day 1 to Day 5)
- Maximum plasma concentration (Cmax) in first dose of MAD(Day 1 to Day 14)
- Time for Cmax (tmax) in first dose of MAD(Day 1 to Day 14)
- Area under the concentration time profile from time 0 to 24 hours in first dose of MAD(Day 1 to Day 14)
- Area under the concentration time profile from time 0 to 12 hours in first dose of MAD(Day 1 to Day 14)
- Maximum plasma concentration at steady state (Css,max) in last dose of MAD(Day 1 to Day 14)
- Time for Cmax at steady state (tss,max) in last dose of MAD(Day 1 to Day 14)
- Minimum plasma concentration at steady state (Css,min) in last dose of MAD(Day 1 to Day 14)
- Degree of accumulation after multiple doses (RAC, including RAUC and RCmax) in last dose of MAD(Day 1 to Day 14)
- Maximum plasma concentration (Cmax) in SE(Day 1 to Day 13)
- Time for Cmax (tmax) in SE(Day 1 to Day 13)
- Area under the concentration time profile from time 0 to the time of last quantifiable plasma concentration (AUC0-last) in SE(Day 1 to Day 13)
- Area under the concentration time profile from time 0 to infinity (AUC0-inf) in SE(Day 1 to Day 13)
- Terminal rate constant (λz) in SE(Day 1 to Day 13)
- Terminal half-life (t1/2) in SE(Day 1 to Day 13)
- Apparent clearance (CL/F) in SE(Day 1 to Day 13)
- Apparent volume of distribution (Vd/F) in SE(Day 1 to Day 13)
- Mean residence time (MRT) in SE(Day 1 to Day 13)
- Time to sustained resolution of 11 COVID-19 symptoms within 28 days(Day 1 to Day 28)
- Change of viral load over time compared to baseline(Day 1 to Day 28)
- Time to the first negative RT-PCR test(Day 1 to Day 28)
- Virological response at each time point after randomization(Day 1 to Day 28)
- Time to sustained alleviation of 11 targeted COVID-19 signs/symptoms within 28 days(Day 1 to Day 28)
- Time to sustained resolution of each targeted COVID-19 symptom(Day 1 to Day 28)
- Change of the score of each COVID-19 symptom(Day 1 to Day 28)
- Proportion of severe cases within 28 days(Day 1 to Day 28)
- The plasma concentration of HS-10517 in COVID-19 patients in phase II study(Day 1 to Day 7)
- Population apparent clearance (CL/F) of COVID-19 patients in phase II study(Day 1 to Day 7)
- Population apparent volume of distribution (Vd/F) of COVID-19 patients in phase II study(Day 1 to Day 7)