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A Study to Evaluate the Efficacy and Safety of ZM-H1505R in Combination With ETV Compared With ETV Monotherapy in Patients With CHB

Primary Purpose

Hepatitis B, Chronic

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
ZM-H1505R
ZM-H1505R placebo
Baraclude
Sponsored by
Shanghai Zhimeng Biopharma, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic focused on measuring Hepatitis B, Chronic, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase IIa

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria

  • 1.Able to understand and sign the written informed consent form (the informed consent should be obtained prior to any study procedure);
  • 2.Males and females aged 18-65 (inclusive);
  • 3.Have been using ETV (0.5 mg, QD) monotherapy for at least 12 months at the time of screening;
  • 4.Able to provide evidence of exsisting HBV infection (e.g., HBsAg and/or HBV DNA positive), or HBsAg positive at screening
  • 5.HBV DNA < 2000 IU/mL but ≥ 50 IU/mL in 2 consecutive tests at least 30 days apart during the screening period (serum samples will be delivered to the designated central laboratory for testing);
  • 6.Women of childbearing potential must have negative serum pregnancy tests at screening and baseline;
  • 7.Women of childbearing potential or males with female partners of childbearing potential must agree to voluntarily use the contraceptive methods specified in the protocol from screening to 28 days after the last dose of the study (see Appendix 1).

Exclusion criteria

  • 1.Progressive fibrosis or cirrhosis detected at screening, or progressive fibrosis or cirrhosis defined as follows: Metavir ≥ 3 or Ishak fibrosis score ≥ 4 by liver biopsy within 1 year prior to screening; or in the absence of an appropriate liver biopsy, liver stiffness test (FibroScan)

    ≥ 9 kPa within 3 months prior to screening;

  • 2.History of hepatocellular carcinoma (HCC); or serum alpha-fetoprotein (AFP) ≥ 50 ng/mL at screening, or imaging examination such as abdominal ultrasound, CT (computed tomography) or MRI (magnetic resonance imaging) suggesting possible HCC;
  • 3.Subjects meeting any of the following clinical laboratory parameters at screening:

    1. Hemoglobin < 120 g/L (for males) or < 110 g/L (for females);
    2. Platelet count < 100 × 109/L;
    3. Neutrophil count < 1.5 × 109/L;
    4. Alanine aminotransferase (ALT) > 3 × upper limit of normal (×ULN);
    5. International normalized ratio (INR) of prothrombin time > 1.3;
    6. Albumin < 35 g/L;
    7. Total bilirubin > 2 × ULN, and direct bilirubin > 1.5 × ULN;
    8. Estimated glomerular filtration rate < 60 mL/min/1.73 m2 (calculated using the CKD-MDRD formula, see Appendix 2).
  • 4.Abnormal and clinically significant electrocardiogram (ECG) at screening, e.g. QTcF interval (QT corrected using the Fridericia formula): > 450 ms for males, > 470 ms for females;
  • 5.Co-infection with human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV) or hepatitis E virus (HEV); Note: Subjects with positive HCV antibody (Ab) but negative HCV RNA and subjects with positive HEV immunoglobulin M (IgM) but negative HEV RNA will NOT be excluded.
  • 6.Other malignancy unless the subject's malignancy has been cured by surgical resection (e.g., basal cell skin cancer); Note: Subjects who are suspected of having malignancy must be excluded regardless of evidence of local recurrence or metastasis.
  • 7.History of chronic liver disease with a non-HBV etiology, such as alcoholic liver disease, autoimmune liver disease, hereditary liver disease, non-alcoholic fatty liver disease, except for simple fatty liver disease;
  • 8.Other concurrent severe systemic diseases or clinical manifestations, for which the investigator considers not suitable to participate in this study, including but not limited to:

    1. Circulatory system diseases: such as unstable angina, myocardial infarction, congestive heart failure, and poorly controlled or refractory hypertension (for example, after medication treatment, systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg);
    2. Respiratory system diseases: such as severe chronic obstructive pulmonary disease;
    3. Primary or secondary renal diseases (such as chronic renal decompensation and renal diseases associated with diabetes, hypertension, and vascular diseases);
    4. Endocrine system diseases: such as poorly controlled diabetes or thyroid disease;
    5. Autoimmune diseases: such as systemic lupus erythematosus, idiopathic thrombocytopenic purpura, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, autoimmune hemolytic anemia, and psoriasis;
    6. Neuropsychiatric diseases: such as epilepsy, schizophrenia, and depression;
  • 9.Use of any investigational product or drug not approved by regulatory authorities within 3 months prior to screening;
  • 10.History of persistent alcohol comsumption (alcohol consumption exceeding 40 g ethanol for males or 20 g ethanol for females per day on average) within 6 months prior to screening;
  • 11.History of drug dependence or drug abuse;
  • 12.Pregnant or breastfeeding women;
  • 13.Known hypersensitivity to the active ingredient or formulation excipients of the investigational drug;
  • 14.Inappropriate for the study participation for any reason not otherwise listed as judged by the investigator.

Sites / Locations

  • The First Hospital of Jilin UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Group A:ZM-H1505R 50 mg QD + Baraclude 0.5 mg QD

Group B:ZM-H1505R 100 mg QD + Baraclude 0.5 mg QD

Group C:ZM-H1505R placebo QD + Baraclude 0.5 mg QD

Arm Description

The treatment regimen is as follow: Group A: ZM-H1505R 50 mg QD + Baraclude 0.5 mg QD 48weeks After 48 weeks of treatment with the corresponding regimen, subjects will continue to take Baraclude 0.5 mg QD, as a monotherapy for a 12-week .

The treatment regimen is as follow: Group B: ZM-H1505R 100 mg QD + Baraclude 0.5 mg QD 48weeks After 48 weeks of treatment with the corresponding regimen, subjects will continue to take Baraclude 0.5 mg QD, as a monotherapy for a 12-week .

The treatment regimen is as follow: Group C: ZM-H1505R placebo QD + Baraclude 0.5 mg QD 48weeks After 48 weeks of treatment with the corresponding regimen, subjects will continue to take Baraclude 0.5 mg QD, as a monotherapy for a 12-week .

Outcomes

Primary Outcome Measures

Percentage of subjects who achieves complete virologic response (CVR) at week 24 of treatment period.
To evaluate the efficacy of ZM-H1505R in combination with ETV (Baraclude®) versus Baraclude® monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Percentage of subjects who achieves complete virologic response (CVR) at week 24 of treatment period. (CVR is defined as HBV DNA ≤ 10 IU/mL.)
To evaluate the safety of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months.
An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE was any unfavorable and unintended sign, symptom, disease, and/or laboratory or physiological observation that may or may not be related to the investigational medicinal product.

Secondary Outcome Measures

To evaluate the long-term safety of ZM-H1505R in combination with Baraclude® versus Baraclude® monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months.
An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE was any unfavorable and unintended sign, symptom, disease, and/or laboratory or physiological observation that may or may not be related to the investigational medicinal product.
Percentage of subjects who achieves CVR at each scheduled visits other than week 24 visit
To evaluate the long-term safety of ZM-H1505R in combination with Baraclude versus Baraclude® monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Percentage of subjects who achieves CVR at each scheduled visits other than week 24 visit. (CVR is defined as HBV DNA ≤ 10 IU/mL.)
Time to achieve CVR in each group
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Time to achieve CVR in each group (CVR is defined as HBV DNA ≤ 10 IU/mL.)
Changes from baseline in quantitative HBV ribonucleic acid (RNA) at each scheduled visits
Change in Mean log10 HBV RNA From Baseline (Day -60 to Day -1) to Week 24, Week 48, or Week 60 on ZM-H1505R + SOC ETV as Compared to Placebo + SOC ETV Hepatitis B virus (HBV) RNA was measured using COBAS 6800. The lower limit of quantitation (LLOQ) was 10 Copies/mL.
Percentage of subjects whose quantitative HBV RNA is ≤ 10 copies/mL at each scheduled visits
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Percentage of subjects whose quantitative HBV RNA is ≤ 10 copies/mL at each scheduled visits
Changes from baseline in quantitative hepatitis B surface antigen (HBsAg) at weeks 4, 12, 24, 36, 48, and 60
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Changes from baseline in quantitative hepatitis B surface antigen (HBsAg) at weeks 4, 12, 24, 36, 48, and 60
Percentage of subjects achieving HBsAg loss at weeks 24, 48, and 60
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. 6) Percentage of subjects achieving HBsAg loss at weeks 24, 48, and 60; (HBsAg loss is defined as HBsAg positive before treatment and HBsAg negative after treatment.)
Percentage of subjects achieving HBsAg seroconversion at weeks 24, 48, and 60
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Percentage of subjects achieving HBsAg seroconversion at weeks 24, 48, and 60; (HBsAg seroconversion is defined as HBsAg positive before treatment and HBsAg negative after treatment, with hepatitis B surface antibody [HBsAb] changed to positive.)
Percentage of subjects achieving hepatitis B e antigen (HBeAg) loss at weeks 24, 48, and 60
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Percentage of subjects achieving hepatitis B e antigen (HBeAg) loss at weeks 24, 48, and 60 (only for subjects who are HBeAg positive at baseline); (HBeAg loss is defined as a subject who is HBeAg positive before treatment and becomes HBeAg negative after treatment.)
Percentage of subjects with HBeAg seroconversion at weeks 24, 48, and 60
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Percentage of subjects with HBeAg seroconversion at weeks 24, 48, and 60 (only for subjects who are HBeAg positive at baseline); (HBeAg seroconversion is defined as HBeAg positive before treatment and HBeAg negative after treatment, with hepatitis B e antibody [HBeAb] changed to positive.)
Changes from baseline in quantitative hepatitis B core-related antigen (HBcrAg) at weeks 4, 12, 24, 36, 48, and 60
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Changes from baseline in quantitative hepatitis B core-related antigen (HBcrAg) at weeks 4, 12, 24, 36, 48, and 60
THBV genotypic resistance.
The number of cases and percentages of subjects with HBV genotypic resistance.
Plasma concentration of ZM-H1505R
For determination of ZM-H1505R plasma concentration, sparse PK blood samples will be collected in all subjects.

Full Information

First Posted
July 20, 2022
Last Updated
May 4, 2023
Sponsor
Shanghai Zhimeng Biopharma, Inc.
Collaborators
Tigermed Consulting Co., Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05484466
Brief Title
A Study to Evaluate the Efficacy and Safety of ZM-H1505R in Combination With ETV Compared With ETV Monotherapy in Patients With CHB
Official Title
A Phase IIa Study to Evaluate the Efficacy and Safety of ZM-H1505R in Combination With Entecavir (ETV) Compared With ETV Monotherapy in Patients With Chronic Hepatitis B Who Have Received ETV Monotherapy for at Least 12 Months
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 11, 2022 (Actual)
Primary Completion Date
December 20, 2022 (Actual)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Zhimeng Biopharma, Inc.
Collaborators
Tigermed Consulting Co., Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a multicenter, randomized, double-blind, placebo-controlled phase IIa study, designed to evaluate the efficacy and safety of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects with HBV DNA <2000 IU/mL but ≥ 50 IU/mL and who have received ETV (0.5 mg, once daily [QD)] monotherapy for at least 12 months. The study is planned to enroll 90 adult CHB subjects who have received ETV monotherapy for at least 12 months and are still receiving ETV monotherapy (0.5 mg, QD) continuously. Eligible subjects will be randomized in a 1:1:1 ratio into 3 treatment groups. Both HBeAg positive and negative subjects will be included. There will be 20 HBeAg positive subjects and 10 HBeAg negative subjects in each treatment group. After 48 weeks of treatment with the corresponding regimen, subjects will continue to take Baraclude 0.5 mg QD, as a monotherapy for a 12-week follow-up period for observation of efficacy and safety of ZM-H1505R.
Detailed Description
This is a multicenter, randomized, double-blind, placebo-controlled phase IIa study, designed to evaluate the efficacy and safety of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects with HBV DNA <2000 IU/mL but ≥ 50 IU/mL and who have received ETV (0.5 mg, once daily [QD)] monotherapy for at least 12 months. The study is planned to enroll 90 adult CHB subjects who have received ETV monotherapy for at least 12 months and are still receiving ETV monotherapy (0.5 mg, QD) continuously. Eligible subjects will be randomized in a 1:1:1 ratio into 3 treatment groups. Both HBeAg positive and negative subjects will be included. There will be 20 HBeAg positive subjects and 10 HBeAg negative subjects in each treatment group. The treatment regimens in each group are as follows: Group A: ZM-H1505R 50 mg QD + Baraclude 0.5 mg QD Group B: ZM-H1505R 100 mg QD + Baraclude 0.5 mg QD Group C: ZM-H1505R placebo QD + Baraclude 0.5 mg QD After 48 weeks of treatment with the corresponding regimen, subjects will continue to take Baraclude 0.5 mg QD, as a monotherapy for a 12-week follow-up period for observation of efficacy and safety of ZM-H1505R.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic
Keywords
Hepatitis B, Chronic, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase IIa

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
The study is planned to enroll 90 adult CHB subjects who have received ETV monotherapy for at least 12 months and are still receiving ETV monotherapy (0.5 mg, QD) continuously. Eligible subjects will be randomized in a 1:1:1 ratio into 3 treatment groups. Both HBeAg positive and negative subjects will be included. There will be 20 HBeAg positive subjects and 10 HBeAg negative subjects in each treatment group. The treatment regimens in each group are as follows: Group A: ZM-H1505R 50 mg QD + Baraclude 0.5 mg QD Group B: ZM-H1505R 100 mg QD + Baraclude 0.5 mg QD Group C: ZM-H1505R placebo QD + Baraclude 0.5 mg QD After 48 weeks of treatment with the corresponding regimen, subjects will continue to take Baraclude 0.5 mg QD, as a monotherapy for a 12-week follow-up period for observation of efficacy and safety of ZM-H1505R.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group A:ZM-H1505R 50 mg QD + Baraclude 0.5 mg QD
Arm Type
Experimental
Arm Description
The treatment regimen is as follow: Group A: ZM-H1505R 50 mg QD + Baraclude 0.5 mg QD 48weeks After 48 weeks of treatment with the corresponding regimen, subjects will continue to take Baraclude 0.5 mg QD, as a monotherapy for a 12-week .
Arm Title
Group B:ZM-H1505R 100 mg QD + Baraclude 0.5 mg QD
Arm Type
Experimental
Arm Description
The treatment regimen is as follow: Group B: ZM-H1505R 100 mg QD + Baraclude 0.5 mg QD 48weeks After 48 weeks of treatment with the corresponding regimen, subjects will continue to take Baraclude 0.5 mg QD, as a monotherapy for a 12-week .
Arm Title
Group C:ZM-H1505R placebo QD + Baraclude 0.5 mg QD
Arm Type
Placebo Comparator
Arm Description
The treatment regimen is as follow: Group C: ZM-H1505R placebo QD + Baraclude 0.5 mg QD 48weeks After 48 weeks of treatment with the corresponding regimen, subjects will continue to take Baraclude 0.5 mg QD, as a monotherapy for a 12-week .
Intervention Type
Drug
Intervention Name(s)
ZM-H1505R
Intervention Description
There are three groups in this study. ZM-H1505R will be used in group A and Group B ,Subjects can use it for 48 weeks Group A: 30 subjects; ZM-H1505R 50 mg QD +ZM-H1505R placebo; Group B: 30 subjects; ZM-H1505R 100 mg QD
Intervention Type
Other
Intervention Name(s)
ZM-H1505R placebo
Intervention Description
There are three groups in this study. ZM-H1505R will be used in group A and Group C ,Subjects can use it for 48 weeks Group A: 30 subjects;ZM-H1505R 50 mg +ZM-H1505R placebo 50mg QD ; Group C: 30 subjects;ZM-H1505R placebo 100mg QD
Intervention Type
Combination Product
Intervention Name(s)
Baraclude
Intervention Description
All subjects were orally administered once a day at night : Baraclude® 0.5 mg QD,60weeks
Primary Outcome Measure Information:
Title
Percentage of subjects who achieves complete virologic response (CVR) at week 24 of treatment period.
Description
To evaluate the efficacy of ZM-H1505R in combination with ETV (Baraclude®) versus Baraclude® monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Percentage of subjects who achieves complete virologic response (CVR) at week 24 of treatment period. (CVR is defined as HBV DNA ≤ 10 IU/mL.)
Time Frame
24 weeks
Title
To evaluate the safety of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months.
Description
An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE was any unfavorable and unintended sign, symptom, disease, and/or laboratory or physiological observation that may or may not be related to the investigational medicinal product.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
To evaluate the long-term safety of ZM-H1505R in combination with Baraclude® versus Baraclude® monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months.
Description
An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE was any unfavorable and unintended sign, symptom, disease, and/or laboratory or physiological observation that may or may not be related to the investigational medicinal product.
Time Frame
60 weeks
Title
Percentage of subjects who achieves CVR at each scheduled visits other than week 24 visit
Description
To evaluate the long-term safety of ZM-H1505R in combination with Baraclude versus Baraclude® monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Percentage of subjects who achieves CVR at each scheduled visits other than week 24 visit. (CVR is defined as HBV DNA ≤ 10 IU/mL.)
Time Frame
60 weeks
Title
Time to achieve CVR in each group
Description
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Time to achieve CVR in each group (CVR is defined as HBV DNA ≤ 10 IU/mL.)
Time Frame
60 weeks
Title
Changes from baseline in quantitative HBV ribonucleic acid (RNA) at each scheduled visits
Description
Change in Mean log10 HBV RNA From Baseline (Day -60 to Day -1) to Week 24, Week 48, or Week 60 on ZM-H1505R + SOC ETV as Compared to Placebo + SOC ETV Hepatitis B virus (HBV) RNA was measured using COBAS 6800. The lower limit of quantitation (LLOQ) was 10 Copies/mL.
Time Frame
Baseline, Week 24, Week 48 and Week 60
Title
Percentage of subjects whose quantitative HBV RNA is ≤ 10 copies/mL at each scheduled visits
Description
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Percentage of subjects whose quantitative HBV RNA is ≤ 10 copies/mL at each scheduled visits
Time Frame
60 weeks
Title
Changes from baseline in quantitative hepatitis B surface antigen (HBsAg) at weeks 4, 12, 24, 36, 48, and 60
Description
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Changes from baseline in quantitative hepatitis B surface antigen (HBsAg) at weeks 4, 12, 24, 36, 48, and 60
Time Frame
Baseline;at weeks 4, 12, 24, 36, 48, and 60
Title
Percentage of subjects achieving HBsAg loss at weeks 24, 48, and 60
Description
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. 6) Percentage of subjects achieving HBsAg loss at weeks 24, 48, and 60; (HBsAg loss is defined as HBsAg positive before treatment and HBsAg negative after treatment.)
Time Frame
At weeks 24, 48, and 60
Title
Percentage of subjects achieving HBsAg seroconversion at weeks 24, 48, and 60
Description
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Percentage of subjects achieving HBsAg seroconversion at weeks 24, 48, and 60; (HBsAg seroconversion is defined as HBsAg positive before treatment and HBsAg negative after treatment, with hepatitis B surface antibody [HBsAb] changed to positive.)
Time Frame
At weeks 24, 48, and 60
Title
Percentage of subjects achieving hepatitis B e antigen (HBeAg) loss at weeks 24, 48, and 60
Description
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Percentage of subjects achieving hepatitis B e antigen (HBeAg) loss at weeks 24, 48, and 60 (only for subjects who are HBeAg positive at baseline); (HBeAg loss is defined as a subject who is HBeAg positive before treatment and becomes HBeAg negative after treatment.)
Time Frame
At weeks 24, 48, and 60
Title
Percentage of subjects with HBeAg seroconversion at weeks 24, 48, and 60
Description
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Percentage of subjects with HBeAg seroconversion at weeks 24, 48, and 60 (only for subjects who are HBeAg positive at baseline); (HBeAg seroconversion is defined as HBeAg positive before treatment and HBeAg negative after treatment, with hepatitis B e antibody [HBeAb] changed to positive.)
Time Frame
At weeks 24, 48, and 60
Title
Changes from baseline in quantitative hepatitis B core-related antigen (HBcrAg) at weeks 4, 12, 24, 36, 48, and 60
Description
To evaluate other virology indicators of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects who have received ETV monotherapy for at least 12 months. Changes from baseline in quantitative hepatitis B core-related antigen (HBcrAg) at weeks 4, 12, 24, 36, 48, and 60
Time Frame
Baseline;at weeks 4, 12, 24, 36, 48, and 60
Title
THBV genotypic resistance.
Description
The number of cases and percentages of subjects with HBV genotypic resistance.
Time Frame
60 weeks
Title
Plasma concentration of ZM-H1505R
Description
For determination of ZM-H1505R plasma concentration, sparse PK blood samples will be collected in all subjects.
Time Frame
Baseline;at weeks 4, 12, 24, 36, 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria 1.Able to understand and sign the written informed consent form (the informed consent should be obtained prior to any study procedure); 2.Males and females aged 18-65 (inclusive); 3.Have been used ETV (0.5 mg, QD) monotherapy for at least 12 months at the time of screening; and able to provide evidence of existing HBV infection (e.g., HBsAg and/or HBV DNA positive), or HBsAg positive at screening; 4.Plasma HBV DNA < 2000 IU/mL but ≥ 50 IU/mL in 2 consecutive tests at least 30 days apart during the screening period (serum samples will be delivered to the designated central laboratory for testing) 5.Women of childbearing potential or males with female partners of childbearing potential must agree to voluntarily use the contraceptive methods specified in the protocol from screening to 28 days after the last dose of the study (see Appendix 1). Exclusion criteria 1.Progressive fibrosis or cirrhosis detected at screening, or progressive fibrosis or cirrhosis defined as follows: Metavir ≥ 3 or Ishak fibrosis score ≥ 4 by liver biopsy within 1 year prior to screening; or in the absence of an appropriate liver biopsy, liver stiffness test (FibroScan) ≥ 9 kPa within 3 months prior to screening; 2.History of hepatocellular carcinoma (HCC); or serum alpha-fetoprotein (AFP) ≥ 50 ng/mL at screening, or imaging examination such as abdominal ultrasound, CT (computed tomography) or MRI (magnetic resonance imaging) suggesting possible HCC; 3.Subjects meeting any of the following clinical laboratory parameters at screening: Hemoglobin < 120 g/L (for males) or < 110 g/L (for females); Platelet count < 100 × 109/L; Neutrophil count < 1.5 × 109/L; Alanine aminotransferase (ALT) > 3 × upper limit of normal (×ULN); International normalized ratio (INR) of prothrombin time > 1.3; Albumin < 35 g/L; Total bilirubin > 2 × ULN, and direct bilirubin > 1.5 × ULN; Estimated glomerular filtration rate < 60 mL/min/1.73 m2 (calculated using the CKD-MDRD formula, see Appendix 2). 4.Abnormal result of electrocardiogram (ECG) at screening and inappropriate for the study participation judged by the investigator; Or QTcF (QT corrected using the Fridericia formula): > 450 ms for males, > 470 ms for females at screening; 5.Co-infection with human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV) or hepatitis E virus (HEV); Note: Subjects with positive HCV antibody (Ab) but negative HCV RNA and subjects with positive HEV immunoglobulin M (IgM) but negative HEV RNA will NOT be excluded. 6.Other malignancy unless the subject's malignancy has been cured by surgical resection (e.g., basal cell skin cancer); Note: Subjects who are suspected of having malignancy must be excluded regardless of evidence of local recurrence or metastasis. 7.History of chronic liver disease with a non-HBV etiology, such as alcoholic liver disease, autoimmune liver disease, hereditary liver disease, non-alcoholic fatty liver disease, except for simple fatty liver disease; 8.Other concurrent severe systemic diseases or clinical manifestations, for which the investigator considers not suitable to participate in this study, including but not limited to: Circulatory system diseases: such as unstable angina, myocardial infarction, congestive heart failure, and poorly controlled or refractory hypertension (for example, after medication treatment, systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg); Respiratory system diseases: such as severe chronic obstructive pulmonary disease; Primary or secondary renal diseases (such as chronic renal decompensation and renal diseases associated with diabetes, hypertension, and vascular diseases); Endocrine system diseases: such as poorly controlled diabetes or thyroid disease; Autoimmune diseases: such as systemic lupus erythematosus, idiopathic thrombocytopenic purpura, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, autoimmune hemolytic anemia, and psoriasis; Neuropsychiatric diseases: such as epilepsy, schizophrenia, and depression; 9.Use of any investigational product or drug not approved by regulatory authorities within 3 months prior to screening; 10.History of persistent alcohol comsumption (alcohol consumption exceeding 40 g ethanol for males or 20 g ethanol for females per day on average) within 6 months prior to screening; 11.History of drug dependence or drug abuse; 12.Pregnant or breastfeeding women; 13.Known hypersensitivity to the active ingredient or formulation excipients of the investigational drug; 14.Inappropriate for the study participation for any reason not otherwise listed as judged by the investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Project Manager
Phone
15800984667
Email
adeng@corebiopharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Junqi Niu
Organizational Affiliation
The First Hospital of Jilin University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Hospital of Jilin University
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Junqi Niu
Phone
13756661205
Email
junqiniu@aliyun.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study to Evaluate the Efficacy and Safety of ZM-H1505R in Combination With ETV Compared With ETV Monotherapy in Patients With CHB

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