A Phase III Study to Evaluate the Efficacy and Safety of ZM-H1505R in Patients With CHB

NCT07095855 | Not Yet Recruiting Phase 3

• 1 other identifier: ZM-H1505R-301
• Study Type: interventional
• Target: 1,300
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Hepatitis B

Keywords

ZM-H1505R; Hepatitis B; CHB

Outcome Measures

Primary Outcomes (1)

• 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)

  48 week

Secondary Outcomes (10)

• 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.

  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

  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

  Part A(double-blind treatment period):from baseline to week 48

• Percentage of subjects with quantitative HBV DNA ≤ 20 IU/mL

  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

  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.

Study Arms (2)

Group A:ZM-H1505R + NAs

EXPERIMENTAL

ZM-H1505R 100mg,QD + NAs(ETV or TDF or TAF or TMF)

Drug: ZM-H1505R 100mg; Combination Product: NAs （"Entecavir"or"Tenofovir"or"Tenofovir alafenamide"or"TMF"） treatments

Group B: ZM-H1505R Placebo + NAs

PLACEBO COMPARATOR

ZM-H1505R Placebo 100mg,QD + NAs(ETV or TDF or TAF or TMF)

Other: ZM-H1505R Placebo; Combination Product: NAs （"Entecavir"or"Tenofovir"or"Tenofovir alafenamide"or"TMF"） treatments

Interventions

ZM-H1505R 100mg DRUG

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.

Group A:ZM-H1505R + NAs

ZM-H1505R Placebo OTHER

ZM-H1505R Placebo(100mg,QD) will be used in Part A double-blind treatment period for 48 weeks.

Group B: ZM-H1505R Placebo + NAs

NAs （"Entecavir"or"Tenofovir"or"Tenofovir alafenamide"or"TMF"） treatments COMBINATION_PRODUCT

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.

Group A:ZM-H1505R + NAs; Group B: ZM-H1505R Placebo + NAs

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and sign the written informed consent form;
• Adult males and females aged 18-65 years(inclusive) at screening;
• Have been used NAs monotherapy with ETV(0.5 mg or 1.0mg, QD),TDF (300 mg, QD),TAF (25 mg, QD),or TMF (25 mg, OD)for at least 12 months at the time of enrollment; Have been on stable and continuous use of one of these medications for at least 6months, and do not plan to switch to any other NAs class of medications after entering this clinical trial;
• Evidence of prior HBV infection (e.g., HBsAg and/or HBV DNA positive), or HBsAg positive at screening;
• HBV DNA ≥50 IU/mL as measured by a local healthcare facility within 30 days prior to screening and HBV DNA ≥50 IU/mL as confirmed by central laboratory testing at the time of screening;
• HBeAg positivity confirmed by central laboratory testing at screening;
• 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.

You may not qualify if:

• 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, or liver stiffness test (FibroTouch) ≥ 9.6 kPa(FibroScan preferred) ;
• 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;
• Subjects meeting any of the following clinical laboratory parameters at screening:
• Hemoglobin \< 110 g/L (for males) or \< 100 g/L (for females);
• Platelet count \< 90 × 109/L;
• Neutrophil count \< 1.5 × 109/L;
• Alanine aminotransferase (ALT) or Aspartate aminotransferase(AST)\> 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).
• 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;
• 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.
• 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.
• 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;

Sponsors & Collaborators

• Shanghai Zhimeng Biopharma, Inc.: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, 130000, China

Location

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Project Manager

CONTACT

+8615800984667; adeng@corebiopharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• 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 14, 2025
• First Posted: July 31, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)