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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03903796
Recruitment Status : Recruiting
First Posted : April 4, 2019
Last Update Posted : April 4, 2019
Sponsor:
Information provided by (Responsible Party):
Jiangsu Hansoh Pharmaceutical Co., Ltd.

Tracking Information
First Submitted Date  ICMJE March 3, 2019
First Posted Date  ICMJE April 4, 2019
Last Update Posted Date April 4, 2019
Actual Study Start Date  ICMJE August 16, 2018
Estimated Primary Completion Date May 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 3, 2019)
Evaluation the percentage of Participants with Hepatitis B Virus (HBV) DNA < 20 IU/mL [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2019)
  • Evaluation the percent Change from Baseline in Hip BMD [ Time Frame: Week 48 ]
    Percent Change from Baseline in Hip Bone Mineral Density (BMD) at Week 48
  • Evaluation the percent Change from Baseline in Spine BMD [ Time Frame: Week 48 ]
    Percent Change from Baseline in Spine BMD at Week 48
  • Evaluation the change from Baseline in Serum Creatinine [ Time Frame: Week 48 ]
    Change from Baseline in Serum Creatinine at Week 48
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: April 3, 2019)
  • Evaluation the proportion of Patients Achieving Hepatitis B Surface Antigen (HBsAg) Loss [ Time Frame: 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 [ Time Frame: Week 48, 96 and 144 ]
    Proportion of Patients Achieving HBsAg Seroconversion at Weeks 48, 96, 144
  • Evaluation the proportion of patients achieving HBeAg loss [ Time Frame: Week 48, 96 and 144 ]
    Proportion of patients achieving HBeAg loss at weeks 48, 96, 144
  • Evaluation the proportion of patients achieving HBeAg seroconversion [ Time Frame: Week 48, 96 and 144 ]
    Proportion of patients achieving HBeAg seroconversion at weeks 48, 96, 144
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Study of the Efficacy and Safety of HS-10234 in Patients With Chronic Hepatitis B Virus Infection
Official Title  ICMJE A Phase 3, Randomized, Multicenter, Double-blind, Double-dummy, Parallel-controlled Study to Evaluate the Safety and Efficacy of HS-10234 25 mg QD Versus TDF 300 mg QD for the Treatment of Patients With HBeAg+/- Chronic HBV Infection.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Chronic HBV Infection
Intervention  ICMJE
  • Drug: HS-10234
    Drug: HS-10234 HS-10234 25mg will administer orally once daily Drug: TDF placebo TDF placebo 300mg will administer orally once daily
  • Drug: TDF
    Drug: TDF TDF 300mg will administer orally once daily Drug: HS-10234 placebo HS-10234 placebo 25mg will administer orally once daily
Study Arms  ICMJE
  • Experimental: HS-10234 25mg
    HS-10234 + TDF placebo for up to 96 weeks
    Interventions:
    • Drug: HS-10234
    • Drug: TDF
  • Active Comparator: TDF 300mg
    TDF + HS-10234 placebo for up to 96 weeks
    Interventions:
    • Drug: HS-10234
    • Drug: TDF
  • Experimental: 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.
    Intervention: Drug: HS-10234
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 3, 2019)
963
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 31, 2022
Estimated Primary Completion Date May 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 exclusion criteria are not to be enrolled in this study:

    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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Hou Jinlin, MD 0086-20-61641941 jlhousmu@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03903796
Other Study ID Numbers  ICMJE HS-10234-301
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jiangsu Hansoh Pharmaceutical Co., Ltd.
Study Sponsor  ICMJE Jiangsu Hansoh Pharmaceutical Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Guo Xiaolin, MD The First Hospital of Jilin University, Jilin Province
PRS Account Jiangsu Hansoh Pharmaceutical Co., Ltd.
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP