A Multiple-dose Study in Chinese Subjects to Evaluate Safety,Tolerability,PK and PD of ZM-H1505R

• Status: Completed
• Trial end date: 2021-11-17
• Target enrollment: 0
• Participant gender: All

Summary

This phase Ib study included two parts in which Part I was to evaluate the safety and bridge for PK among healthy Chinese subjects and Part II were about study among Chinese chronic hepatitis B virus-infected patients. Study of Part II was carried out following the safety assessment and racial difference evaluation in Part I.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Shanghai Zhimeng Biopharma, Inc.

Criteria

Inclusion Criteria:

• Able to sign Inform Consent Forms before study, and fully understand the study contents, process and potential adverse reactions;

• Able to complete the study in compliance with the protocol;

• Subjects (including their partners) agreed to adopt effective contraceptive measurements from screening to 6 months after the last administration.

Part I Proprietary:

• Male and female subjects between 18 and 50 years of age, inclusive;

• At least 50 kg for male subjects, 45 kg for female, with a Body Mass Index (BMI) between 18-28 ;

• Normal or abnormal but of no clinical significance results for physical examination and vital signs.

Part II Proprietary::

• Male and female subjects between 18 and 65 years of age, inclusive;

• At least 50 kg for male subjects, 45 kg for female subjects, with a Body Mass Index (BMI) between 18-35 kg/m2, inclusive, BMI = weight (kg) / height 2 (m2);

• Any proof of HBV infection more than 6 months (including outpatient/inpatient medical records, HBV DNA, HBsAg test sheets, etc.); or with IgM HBcAb negative and HBsAg positive at screening;

• No history of therapy including interferon/nucleoside or analog at screening, or discontinuation for more than 1 year from interferon therapy or more than 6 months from nucleoside analog therapy;

• HBV DNA ≥ 2×105 IU/mL for HBeAg-positive patients and HBV DNA ≥ 2×104 IU/mL for HBeAg-negative patients at screening;

• Serum ALT lower than 5×upper limit of normal at screening.

Exclusion Criteria:

• Major trauma or surgery within 3 months before screening;

• History of treatment that may interfere with drug absorption (e.g, subtotal gastrectomy);

• Blood donation or massive blood loss (> 450 mL) within 3 months prior to screening;

• Any history of allergy suspected to be due to any component of the study drug, or allergic constitution (allergy to multiple drug and food);

• A history of narcotic drugs intake or alcohol abuse ;

• Acute infection within 2 weeks before screening;

• Suffering from serious diseases of the circulatory, respiratory, urinary, vascular, endocrine, immune, mental and nervous systems;

• History of myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass grafting, heart failure of grade III or IV, or stroke within 6 months prior to screening;

• Patients with existing malignant tumors (except for skin non-melanoma, cervical intraepithelial neoplasia, thyroid tumor, breast tumor, etc. after treatment with no signs of recurrence);

• Any surgery or hospitalization anticipated during the study;

• Treatment history of immunosuppressants, immunomodulators (thymosin) and cytotoxic drugs within 6 months before study administration;

• Medication history of definitely strong CYP3A4 inhibitors or inducers within 2 weeks before screening;

• Involved in any other study drug administration or clinical study of medical devices within 1 month before screening; Involved in any clinical study of HBV virus nucleocapsid inhibitors in the past;

• Any abnormality of electrocardiogram not suitable for the study judged by physician;

• Positive pregnancy test results or subject is lactating for female subjects;

• Positive test results of HCV-Ab, HCV core antigen and HCV RNA (PCR); or HIV antibody; or Treponema pallidum antibody further confirmed by rapid plasma reagin (RPR) test;

• Consumption of chocolate or any diets containing caffeine or rich in xanthine, or any alcohol-containing products within 48 h before the initial administration;

• Positive results of drug abuse tests (morphine, marijuana) or alcohol breath tests;

• Other conditions in which subjects are not suitable for the study in the opinion of investigators.

Part I Proprietary:

• More than 5 cigarettes everyday within 1 month before the study;

• Intake of any prescription or over-the-counter (OTC) drugs, vitamin, herbs, other inappropriate diet or supplements in opinion of investigators within 7 days before screening;

• Positive HBsAg test results;

• Any clinically significant abnormalities in laboratory tests.

Part II Proprietary :

• Estimated glomerular filtration rate (eGFR) ˂ 60 mL/min/1.73 m2 based on serum creatinine and formula for modification of diet in renal disease (MDRD) based on values at screening;

• Patients with clinically significant acute or chronic liver disease not caused by HBV infection (including but not limited to alcoholic liver disease, severe or higher non-alcoholic fatty liver disease, autoimmune liver disease, Gilbert syndrome or other hereditary liver disease, drug-induced liver disease, etc. );

• Liver cirrhosis at clinical consideration or/and liver stiffness measurements (LSM) ≥ 12.4 kPa (for patients with ALT greater than the upper limit of normal, LSM ≥ 17.5 kPa); 27) Patients with clinically significant cardiac arrhythmias; history of risk factors for Torsade de Pointes (TdP) syndrome;

• Uncontrolled hypertension with systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg at screening;

• Patients with type I diabetes, or with newly diagnosed or poorly controlled type II diabetes (HbA1c > 8.5%);

• Left ventricular ejection fraction < 50%.