Study of the Efficacy and Safety of HS-10234 in Patients With Chronic Hepatitis B Virus Infection

NCT ID: NCT03903796

Last Updated: 2024-12-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 963 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-16
• Study Completion Date: 2024-06-07

Brief Summary

The primary objective of this study is to compare the safety and efficacy of HS-10234 versus tenofovir disoproxil fumarate (TDF) in treatment-naive and treatment-experienced adults with chronic hepatitis B virus (HBV) infection.

Detailed Description

This is a phase 3, randomized, multicenter, double-blind, double-dummy, parallel-controlled, non-inferiority trial to evaluate the safety and efficacy of HS-10234 25 mg qd versus TDF 300 mg qd. Patients with chronic HBV infection who are positive or negative for the hepatitis B e antigen (HBeAg) will be randomly assigned (2:1) to receive either 25 mg HS-10234 or 300 mg TDF with matching placebo. Randomization will be done by a computer-generated allocation sequence stratified by plasma HBV DNA concentration (HBV DNA< 8 log10IU/mL；HBV DNA ≥8 log10IU/mL) and previous treatment experience (treatment-naive and treatment-experienced). All patients will receive 144 weeks of antiviral therapy. After 96 weeks of double-blind treatment, all subjects will be eligible to receive open-label HS-10234 until 144 weeks.

The primary efficacy endpoint is the proportion of patients with HBV DNA less than 20 IU/mL at week 48 in all patients who are randomly assigned and received at least one dose of study drug using a missing-equals-failed approach. Key pre-specified safety endpoints are bone and renal parameters at week 48. Other pre-specified endpoints include viral suppression, serologic response, normalization of alanine aminotransferase (ALT) levels and the emergence of resistance mutations at week 48, 96 and 144.

Conditions

Chronic HBV Infection

Keywords

HBeAg-positive or negative

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

HS-10234 25mg

HS-10234 + TDF placebo for up to 96 weeks

Group Type: EXPERIMENTAL

HS-10234

Intervention Type: DRUG

Drug: HS-10234 HS-10234 25mg will administer orally once daily Drug: TDF placebo TDF placebo 300mg will administer orally once daily

TDF

Intervention Type: DRUG

Drug: TDF TDF 300mg will administer orally once daily Drug: HS-10234 placebo HS-10234 placebo 25mg will administer orally once daily

TDF 300mg

TDF + HS-10234 placebo for up to 96 weeks

Group Type: ACTIVE_COMPARATOR

HS-10234

Intervention Type: DRUG

Drug: HS-10234 HS-10234 25mg will administer orally once daily Drug: TDF placebo TDF placebo 300mg will administer orally once daily

TDF

Intervention Type: DRUG

Drug: TDF TDF 300mg will administer orally once daily Drug: HS-10234 placebo HS-10234 placebo 25mg will administer orally once daily

Open-label HS-10234

All participants who complete the double-blind period (96 weeks) will be eligible to receive open-label HS-10234 until week 144 of the study.

Group Type: EXPERIMENTAL

HS-10234

Intervention Type: DRUG

Drug: HS-10234 HS-10234 25mg will administer orally once daily Drug: TDF placebo TDF placebo 300mg will administer orally once daily

Interventions

HS-10234

Drug: HS-10234 HS-10234 25mg will administer orally once daily Drug: TDF placebo TDF placebo 300mg will administer orally once daily

Intervention Type: DRUG

TDF

Drug: TDF TDF 300mg will administer orally once daily Drug: HS-10234 placebo HS-10234 placebo 25mg will administer orally once daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study screening.

2. Male and non-pregnant, non-lactating females, from 18 up to 65 years of age (based on the date of the screening visit). A negative serum pregnancy test at screening is required for female subjects of childbearing potential.

3. Documented evidence of chronic HBV infection (e.g. HBsAg positive for more than 6 months).

4. HBeAg-positive or HBeAg-negative chronic hepatitis B with all of the following: HBV DNA ≥ 2 x 104 IU/mL; Screening serum 1 ULN < ALT level ≤ 10 ULN.

5. Treatment-naive subjects (defined as < 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue) OR treatment-experienced subjects (defined as subjects meeting all entry criteria [including HBV DNA and serum ALT criteria] and with ≥ 12 weeks of previous treatment with any nucleoside or nucleotide analogue) will be eligible for enrollment. Treatment-experienced subjects receiving oral antiviral treatment at Screening must continue their treatment regimen until the time of randomization, when it will be discontinued.

6. Any previous treatment with interferon (pegylated or non-pegylated) must have ended at least 6 months prior to the baseline visit.

7. Estimated creatinine clearance (CLcr) ≥ 50 mL/min（using the Cockcroft-Gault method）based on serum creatinine and actual body weight as measured at the screening evaluation, as follows:

（140-age in years）(body weight [kg]) (72)(serum creatinine [mg/dL]） 8) Normal ECG (or if abnormal, determined by the Investigator not to be clinically significant).

9) Must be willing and able to comply with all study requirements.

Exclusion Criteria

1. Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study.

2. Males and females of reproductive potential who are unwilling to use an "effective", protocol specified method(s) of contraception during the study.

3. Co-infection with HCV virus, HIV, or HDV.

4. Evidence of hepatocellular carcinoma (e.g. as evidenced by recent imaging).

5. Any history of, or current evidence of, clinical hepatic decompensation (e.g. ascites encephalopathy or variceal hemorrhage).

6. Abnormal hematological and biochemical parameters, including:

• Hemoglobin < 10 g/dl
• Absolute neutrophil count < 0.75 × 109/L
• Platelets ≤ 50 × 109/L
• AST or ALT > 10 × ULN
• Total Bilirubin > 2.5 × ULN
• Albumin < 3.0 g/dL
• INR > 1.5 × ULN (unless stable on anticoagulant regimen)

7. Received solid organ or bone marrow transplant.

8. Significant renal, cardiovascular, pulmonary, or neurological disease in the opinion of the investigator.

9. Significant bone disease (e.g. osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochrondroses), or multiple bone fractures.

10. Malignancy within the 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc).

11. Currently receiving therapy with immunomodulators (e.g. corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion.

12. Known hypersensitivity to study drugs, metabolites, or formulation excipients.

13. Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance.

14. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements.

15. Subjects on prohibited concomitant medications. Subjects on prohibited medications, otherwise eligible, will need a wash out period of at least 30 days.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu Hansoh Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guo Xiaolin, MD

Role: PRINCIPAL_INVESTIGATOR

The First Hospital of Jilin University, Jilin Province

Locations

The First Hospital of Jilin University

Changchun, Jilin, China

Countries

China

References

Liu ZH, Jin QL, Zhang YX, Gong GZ, Wu GC, Yao LF, Wen XF, Gao ZL, Huang Y, Yang DK, Chen EQ, Mao Q, Lin SD, Shang J, Gong HY, Zhong LH, Yin HF, Wang FM, Hu P, Zhang XQ, Gao QJ, Xia P, Li C, Niu JQ, Hou JL; TMF Study Group. [Safety profile of tenofovir amibufenamide therapy extension or switching in patients with chronic hepatitis B: a phase Ⅲ multicenter, randomized controlled trial]. Zhonghua Gan Zang Bing Za Zhi. 2024 Oct 20;32(10):893-903. doi: 10.3760/cma.j.cn501113-20240807-00366. Chinese.

Reference Type: DERIVED

PMID: 39528324 (View on PubMed)

Liu ZH, Jin QL, Zhang YX, Gong GZ, Wu GC, Yao LF, Wen XF, Gao ZL, Huang Y, Yang DK, Chen EQ, Mao Q, Lin SD, Shang J, Gong HY, Zhong LH, Yin HF, Wang FM, Hu P, Zhang XQ, Gao QJ, Jin CN, Li C, Niu JQ, Hou JL; TMF Study Group. [Efficacy evaluation of extending or switching to tenofovir amibufenamide in patients with chronic hepatitis B: a phase Ⅲ randomized controlled study]. Zhonghua Gan Zang Bing Za Zhi. 2024 Oct 20;32(10):883-892. doi: 10.3760/cma.j.cn501113-20240807-00365. Chinese.

Reference Type: DERIVED

PMID: 39528323 (View on PubMed)

Liu Z, Jin Q, Zhang Y, Gong G, Wu G, Yao L, Wen X, Gao Z, Huang Y, Yang D, Chen E, Mao Q, Lin S, Shang J, Gong H, Zhong L, Yin H, Wang F, Hu P, Wu Q, Pan C, Jia W, Li C, Sun C, Niu J, Hou J; TMF Study Group. 96-Week Treatment of Tenofovir Amibufenamide and Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients. J Clin Transl Hepatol. 2023 Jun 28;11(3):649-660. doi: 10.14218/JCTH.2022.00058. Epub 2022 Nov 1.

Reference Type: DERIVED

PMID: 36969889 (View on PubMed)

Liu Z, Jin Q, Zhang Y, Gong G, Wu G, Yao L, Wen X, Gao Z, Huang Y, Yang D, Chen E, Mao Q, Lin S, Shang J, Gong H, Zhong L, Yin H, Wang F, Hu P, Xiao L, Li C, Wu Q, Sun C, Niu J, Hou J; TMF Study Group. Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B. Aliment Pharmacol Ther. 2021 Nov;54(9):1134-1149. doi: 10.1111/apt.16611. Epub 2021 Sep 29.

Reference Type: DERIVED

PMID: 34587302 (View on PubMed)

Other Identifiers

HS-10234-301

Identifier Type: -

Identifier Source: org_study_id