A Study to Evaluate the Efficacy and Safety of ZM-H1505R in Combination With ETV Compared With ETV Monotherapy in Patients With CHB
- Conditions
- Hepatitis B, Chronic
- Interventions
- Registration Number
- NCT05484466
- Lead Sponsor
- Shanghai Zhimeng Biopharma, Inc.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A:ZM-H1505R 50 mg QD + Baraclude 0.5 mg QD ZM-H1505R 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 . Group A:ZM-H1505R 50 mg QD + Baraclude 0.5 mg QD ZM-H1505R placebo 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 . Group C:ZM-H1505R placebo QD + Baraclude 0.5 mg QD Baraclude 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 . Group B:ZM-H1505R 100 mg QD + Baraclude 0.5 mg QD Baraclude 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 . Group A:ZM-H1505R 50 mg QD + Baraclude 0.5 mg QD Baraclude 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 . Group C:ZM-H1505R placebo QD + Baraclude 0.5 mg QD ZM-H1505R placebo 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 . Group B:ZM-H1505R 100 mg QD + Baraclude 0.5 mg QD ZM-H1505R 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 .
- Primary Outcome Measures
Name Time Method Percentage of subjects who achieves complete virologic response (CVR) at week 24 of treatment period. 24 weeks 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. 24 weeks 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
Name Time Method 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. 60 weeks 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 60 weeks 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 60 weeks 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 Baseline, Week 24, Week 48 and Week 60 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.
Changes from baseline in quantitative hepatitis B core-related antigen (HBcrAg) at weeks 4, 12, 24, 36, 48, and 60 Baseline；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 60THBV genotypic resistance. 60 weeks The number of cases and percentages of subjects with HBV genotypic resistance.
Plasma concentration of ZM-H1505R Baseline；at weeks 4, 12, 24, 36, 48 For determination of ZM-H1505R plasma concentration, sparse PK blood samples will be collected in all subjects.
Percentage of subjects whose quantitative HBV RNA is ≤ 10 copies/mL at each scheduled visits 60 weeks 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 visitsChanges from baseline in quantitative hepatitis B surface antigen (HBsAg) at weeks 4, 12, 24, 36, 48, and 60 Baseline;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 60Percentage of subjects achieving HBsAg loss at weeks 24, 48, and 60 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 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 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 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.)
Trial Locations
- Locations (1)
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China