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
Overview
- Phase
- Phase 2
- Intervention
- ZM-H1505R
- Conditions
- Hepatitis B, Chronic
- Sponsor
- Shanghai Zhimeng Biopharma, Inc.
- Enrollment
- 90
- Locations
- 1
- Primary Endpoint
- Percentage of subjects who achieves complete virologic response (CVR) at week 24 of treatment period.
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Group A:ZM-H1505R 50 mg QD + Baraclude 0.5 mg QD
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 .
Intervention: ZM-H1505R
Group A:ZM-H1505R 50 mg QD + Baraclude 0.5 mg QD
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 .
Intervention: ZM-H1505R placebo
Group A:ZM-H1505R 50 mg QD + Baraclude 0.5 mg QD
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 .
Intervention: Baraclude
Group B:ZM-H1505R 100 mg QD + Baraclude 0.5 mg QD
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 .
Intervention: ZM-H1505R
Group B:ZM-H1505R 100 mg QD + Baraclude 0.5 mg QD
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 .
Intervention: Baraclude
Group C:ZM-H1505R placebo QD + Baraclude 0.5 mg QD
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: ZM-H1505R placebo
Group C:ZM-H1505R placebo QD + Baraclude 0.5 mg QD
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: Baraclude
Outcomes
Primary Outcomes
Percentage of subjects who achieves complete virologic response (CVR) at week 24 of treatment period.
Time Frame: 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.
Time Frame: 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 Outcomes
- 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)
- Percentage of subjects who achieves CVR at each scheduled visits other than week 24 visit(60 weeks)
- Time to achieve CVR in each group(60 weeks)
- Changes from baseline in quantitative HBV ribonucleic acid (RNA) at each scheduled visits(Baseline, Week 24, Week 48 and Week 60)
- 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)
- THBV genotypic resistance.(60 weeks)
- Plasma concentration of ZM-H1505R(Baseline；at weeks 4, 12, 24, 36, 48)
- Percentage of subjects whose quantitative HBV RNA is ≤ 10 copies/mL at each scheduled visits(60 weeks)
- Changes 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)
- Percentage of subjects achieving HBsAg loss at weeks 24, 48, and 60(At weeks 24, 48, and 60)
- Percentage of subjects achieving HBsAg seroconversion at weeks 24, 48, and 60(At weeks 24, 48, and 60)
- Percentage of subjects achieving hepatitis B e antigen (HBeAg) loss at weeks 24, 48, and 60(At weeks 24, 48, and 60)
- Percentage of subjects with HBeAg seroconversion at weeks 24, 48, and 60(At weeks 24, 48, and 60)