This study is divided into two parts. Part A is a multicenter, randomized, double-blind, placebo controlled phase Ill clinical trial, designed to evaluate the efficacy and safety of ZM-H1505R in combination with NAs versus NAs monotherapy with HBV DNA ≥ 50 IU/mL and are HBeAg positive who have received NAs monotherapy for at least 12months.Part B is an open-label extension and follow-up period designed to evaluate the long-term safety and efficacy of ZM-H1505R in combination with NAs.
This study is divided into two parts. Part A is a multicenter, randomized, double-blind, placebo controlled phase Ill clinical trial, designed to evaluate the efficacy and safety of ZM-H1505R in combination with NAs versus NAs monotherapy with HBV DNA ≥ 50 IU/mL and are HBeAg positive who have received NAs monotherapy for at least 12months.Part B is an open-label extension and follow-up period designed to evaluate the long-term safety and efficacy of ZM-H1505R in combination with NAs. \- Part A (Double-Blind Treatment Period): Eligible subjects will be randomized in a 1:1 ratio into 2 groups. Group A:ZM-H1505R 100mg +NAs Group B:ZM-H1505R placebo +NAs Two randomization stratification factors were set: NAs type of ETV, TDF,TAF, or TMF (no less than 15% of ETV, TDF, and TAF); HBV DNA \<2000 IU/mL and HBV DNA \>2000 IU/mL . All subjects completed a 48-week efficacy and safety evaluation followed by an interim analysis, the results of which were used to submit an NDA application. \- Part B (Open-Label Extension Period): At the end of the 48-week randomized double-blind treatment period, all eligible subjects will transfer to the open-label extension period and were treated with ZM-H1505R 100 mg +NAs while the study drug was evaluated for efficacy and safety until the end of the 144 weeks. \- Follow-up Period: At the end of the 144-week open-label extension period, all subjects will continue to take NAs, as a monotherapy for a 4-week follow-up period for observation of efficacy and safety of after discontinuation of study drug in ZM-H1505R .
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
ZM-H1505R(100mg,QD) will be used in Part A double-blind treatment period for 48 weeks and Part B open-label extension period 144 weeks.
ZM-H1505R Placebo(100mg,QD) will be used in Part A double-blind treatment period for 48 weeks.
All eligible subjects will be use NAs ("Entecavir"or"Tenofovir"or"Tenofovir alafenamide"or"TMF") treatments during the study for 148 weeks, including Part A and Part B. Subjects will continue to use the NAs as combination therapy before enrollment, the dosage will not be adjusted during the study. Subjects use in accordance with medical advice andinstructions.
The First Hospital of Jilin University
Changchun, Jilin, China
Percentage of subjects achieves complete virologic response (CVR) at week 48 of treatment.
To evaluate the efficacy of ZM-H1505R in combination with NAs versus NAs monotherapy in adult CHB subjects who have received NAs monotherapy for at least 12 months. (CVR is defined as HBV DNA ≤ 10 IU/mL)
Time frame: 48 week
Safety of ZM-H1505R in combination with NAs versus NAs monotherapy in adult CHB subjects who have received NAs monotherapy for at least 12 months.
Safety during the 48-week double-blind treatment period, the open-label extension period, and the follow-up period.
Time frame: From baseline to the end of follow-up period(Part A and Part B), assessed up to 148 weeks.
Percentage of subjects who achieve CVR at each scheduled visit other than week 48 visit
CVR is defined as HBV DNA ≤ 10 IU/mL).
Time frame: Part A(double-blind treatment period):from baseline to week 48; Part B (open-label extension period and follow-up period):from week 48 to week 148.
Time to achieve CVR in each group
CVR is defined as HBV DNA ≤ 10 IU/mL
Time frame: Part A(double-blind treatment period):from baseline to week 48
Percentage of subjects with quantitative HBV DNA ≤ 20 IU/mL
Time frame: Part A(double-blind treatment period):from baseline to week 48; Part B (open-label extension period and follow-up period):from week 48 to week 148.
Changes from baseline in quantitative HBV RNA
Time frame: Part A(double-blind treatment period):from baseline to week 48; Part B (open-label extension period and follow-up period):from week 48 to week 148.
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Enrollment
1,300
Percentage of subjects who achieve LLOQ of quantitative HBV RNA
Time frame: Part A(double-blind treatment period):from baseline to week 48; Part B (open-label extension period and follow-up period):from week 48 to week 148.
Changes from baseline in quantitative serum HBsAg
Time frame: Part A(double-blind treatment period):from baseline to week 48; Part B (open-label extension period and follow-up period):from week 48 to week 148.
Changes from baseline in HBeAg at each scheduled visit
Time frame: Part A(double-blind treatment period):from baseline to week 48; Part B (open-label extension period and follow-up period):from week 48 to week 148.
Changes from baseline in quantitative serum HBcrAg at each scheduled visit;
Time frame: Part A(double-blind treatment period):from baseline to week 48; Part B (open-label extension period and follow-up period):from week 48 to week 148.
Changes from baseline in liver stiffness test (FibroScan/FibroTouch)
Time frame: Part A(double-blind treatment period):at week24 and week 48; Part B (open-label extension period and follow-up period):from week 48 to week 148.