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

NCT03903796 | Completed Phase 3

• 1 other identifier: HS-10234-301
• Study Type: interventional
• Target: 963
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic HBV Infection

Keywords

HBeAg-positive or negative

Outcome Measures

Primary Outcomes (1)

• Evaluation the percentage of Participants with Hepatitis B Virus (HBV) DNA < 20 IU/mL

  The primary efficacy endpoint was the proportion of patients with HBV DNA \< 20 IU/mL at week 48 in all patients who are randomly assigned and received HS-10234 25 mg or TDF 300 mg. The safety and tolerance were also observed in two treatment groups.

  Week 48

Secondary Outcomes (3)

• Evaluation the percent Change from Baseline in Hip BMD

  Week 48

• Evaluation the percent Change from Baseline in Spine BMD

  Week 48

• Evaluation the change from Baseline in Serum Creatinine

  Week 48

Other Outcomes (4)

• Evaluation the proportion of Patients Achieving Hepatitis B Surface Antigen (HBsAg) Loss

  Week 48, 96 and 144

• Evaluation the proportion of Patients Achieving HBsAg Seroconversion

  Week 48, 96 and 144

• Evaluation the proportion of patients achieving HBeAg loss

  Week 48, 96 and 144

Study Arms (3)

HS-10234 25mg

EXPERIMENTAL

HS-10234 + TDF placebo for up to 96 weeks

Drug: HS-10234; Drug: TDF

TDF 300mg

ACTIVE COMPARATOR

TDF + HS-10234 placebo for up to 96 weeks

Drug: HS-10234; Drug: TDF

Open-label HS-10234

EXPERIMENTAL

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.

Drug: HS-10234

Interventions

HS-10234 DRUG

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

HS-10234 25mg; Open-label HS-10234; TDF 300mg

TDF DRUG

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

HS-10234 25mg; TDF 300mg

Eligibility Criteria

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

You may qualify if:

• Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study screening.
• 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.
• Documented evidence of chronic HBV infection (e.g. HBsAg positive for more than 6 months).
• 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.
• 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.
• Any previous treatment with interferon (pegylated or non-pegylated) must have ended at least 6 months prior to the baseline visit.
• 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).
• \) Must be willing and able to comply with all study requirements.

You may not qualify if:

• Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study.
• Males and females of reproductive potential who are unwilling to use an "effective", protocol specified method(s) of contraception during the study.
• Co-infection with HCV virus, HIV, or HDV.
• Evidence of hepatocellular carcinoma (e.g. as evidenced by recent imaging).
• Any history of, or current evidence of, clinical hepatic decompensation (e.g. ascites encephalopathy or variceal hemorrhage).
• 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)
• Received solid organ or bone marrow transplant.
• Significant renal, cardiovascular, pulmonary, or neurological disease in the opinion of the investigator.

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, China

Location

Related Publications (4)

• 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.

  PMID: 39528324 DERIVED

• 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.

  PMID: 39528323 DERIVED

• 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.

  PMID: 36969889 DERIVED

• 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.

  PMID: 34587302 DERIVED

Study Officials

• Guo Xiaolin, MD

  The First Hospital of Jilin University, Jilin Province

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2019
• First Posted: April 4, 2019
• Study Start: August 16, 2018
• Primary Completion: May 31, 2020
• Study Completion: June 7, 2024
• Last Updated: December 17, 2024

Record last verified: 2024-12

Locations

CN (1)