Study of HS-10517 in Chinese Adult Participants

NCT05779579 | Unknown Phase 1

• 1 other identifier: HS-10517-101
• Study Type: interventional
• Target: 340
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19

Keywords

HS-10517; 3CL protease inhibitor; single ascending dose; multiple ascending dose; phase 2 study; dose exploration; Chinese; COVID-19

Outcome Measures

Primary Outcomes (16)

• 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)

  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.

  Day 1 to Day 5

• Number of participants with clinically significant change from baseline in vital signs in SAD

  Day 1 to Day 5

• Number of participants with clinically significant change from baseline in 12-lead electrocardiogram (ECG) findings in SAD

  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.

  Day 1 to Day 5

• Number of participants with clinically significant abnormalities in laboratory examination in SAD

  Day 1 to Day 5

• Number of participants with clinically significant abnormalities in physical examination in SAD

  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)

  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.

  Day 1 to Day 14

• Number of participants with clinically significant change from baseline in vital signs in MAD

  Day 1 to Day 14

• Number of participants with clinically significant change from baseline in 12-lead electrocardiogram (ECG) findings in MAD

  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.

  Day 1 to Day 14

• Number of participants with clinically significant abnormalities in laboratory examination in MAD

  Day 1 to Day 14

• Number of participants with clinically significant abnormalities in physical examination in MAD

  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)

  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.

  Day 1 to Day 13

• Number of participants with clinically significant change from baseline in vital signs in SE

  Day 1 to Day 13

• Number of participants with clinically significant change from baseline in 12-lead electrocardiogram (ECG) findings in SE

  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.

  Day 1 to Day 13

• Number of participants with clinically significant abnormalities in laboratory examination in SE

  Day 1 to Day 13

• Number of participants with clinically significant abnormalities in physical examination in SE

  Day 1 to Day 13

• Percentage of participants with a negative RT-PCR test through day 5-modified intent-to-treat (mITT) population.

  Day 1 to Day 5

Secondary Outcomes (39)

• 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

Study Arms (5)

HS-10517 Dose 1

EXPERIMENTAL

Dose level 1 of HS-10517 Tablets，Dose 1

Drug: HS-10517 Dose 1

HS-10517 Dose 2

EXPERIMENTAL

Dose level 1 of HS-10517 Tablets，Dose 2

Drug: HS-10517 Dose 2

HS-10517 Dose 3

EXPERIMENTAL

Dose level 1 of HS-10517 Tablets，Dose 3

Drug: HS-10517 Dose 3

HS-10517 Dose 4

EXPERIMENTAL

Dose level 1 of HS-10517 Tablets，Dose 4

Drug: HS-10517 Dose 4

Placebo Comparator

EXPERIMENTAL

Dose level A of placebo

Drug: Placebo

Interventions

HS-10517 Dose 1 DRUG

HS-10517 Dose 1+Ritonavir

HS-10517 Dose 1

HS-10517 Dose 2 DRUG

HS-10517 Dose 2+Ritonavir

HS-10517 Dose 2

HS-10517 Dose 3 DRUG

HS-10517 Dose 3+Ritonavir

HS-10517 Dose 3

HS-10517 Dose 4 DRUG

HS-10517 Dose 4+Ritonavir

HS-10517 Dose 4

Placebo DRUG

Dose level A of placebo

Placebo Comparator

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• Those who are fertile must agree to use condoms correctly. If their female partners are women of child-bearing age and have fertility (have not undergone hysterectomy, bilateral salpingectomy or bilateral oophorectomy and have no medical proven ovarian failure), their female partners must take effective contraceptive measures (such as oral/injection/vaginal or implantable hormone contraceptives, or other physical barrier, surgery and other female contraceptive methods) within 30 days after the last administration;
• Those who are infertile, such as those who have undergone effective sterilization operations, take additional effective contraceptive measures when they are not sure whether they have sperm);
• Male subjects agree to avoid donating sperm within 30 days from the initiation of drug administration until the last administration.
• 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 ≥ 18 years old;
• In the first 2 days (48 hours) before randomization, COVID-19 nucleic acid detected by RT-PCR is positive;

You may not qualify if:

• According to the judgment of the principal investigator, the participant is accompanied with suspected COVID-19 related clinical symptoms/signs;
• During screening, those who are judged to be clinically significant by the principal investigator through medical history inquiry, physical examination, vital signs, blood oxygen saturation (SpO2), laboratory examination, 12-lead electrocardiogram (ECG), abdominal ultrasound, chest X-ray examination, etc;
• Participants with clinically significant diseases (such as neuropsychiatric system, cardiovascular system, urinary system, digestive system, respiratory system, skeletal muscle system, endocrine and metabolic system, blood system, skin disease, immune system, tumor, etc.) are evaluated by the researcher as not suitable for this study;
• Previous major surgery, or according to the judgment of the principal investigator, there is any physiological or disease or condition that may affect the absorption of the study drug (such as gastrectomy, cholecystectomy, enterotomy, etc.);
• According to the judgment of the principal investigator, there is any physical or psychological disease or condition that may increase the risk of the test, affect the compliance of the subject with the other case, or affect the subject's completion of the test;
• Within 2 weeks or 5 half-life (whichever is longer) before screening, and during the whole study period, it is expected to take any medicine and health care products, including prescription drugs, over-the-counter drugs and Chinese herbal medicine (including oral contraceptives, external spermicide, drugs with systemic therapeutic effects through percutaneous absorption and St. John's wort);
• Participants have participated in any clinical study or taken study drugs within 3 months before screening;
• Have a history of vaccination within 30 days before screening, or plan to have a vaccination throughout the study period;
• Difficult in blood sample collection, unable to tolerate multiple venous blood collection and any contraindication of blood sample collection;
• Large amount of blood loss or donation (more than 250mL) within 3 months before screening;
• At screening, 12-lead ECG is abnormal and had clinical significance according to the judgment of the researcher, such as the QT interval (QTcB) corrected by Bazett (formula QT/RR0.5), the absolute value of QTcB in males is more than 450ms, and the absolute value of QTcB in females is more than 470ms;
• When screening, endogenous creatinine clearance rate is less than 80mL/min, according to Cockcroft-Gault formula: endogenous creatinine clearance rate (mL/min)=(140 - age) × body weight (kg) 72 × serum creatinine concentration (mg/dL) (female × 0.85);
• During the screening period and/or the baseline period, the blood pressure and pulse are within the following range: systolic blood pressure \<90 mmHg or ≥ 140 mmHg, diastolic blood pressure \<60 mmHg or ≥ 90 mmHg, pulse \<55 bpm or \>100 bpm;
• Have a history of drug dependence or drug abuse in the past, or have a positive urine drug test during screening;
• Those who have a history of severe allergy to drugs, food and articles (including allergy to latex, dust mites, pollen, etc.), or are known to be allergic to the test drug ingredients;

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

The First Affiliated Hospital of Shandong First Medical University Shandong Provincial Qianfoshan Hospital

Jinan, Shandong, China

RECRUITING

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Linlin Song

CONTACT

0531-89268311; 13335126599@189.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2023
• First Posted: March 22, 2023
• Study Start: February 1, 2023
• Primary Completion: May 31, 2023
• Study Completion: June 30, 2023
• Last Updated: April 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)