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

NCT05470829 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ZM-H1505R-102
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers; Hepatitis B, Chronic

Keywords

Hepatitis B, Chronic; randomized; double-blind; placebo-controlled; phase Ib

Outcome Measures

Primary Outcomes (4)

• To evaluate the safety and tolerability of ZM-H1505R among Chinese healthy subjects

  12 healthy subjects with Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatmen

  42 days

• Pharmacokinetics indicators

  PK parameters of plasma ZM-H1505R in 12 healthy subjects

  42 days

• Pharmacodynamics indicators

  PK parameters of plasma ZM-H1505R in 30 chronic hepatitis B virus-infected patients

  56 days

• To evaluate the safety and tolerability of ZM-H1505R among chronic hepatitis B virus-infected patients

  30 chronic hepatitis B virus-infected patients with Abnormal Laboratory Values and/or Adverse Events That Are

  56 Days

Study Arms (4)

Part 1 75mg ZM-H1505R or placebo

EXPERIMENTAL

75 mg was selected for PK bridging.Twelve healthy subjects were enrolled,of which 8 subjects received ZM-H1505R and 4 subjects received placebo. Subjects were administrated in the morning under fasting conditions on Day 1 and afterwards Day 4 - Day 14 once daily,i.e. after 3-day washout period and followed by 11-day consecutive administration.Safety and tolerability evaluation was performed on Day 3,Day 6,Day 10 and Day 17 after the initial administration. Two sentinel subjects (one male and one female) were enrolled to reveived ZM-H1505R.When safety evaluation on Day 3 showed that ZM-H1505R could be tolerated by sentinel subjects,and study drug concentration of sentinel subjects after the initial administration had been analysed so that PK sampling timepoints for the remaining subjects was determined, the remaining 10 subjects were enrolled to receive ZM-H1505R or placebo at a 3:2 ratio in a randomized manner.

Drug: ZM-H1505R; Other: ZM-H1505R Placebo

Cohort 1 of Part 2 50mg ZM-H1505R or placebo

EXPERIMENTAL

Subjects were enrolled in sequence from 50 mg dose group (cohort 1). Dose ascending was continued when safety evaluation on Day 8 showed that the lower dose could be tolerated. Ten chronic hepatitis B virus-infected patients were enrolled in each cohort to receive ZM-H1505R (n=8) or placebo (n=2). Subjects in all cohorts were administrated on Day 1 - Day 28 once daily (consecutive 28-day administration) in the morning under fasting conditions. Two sentinel subjects were enrolled in each cohort to reveived ZM-H1505R. When safety evaluation on Day 3 showed that ZM-H1505R could be tolerated by sentinel subjects, the remaining 8 subjects including HBeAg-positive and HBeAg-negative patients at a ratio of 4:4 were enrolled to receive ZM-H1505R or placebo at a 3:1 ratio in a randomized manner.

Drug: ZM-H1505R; Other: ZM-H1505R Placebo

Cohort 2 of Part 2 100mg ZM-H1505R or placebo

EXPERIMENTAL

Subjects were enrolled in sequence from 100 mg dose group (cohort 2). Dose ascending was continued when safety evaluation on Day 8 showed that the lower dose could be tolerated. Ten chronic hepatitis B virus-infected patients were enrolled in each cohort to receive ZM-H1505R (n=8) or placebo (n=2). Subjects in all cohorts were administrated on Day 1 - Day 28 once daily (consecutive 28-day administration) in the morning under fasting conditions. Two sentinel subjects were enrolled in each cohort to reveived ZM-H1505R. When safety evaluation on Day 3 showed that ZM-H1505R could be tolerated by sentinel subjects, the remaining 8 subjects including HBeAg-positive and HBeAg-negative patients at a ratio of 4:4 were enrolled to receive ZM-H1505R or placebo at a 3:1 ratio in a randomized manner.

Drug: ZM-H1505R; Other: ZM-H1505R Placebo

Cohort 3 of Part 2 200mg ZM-H1505R or placebo

EXPERIMENTAL

Subjects were enrolled in sequence from 200 mg dose group (cohort 3). Ten chronic hepatitis B virus-infected patients were enrolled in each cohort to receive ZM-H1505R (n=8) or placebo (n=2). Subjects in all cohorts were administrated on Day 1 - Day 28 once daily (consecutive 28-day administration) in the morning under fasting conditions. Two sentinel subjects were enrolled in each cohort to reveived ZM-H1505R. When safety evaluation on Day 3 showed that ZM-H1505R could be tolerated by sentinel subjects, the remaining 8 subjects including HBeAg-positive and HBeAg-negative patients at a ratio of 4:4 were enrolled to receive ZM-H1505R or placebo at a 3:1 ratio in a randomized manner.

Drug: ZM-H1505R; Other: ZM-H1505R Placebo

Interventions

ZM-H1505R DRUG

Part 1 dosage form:75mg dosage:Tablet frequency: Quaque die duration: Day1; Day 4\~ Day 14 Cohort 1 of Part 2 dosage form:50mg dosage:Tablet frequency: Quaque die duration: Day 1\~ Day 28 Cohort 2 of Part 2 dosage form:100mg dosage:Tablet frequency: Quaque die duration: Day 1\~ Day 28 Cohort 3 of Part 2 dosage form:200mg dosage:Tablet frequency: Quaque die duration: Day 1\~ Day 28

Cohort 1 of Part 2 50mg ZM-H1505R or placebo; Cohort 2 of Part 2 100mg ZM-H1505R or placebo; Cohort 3 of Part 2 200mg ZM-H1505R or placebo; Part 1 75mg ZM-H1505R or placebo

ZM-H1505R Placebo OTHER

Part 1 dosage form:75mg dosage:Tablet frequency: Quaque die duration: Day1; Day 4\~ Day 14 Cohort 1 of Part 2 dosage form:50mg dosage:Tablet frequency: Quaque die duration: Day 1\~ Day 28 Cohort 2 of Part 2 dosage form:100mg dosage:Tablet frequency: Quaque die duration: Day 1\~ Day 28 Cohort 3 of Part 2 dosage form:200mg dosage:Tablet frequency: Quaque die duration: Day 1\~ Day 28

Cohort 1 of Part 2 50mg ZM-H1505R or placebo; Cohort 2 of Part 2 100mg ZM-H1505R or placebo; Cohort 3 of Part 2 200mg ZM-H1505R or placebo; Part 1 75mg ZM-H1505R or placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Shanghai Zhimeng Biopharma, Inc.: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, China

Location

Related Publications (1)

• Jia H, Mai J, Wu M, Chen H, Li X, Li C, Liu J, Liu C, Hu Y, Zhu X, Jiang X, Hua B, Xia T, Liu G, Deng A, Liang B, Guo R, Lu H, Wang Z, Chen H, Zhang Z, Zhang H, Niu J, Ding Y. Safety, tolerability, pharmacokinetics, and antiviral activity of the novel core protein allosteric modulator ZM-H1505R (Canocapavir) in chronic hepatitis B patients: a randomized multiple-dose escalation trial. BMC Med. 2023 Mar 16;21(1):98. doi: 10.1186/s12916-023-02814-w.

  PMID: 36927420 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Junqi Niu

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

• Yanhua Ding

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

• Hongxin Piao

  Yanbian University Affiliated Hospital (Yanbian Hospital)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2022
• First Posted: July 22, 2022
• Study Start: May 27, 2021
• Primary Completion: November 17, 2021
• Study Completion: November 17, 2021
• Last Updated: July 22, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)