<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03798119</url>
  </required_header>
  <id_info>
    <org_study_id>KMUHIRB-F(II)-20180111</org_study_id>
    <nct_id>NCT03798119</nct_id>
  </id_info>
  <brief_title>TAF Switch in F3/4 CHB pt With Partial Response to NUC (ESTAB-AFPVR)</brief_title>
  <official_title>Efficacy and Safety of Switching to Tenofovir Alafenamide for Chronic Hepatitis B Patients With Advanced Fibrosis and Partial Virologic Responses to Oral Nucleos(t)Ide Analogues</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kaohsiung Medical University Chung-Ho Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kaohsiung Medical University Chung-Ho Memorial Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A total of 80 adult chronic hepatitis B patients with advanced liver fibrosis (including&#xD;
      fibrosis stage 3 and cirrhosis), who are currently on nucleot(s)ide analogs (except tenofovir&#xD;
      alafenamide) therapy with detectable HBV DNA after 52 weeks of therapy will switch prior NUCs&#xD;
      to TAF 25 mg/day for 96 weeks&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Overview&#xD;
&#xD;
      Dosage regimen: Patients of CHB with advanced fibrosis and partial virological response to&#xD;
      NUCs will be considered eligible for the present study. The enrollment will be up to the&#xD;
      physician's discretion. The drug will be administered 1 pill (25 mg) per day orally, per&#xD;
      manufacturers' instructions, and can be taken with food.&#xD;
&#xD;
      Compliance: Enrolled patients must be monitored according to the protocol, GCP, and clinical&#xD;
      practice guidelines.&#xD;
&#xD;
      Study population: Approximately 80 adult CHB patients with advanced fibrosis (including&#xD;
      fibrosis stage 3 and cirrhosis), who are currently on NUCs (except TAF) therapy with&#xD;
      detectable HBV DNA after 52 weeks of therapy will switch prior NUCs to TAF 25 mg/day for 96&#xD;
      weeks. For patients of fibrosis stage 3, the numbers of enrolled patients will be no more&#xD;
      than 40% of total enrolled patients.&#xD;
&#xD;
      Study Objectives&#xD;
&#xD;
      Primary objective:&#xD;
&#xD;
      • To describe the improvement of rate of viral suppression with TAF in patients of partial&#xD;
      virological response with previous anti-HBV NUCs.&#xD;
&#xD;
      Secondary objective&#xD;
&#xD;
        -  To describe the persistence or improvement of rate of ALT normalization (local and AASLD&#xD;
           criteria) with TAF in patients of partial virological response with previous anti-HBV&#xD;
           NUCs.&#xD;
&#xD;
        -  To describe the trends in serum creatinine, calculated creatinine clearance, and renal&#xD;
           tubular function with TAF.&#xD;
&#xD;
        -  To describe the trends in bone mineral density with TAF.&#xD;
&#xD;
        -  To describe the progression/regression of liver fibrosis with TAF.&#xD;
&#xD;
        -  To describe the prespecified factors associated with viral suppression and/or ALT&#xD;
           normalization after switching to TAF, including viral resistance profiles, HBsAg levels&#xD;
           and HBV viral loads at the initiation of prior NUC and at the time of TAF switching, HBV&#xD;
           genotype, hepatic fibrosis, age, sex, prior preparations of NUCs, and host&#xD;
           immunogenetics.&#xD;
&#xD;
      Study Procedures:&#xD;
&#xD;
      Pre-Screening: Patients who are currently under HBV NUC, except TAF therapy, with liver&#xD;
      fibrosis stage 3 or 4 at the initiation of NUC, and with detectable HBV DNA after week 52 of&#xD;
      therapy will be considered eligible in this prospective interventional cohort study. If the&#xD;
      patient is deemed eligible to participate, the site will evaluate the potential patient using&#xD;
      the inclusion/exclusion criteria and fill out the CRF for the screening visit. The local&#xD;
      coordinator will transmit the pre-screening data to the central coordinator prior to the&#xD;
      actual screening/baseline visit. If the patient is deemed eligible by the Primary&#xD;
      Investigator, the patient will be given a study ID and allowed to enter the study.&#xD;
&#xD;
      Screening/Baseline: Written and informed consent will be obtained prior to any study&#xD;
      protocol-related procedures or data abstraction. If the patient has been pre-screened&#xD;
      approved and all lab data are available, the participant will begin the study TAF treatment&#xD;
      on the screening/baseline visit. The screening/baseline visit consists of obtaining written&#xD;
      and informed consent, reviewing the inclusion/exclusion criteria, confirming medical history,&#xD;
      completing a physical examination with vital signs and body weight, reviewing any concomitant&#xD;
      medications and study drug dispensing. HCV, HDV, and HIV antibody test will be performed&#xD;
      after written informed consent is obtained. The samples of HDV antibody test will be&#xD;
      collected at local site and sent to KMUH, tested by central lab. Baseline resistance testing&#xD;
      will also be performed by direct sequencing.&#xD;
&#xD;
      Procedures: laboratory tests including CBC (complete blood count) panel, Serum Bilirubin&#xD;
      (total/direct), AST, ALT, GGT, Albumin, BUN, Creatinine, Na, K, Phosphate, Prothrombin time&#xD;
      (INR), and Urine routine/creatinine/phosphate will be done every visit. Pregnant test (only&#xD;
      for women of child-bearing potential), Child-Pugh score, and FIB-4 score should also be done&#xD;
      every visit. AFP (alpha-fetoprotein), and Abdominal ultrasound should also be done every 3 to&#xD;
      6 months for HCC surveillance. HBV serological markers including HBeAg/HBeAb, HBV DNA&#xD;
      quantification (by central lab.) will be done every visit and HBsAg quantification (by&#xD;
      central lab.) every 6 months. Bone Density Scan (DEXA) will be done at week 24, 48, and 96.&#xD;
      Fibroscan/CAP will be performed at week 48, and 96 to determine regression of fibrosis. Blood&#xD;
      will be drawn at the site at which the participant was recruited, and processed by a lab&#xD;
      technician in the clinical laboratory at that respective site, except HDV antibody test and&#xD;
      HBsAg/HBV DNA quantification which will be performed by the central lab. at KMUH.&#xD;
&#xD;
      Treatment Visits: Treatment will consist of TAF 25 mg daily with food for 96 weeks. Treatment&#xD;
      visits will occur at week 4, 12, 24, 36, 48, 72, and 96 as per routine clinical care, except&#xD;
      for those who developed virological breakthrough, SAE, or others judged by the investigators.&#xD;
      At every visit, the patient must bring all study drugs (including empty bottles), so that the&#xD;
      study coordinator can count compliance using the number of remaining pills.&#xD;
&#xD;
      This schedule of clinic visits and laboratory tests are routine and standard practice for&#xD;
      investigators in their treatment of similar patients with CHB. Patients will be encouraged to&#xD;
      adhere to these recommendations. Results of these laboratory tests and clinical evaluations&#xD;
      will be recorded as well as any additional evaluations that are done as part of the patient's&#xD;
      clinical care that is pertinent to the objective of the study.&#xD;
&#xD;
      Discontinuation criteria: The study can be terminated at any time for any reasons by Primary&#xD;
      Investigator. Though there is no formal treatment stopping rules in this study, patients&#xD;
      might be asked to stop if there are any adverse events that the investigator feels make it&#xD;
      the patient's best interest to stop treatment.&#xD;
&#xD;
      Withdrawal of Subjects&#xD;
&#xD;
      Withdrawal Criteria:&#xD;
&#xD;
        -  Failure to follow study instructions or protocol violation that in the judgment of the&#xD;
           investigator&#xD;
&#xD;
        -  Serious Adverse Events that in the judgment of the investigator&#xD;
&#xD;
        -  Development of virological breakthrough (defined as reappearance of HBV DNA or at least&#xD;
           one log10 elevation of HBV DNA from nadir in 2 consecutive measurements one month apart.&#xD;
           further treatment plans are at the discretion of the treating physician and patient.&#xD;
&#xD;
        -  Any medical, psychosocial or administrative or other reasons that in the judgment of the&#xD;
           investigator, be detrimental to the patient's well-being.&#xD;
&#xD;
        -  Death&#xD;
&#xD;
        -  Withdrawal of informed consent&#xD;
&#xD;
      Adverse Events and Toxicity Management&#xD;
&#xD;
      Assessment of safety: Safety assessments will include monitoring of laboratory results, vital&#xD;
      signs, treatment-emergent adverse events, serious adverse events, etc. Safety assessments&#xD;
      will be performed at every clinic visit as part of clinical care and during follow-up visits.&#xD;
&#xD;
      If, in Primary Investigator's judgment, a clinical significant worsening from baseline is&#xD;
      observed in any laboratory or other test parameters, physical exam finding, or vital sign, a&#xD;
      corresponding clinical adverse event should be recorded.&#xD;
&#xD;
      If a specific medical diagnosis has been made, that diagnosis or syndrome should be recorded&#xD;
      as the adverse event, whenever possible. However, a complete description of the signs,&#xD;
      symptoms, and investigations which led to the diagnosis should be provided. For example, if&#xD;
      clinically significant elevations of liver function tests are known to be secondary to&#xD;
      hepatitis, &quot;hepatitis&quot; and not &quot;elevated liver function tests&quot; should be recorded. If the&#xD;
      cause is not known, the abnormal test or finding should be recorded as an adverse event,&#xD;
      using appropriate medical terminology (e/g/ thrombocytopenia, peripheral edema).&#xD;
&#xD;
      Maintenance of Safety Information: Safety information will be maintained in a clinical&#xD;
      database/repository in a retrievable format. At a minimum, at the end of the treatment phase&#xD;
      (=&quot;last patient off treatment&quot;) as well as the end of the follow-up phase (=&quot;last patient&#xD;
      out&quot;) of the study, Primary Investigator shall provide all adverse events, both serious and&#xD;
      non-serious, in report format.&#xD;
&#xD;
      Statistics&#xD;
&#xD;
      Data management and analysis will be performed at Kaohsiung Medical University Hospital.&#xD;
&#xD;
      Sample size to be used in the analysis: We calculated that a sample size of 80 patients with&#xD;
      a 10% dropout rate would provide 85% power to show increased to 30% of virologic response&#xD;
      (HBV DNA &lt;LLOQ) rate after 52 weeks of TAF therapy, compared to 15% of continuing prior NUC&#xD;
      therapy with a type I error rate of 0.05 for the one-tailed analyses of the primary endpoint.&#xD;
&#xD;
      Statistical methods to be employed: Descriptive and comparative statistics will be performed&#xD;
      for all demographic and clinical variables that are outcome endpoints for this pilot study.&#xD;
&#xD;
      Level of significance: A 95% confidence interval will be used.&#xD;
&#xD;
      Termination of trial: Termination of the trial will be upon completion of follow-up of all 80&#xD;
      subjects enrolled and/or up to the discretion of the primary investigator.&#xD;
&#xD;
      Procedure for missing, unused, spurious data: Data that is missing, unused or spurious data&#xD;
      will all be treated as missing data. This data will be marked as an empty field.&#xD;
&#xD;
      Deviation from the original statistical plan: Any deviation from the original statistical&#xD;
      plan will be up to the discretion of the primary investigator.&#xD;
&#xD;
      Selection of subjects to be included in analyses: All eligible subjects that have not been&#xD;
      withdrawn from the study will be included in analyses.&#xD;
&#xD;
      Interim analysis An interim analysis will be performed at Week 24 after all the 80 patients&#xD;
      enrolled.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 25, 2019</start_date>
  <completion_date type="Anticipated">August 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of virological response</measure>
    <time_frame>at 48 weeks of TAF therapy.</time_frame>
    <description>HBV DNA &lt;LLOQ</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of virological response</measure>
    <time_frame>at 96 weeks of treatment</time_frame>
    <description>HBV DNA &lt;LLOQ</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of ALT normalization</measure>
    <time_frame>at week 48 and 96</time_frame>
    <description>by local (&lt;40 U/L), and AASLD (male ≤35, female ≤25 U/L) criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of serum creatinine</measure>
    <time_frame>at week 48 and 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of calculated creatinine clearance (Cockcroft-Gault)</measure>
    <time_frame>at week 48 and 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in bone mineral density</measure>
    <time_frame>at week 48 and 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in liver fibrosis</measure>
    <time_frame>at week 48 and 96</time_frame>
    <description>determined by Fibroscan</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Hepatitis B</condition>
  <condition>Fibrosis and Cirrhosis of Liver</condition>
  <arm_group>
    <arm_group_label>Switch to TAF</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects who meet the inclusion and exclusion criteria will switch prior NUCs to TAF 25 mg/day for 96 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir Alafenamide</intervention_name>
    <description>Subjects in this group will switch prior nucleot(s)ide analogs to Tenofovir Alafenamide 25 mg/day for 96 weeks</description>
    <arm_group_label>Switch to TAF</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, age ≥20 years&#xD;
&#xD;
          2. CHB diagnosis confirmed by positive HBsAg or HBV DNA for more than 6 months, or&#xD;
             documented history of CHB in medical record before initiation of NUC therapy.&#xD;
&#xD;
          3. Currently maintained on nucleot(s)ide analogues (except TAF) therapy for more than one&#xD;
             year, with detectable HBV DNA after 52 weeks of therapy, detectable HBV DNA within 3-6&#xD;
             months prior to screening, and remains detectable HBV DNA at screening.&#xD;
&#xD;
          4. Patients with liver fibrosis stage 3 (defined as Metavir fibrosis stage 3 by liver&#xD;
             biopsy, or fibrosis-4 score 3.25 ~ 6.49, or ARFI 1.80 ~ 1.99 m/s, or Fibroscan&#xD;
             9.5~12.4 kPa), or cirrhosis (defined as Metavir fibrosis stage 4 by liver biopsy, or&#xD;
             APRI &gt;2, or fibrosis-4 score ≥ 6.5, or ARFI ≥ 2.0 m/s, or Fibroscan ≥12.5 kPa, or&#xD;
             image diagnosis with splenomegaly or esophageal/gastric varices) at the initiation of&#xD;
             prior NUC therapy or during the prior NUC therapy. The liver biopsy should be within 5&#xD;
             years, or during the prior NUC therapy and other non-invasive assessments should be&#xD;
             within 6 months at the initiation of NUC therapy or during the prior NUC therapy.&#xD;
&#xD;
          5. Estimated creatinine clearance &gt; 15 ml/min (using the Cockcroft-Gault method) within 6&#xD;
             months prior to screening. (Note: multiply estimated rate by 0.85 for women).&#xD;
&#xD;
          6. Willing and able to provide informed consent&#xD;
&#xD;
          7. Able to comply with dosing instructions for study drug administration and able to&#xD;
             complete the study schedule of assessments&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant women, women who are breast feeding or who believe they may wish to become&#xD;
             pregnant during the course of the study&#xD;
&#xD;
          2. Previous recipient of a liver transplant&#xD;
&#xD;
          3. Co-infection with human immunodeficiency virus (HIV) or hepatitis C (HCV) or hepatitis&#xD;
             D (HDV)&#xD;
&#xD;
          4. Severe or uncontrolled comorbidities, determined by the Investigator.&#xD;
&#xD;
          5. Known history of serum albumin level &lt;3 g/dL, or total bilirubin level &gt;3 mg/dL, or&#xD;
             presence of ascites.&#xD;
&#xD;
          6. Known history of hepatic encephalopathy, and/or variceal bleeding.&#xD;
&#xD;
          7. Malignancy history including hepatocellular carcinoma, except cancers curable by&#xD;
             surgical resection (e.g. basal cell skin cancer and squamous cell cancer within 5 yrs&#xD;
             of screening).&#xD;
&#xD;
          8. On any of the disallowed concomitant medications listed in the prior and concomitant&#xD;
             medications list (pg. 11). Subjects on prohibited medications who are otherwise&#xD;
             eligible will need a wash out period of at least 30 days prior to the Screening.&#xD;
&#xD;
          9. Males and females of reproductive potential who are unwilling to use &quot;effective&quot;&#xD;
             protocol-specified method(s) of contraception during the study.&#xD;
&#xD;
         10. Current substance or alcohol abuse judged by the investigator to potentially interfere&#xD;
             with subject compliance.&#xD;
&#xD;
         11. Any other clinical conditions that, in the opinion of the Investigator, would make the&#xD;
             subject unsuitable or unable to comply with any of the study procedures&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ming-Lung Yu, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kaohsiung Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ming-Lung Yu, Prof.</last_name>
    <phone>+88673121101</phone>
    <phone_ext>7475</phone_ext>
    <email>fish6069@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Kaohsiung Medical University Hospital</name>
      <address>
        <city>Kaohsiung</city>
        <zip>807</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ming-Lung Yu, DR</last_name>
      <phone>+88673121101</phone>
      <phone_ext>7475</phone_ext>
      <email>fish6069@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 24, 2018</study_first_submitted>
  <study_first_submitted_qc>January 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>April 24, 2019</last_update_submitted>
  <last_update_submitted_qc>April 24, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatitis B</keyword>
  <keyword>advanced fibrosis</keyword>
  <keyword>Cirrhosis</keyword>
  <keyword>Switch</keyword>
  <keyword>Tenofovir alafenamide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03798119
org study id: KMUHIRB-F(II)-20180111
nct id: NCT03798119
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
A total of 80 adult chronic hepatitis B patients with advanced liver fibrosis (including
      fibrosis stage 3 and cirrhosis), who are currently on nucleot(s)ide analogs (except tenofovir
      alafenamide) therapy with detectable HBV DNA after 52 weeks of therapy will switch prior NUCs
      to TAF 25 mg/day for 96 weeks
Study Overview

      Dosage regimen: Patients of CHB with advanced fibrosis and partial virological response to
      NUCs will be considered eligible for the present study. The enrollment will be up to the
      physician's discretion. The drug will be administered 1 pill (25 mg) per day orally, per
      manufacturers' instructions, and can be taken with food.

      Compliance: Enrolled patients must be monitored according to the protocol, GCP, and clinical
      practice guidelines.

      Study population: Approximately 80 adult CHB patients with advanced fibrosis (including
      fibrosis stage 3 and cirrhosis), who are currently on NUCs (except TAF) therapy with
      detectable HBV DNA after 52 weeks of therapy will switch prior NUCs to TAF 25 mg/day for 96
      weeks. For patients of fibrosis stage 3, the numbers of enrolled patients will be no more
      than 40% of total enrolled patients.

      Study Objectives

      Primary objective:

      • To describe the improvement of rate of viral suppression with TAF in patients of partial
      virological response with previous anti-HBV NUCs.

      Secondary objective

        -  To describe the persistence or improvement of rate of ALT normalization (local and AASLD
           criteria) with TAF in patients of partial virological response with previous anti-HBV
           NUCs.

        -  To describe the trends in serum creatinine, calculated creatinine clearance, and renal
           tubular function with TAF.

        -  To describe the trends in bone mineral density with TAF.

        -  To describe the progression/regression of liver fibrosis with TAF.

        -  To describe the prespecified factors associated with viral suppression and/or ALT
           normalization after switching to TAF, including viral resistance profiles, HBsAg levels
           and HBV viral loads at the initiation of prior NUC and at the time of TAF switching, HBV
           genotype, hepatic fibrosis, age, sex, prior preparations of NUCs, and host
           immunogenetics.

      Study Procedures:

      Pre-Screening: Patients who are currently under HBV NUC, except TAF therapy, with liver
      fibrosis stage 3 or 4 at the initiation of NUC, and with detectable HBV DNA after week 52 of
      therapy will be considered eligible in this prospective interventional cohort study. If the
      patient is deemed eligible to participate, the site will evaluate the potential patient using
      the inclusion/exclusion criteria and fill out the CRF for the screening visit. The local
      coordinator will transmit the pre-screening data to the central coordinator prior to the
      actual screening/baseline visit. If the patient is deemed eligible by the Primary
      Investigator, the patient will be given a study ID and allowed to enter the study.

      Screening/Baseline: Written and informed consent will be obtained prior to any study
      protocol-related procedures or data abstraction. If the patient has been pre-screened
      approved and all lab data are available, the participant will begin the study TAF treatment
      on the screening/baseline visit. The screening/baseline visit consists of obtaining written
      and informed consent, reviewing the inclusion/exclusion criteria, confirming medical history,
      completing a physical examination with vital signs and body weight, reviewing any concomitant
      medications and study drug dispensing. HCV, HDV, and HIV antibody test will be performed
      after written informed consent is obtained. The samples of HDV antibody test will be
      collected at local site and sent to KMUH, tested by central lab. Baseline resistance testing
      will also be performed by direct sequencing.

      Procedures: laboratory tests including CBC (complete blood count) panel, Serum Bilirubin
      (total/direct), AST, ALT, GGT, Albumin, BUN, Creatinine, Na, K, Phosphate, Prothrombin time
      (INR), and Urine routine/creatinine/phosphate will be done every visit. Pregnant test (only
      for women of child-bearing potential), Child-Pugh score, and FIB-4 score should also be done
      every visit. AFP (alpha-fetoprotein), and Abdominal ultrasound should also be done every 3 to
      6 months for HCC surveillance. HBV serological markers including HBeAg/HBeAb, HBV DNA
      quantification (by central lab.) will be done every visit and HBsAg quantification (by
      central lab.) every 6 months. Bone Density Scan (DEXA) will be done at week 24, 48, and 96.
      Fibroscan/CAP will be performed at week 48, and 96 to determine regression of fibrosis. Blood
      will be drawn at the site at which the participant was recruited, and processed by a lab
      technician in the clinical laboratory at that respective site, except HDV antibody test and
      HBsAg/HBV DNA quantification which will be performed by the central lab. at KMUH.

      Treatment Visits: Treatment will consist of TAF 25 mg daily with food for 96 weeks. Treatment
      visits will occur at week 4, 12, 24, 36, 48, 72, and 96 as per routine clinical care, except
      for those who developed virological breakthrough, SAE, or others judged by the investigators.
      At every visit, the patient must bring all study drugs (including empty bottles), so that the
      study coordinator can count compliance using the number of remaining pills.

      This schedule of clinic visits and laboratory tests are routine and standard practice for
      investigators in their treatment of similar patients with CHB. Patients will be encouraged to
      adhere to these recommendations. Results of these laboratory tests and clinical evaluations
      will be recorded as well as any additional evaluations that are done as part of the patient's
      clinical care that is pertinent to the objective of the study.

      Discontinuation criteria: The study can be terminated at any time for any reasons by Primary
      Investigator. Though there is no formal treatment stopping rules in this study, patients
      might be asked to stop if there are any adverse events that the investigator feels make it
      the patient's best interest to stop treatment.

      Withdrawal of Subjects

      Withdrawal Criteria:

        -  Failure to follow study instructions or protocol violation that in the judgment of the
           investigator

        -  Serious Adverse Events that in the judgment of the investigator

        -  Development of virological breakthrough (defined as reappearance of HBV DNA or at least
           one log10 elevation of HBV DNA from nadir in 2 consecutive measurements one month apart.
           further treatment plans are at the discretion of the treating physician and patient.

        -  Any medical, psychosocial or administrative or other reasons that in the judgment of the
           investigator, be detrimental to the patient's well-being.

        -  Death

        -  Withdrawal of informed consent

      Adverse Events and Toxicity Management

      Assessment of safety: Safety assessments will include monitoring of laboratory results, vital
      signs, treatment-emergent adverse events, serious adverse events, etc. Safety assessments
      will be performed at every clinic visit as part of clinical care and during follow-up visits.

      If, in Primary Investigator's judgment, a clinical significant worsening from baseline is
      observed in any laboratory or other test parameters, physical exam finding, or vital sign, a
      corresponding clinical adverse event should be recorded.

      If a specific medical diagnosis has been made, that diagnosis or syndrome should be recorded
      as the adverse event, whenever possible. However, a complete description of the signs,
      symptoms, and investigations which led to the diagnosis should be provided. For example, if
      clinically significant elevations of liver function tests are known to be secondary to
      hepatitis, "hepatitis" and not "elevated liver function tests" should be recorded. If the
      cause is not known, the abnormal test or finding should be recorded as an adverse event,
      using appropriate medical terminology (e/g/ thrombocytopenia, peripheral edema).

      Maintenance of Safety Information: Safety information will be maintained in a clinical
      database/repository in a retrievable format. At a minimum, at the end of the treatment phase
      (="last patient off treatment") as well as the end of the follow-up phase (="last patient
      out") of the study, Primary Investigator shall provide all adverse events, both serious and
      non-serious, in report format.

      Statistics

      Data management and analysis will be performed at Kaohsiung Medical University Hospital.

      Sample size to be used in the analysis: We calculated that a sample size of 80 patients with
      a 10% dropout rate would provide 85% power to show increased to 30% of virologic response
      (HBV DNA <LLOQ) rate after 52 weeks of TAF therapy, compared to 15% of continuing prior NUC
      therapy with a type I error rate of 0.05 for the one-tailed analyses of the primary endpoint.

      Statistical methods to be employed: Descriptive and comparative statistics will be performed
      for all demographic and clinical variables that are outcome endpoints for this pilot study.

      Level of significance: A 95% confidence interval will be used.

      Termination of trial: Termination of the trial will be upon completion of follow-up of all 80
      subjects enrolled and/or up to the discretion of the primary investigator.

      Procedure for missing, unused, spurious data: Data that is missing, unused or spurious data
      will all be treated as missing data. This data will be marked as an empty field.

      Deviation from the original statistical plan: Any deviation from the original statistical
      plan will be up to the discretion of the primary investigator.

      Selection of subjects to be included in analyses: All eligible subjects that have not been
      withdrawn from the study will be included in analyses.

      Interim analysis An interim analysis will be performed at Week 24 after all the 80 patients
      enrolled.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of virological response
time frame: at 48 weeks of TAF therapy.
description: HBV DNA <LLOQ
measure: Rate of virological response
time frame: at 96 weeks of treatment
description: HBV DNA <LLOQ
measure: Rate of ALT normalization
time frame: at week 48 and 96
description: by local (<40 U/L), and AASLD (male ≤35, female ≤25 U/L) criteria
measure: Changes of serum creatinine
time frame: at week 48 and 96
measure: Changes of calculated creatinine clearance (Cockcroft-Gault)
time frame: at week 48 and 96
measure: Changes in bone mineral density
time frame: at week 48 and 96
measure: Changes in liver fibrosis
time frame: at week 48 and 96
description: determined by Fibroscan
arm group label: Switch to TAF
arm group type: Experimental
description: Subjects who meet the inclusion and exclusion criteria will switch prior NUCs to TAF 25 mg/day for 96 weeks
intervention type: Drug
intervention name: Tenofovir Alafenamide
description: Subjects in this group will switch prior nucleot(s)ide analogs to Tenofovir Alafenamide 25 mg/day for 96 weeks
arm group label: Switch to TAF
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Ming-Lung Yu, Prof.
role: Principal Investigator
affiliation: Kaohsiung Medical University
last name: Ming-Lung Yu, Prof.
phone: +88673121101
phone ext: 7475
email: fish6069@gmail.com
facility: 
status: Recruiting
contact: 
country: Taiwan
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis
mesh term: Liver Cirrhosis
mesh term: Fibrosis
mesh term: Tenofovir
sharing ipd: No