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

NCT05484466 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: ZM-H1505R-201
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis B, Chronic

Keywords

Hepatitis B, Chronic; Multicenter; Randomized; Double-Blind; Placebo-Controlled; Phase IIa

Outcome Measures

Primary Outcomes (2)

• 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.)

  24 weeks

• 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.

  24 weeks

Secondary Outcomes (13)

• 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

• Percentage of subjects whose quantitative HBV RNA is ≤ 10 copies/mL at each scheduled visits

  60 weeks

Study Arms (3)

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

EXPERIMENTAL

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 .

Drug: ZM-H1505R; Other: ZM-H1505R placebo; Combination Product: Baraclude

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

EXPERIMENTAL

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 .

Drug: ZM-H1505R; Combination Product: Baraclude

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

PLACEBO COMPARATOR

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 .

Other: ZM-H1505R placebo; Combination Product: Baraclude

Interventions

ZM-H1505R DRUG

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

Group A:ZM-H1505R 50 mg QD + Baraclude 0.5 mg QD; Group B:ZM-H1505R 100 mg QD + Baraclude 0.5 mg QD

ZM-H1505R placebo OTHER

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

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

Baraclude COMBINATION_PRODUCT

All subjects were orally administered once a day at night ： Baraclude® 0.5 mg QD，60weeks

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

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 (the informed consent should be obtained prior to any study procedure);
• Males and females aged 18-65 (inclusive);
• 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;
• 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)
• 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).

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;
• 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 \< 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).
• 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.

Sponsors & Collaborators

• Shanghai Zhimeng Biopharma, Inc.: lead
• Tigermed Consulting Co., Ltd: collaborator

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, 130000, China

RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir

Condition Hierarchy (Ancestors)

Hepatitis B; 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

Study Officials

• Junqi Niu

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Project Manager

CONTACT

15800984667; adeng@corebiopharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 20, 2022
• First Posted: August 2, 2022
• Study Start: November 11, 2022
• Primary Completion: December 20, 2022
• Study Completion: December 30, 2024
• Last Updated: May 8, 2023

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)