Chronic HBV Infection
Conditions
Keywords
HBeAg-positive or negative
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.
Interventions
DRUGHS-10234
Drug: HS-10234 HS-10234 25mg will administer orally once daily Drug: TDF placebo TDF placebo 300mg will administer orally once daily
DRUGTDF
Drug: TDF TDF 300mg will administer orally once daily Drug: HS-10234 placebo HS-10234 placebo 25mg will administer orally once daily
Sponsors
Jiangsu Hansoh Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must meet all of the following inclusion criteria to be eligible for participation in this study: 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
* Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation the percentage of Participants with Hepatitis B Virus (HBV) DNA < 20 IU/mL | Week 48 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation the percent Change from Baseline in Hip BMD | Week 48 | Percent Change from Baseline in Hip Bone Mineral Density (BMD) at Week 48 |
| Evaluation the percent Change from Baseline in Spine BMD | Week 48 | Percent Change from Baseline in Spine BMD at Week 48 |
| Evaluation the change from Baseline in Serum Creatinine | Week 48 | Change from Baseline in Serum Creatinine at Week 48 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Evaluation the proportion of Patients Achieving Hepatitis B Surface Antigen (HBsAg) Loss | Week 48, 96 and 144 | Proportion of Patients Achieving Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144 |
| Evaluation the proportion of Patients Achieving HBsAg Seroconversion | Week 48, 96 and 144 | Proportion of Patients Achieving HBsAg Seroconversion at Weeks 48, 96, 144 |
| Evaluation the proportion of patients achieving HBeAg loss | Week 48, 96 and 144 | Proportion of patients achieving HBeAg loss at weeks 48, 96, 144 |
| Evaluation the proportion of patients achieving HBeAg seroconversion | Week 48, 96 and 144 | Proportion of patients achieving HBeAg seroconversion at weeks 48, 96, 144 |
Countries
China
Outcome results
None listed