<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/NCT01671787</url>
  </required_header>
  <id_info>
    <org_study_id>GS-US-320-0101</org_study_id>
    <nct_id>NCT01671787</nct_id>
  </id_info>
  <brief_title>A Phase 1b Study Assessing GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B</brief_title>
  <official_title>A Phase 1b Randomized, Open Label, Active-Controlled Study to Assess the Safety, Viral Kinetics, and Anti-HBV Activity of GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B (CHB) Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gilead Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label study evaluating multiple doses of GS-7340 versus Tenofovir disoproxil&#xD;
      fumarate (TDF).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, open-label, active-controlled study whose primary objective is to&#xD;
      evaluate the safety and efficacy of several doses of GS-7340. This study will evaluate the&#xD;
      safety, viral kinetics, and antiviral activity of 4 different doses of GS-7340 over 28 days&#xD;
      of therapy. In addition, the study will evaluate the antiviral activity of an optimal dose of&#xD;
      GS-7340 versus 300mg Tenofovir disoproxil fumarate (TDF) over 28 days of therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2012</start_date>
  <completion_date type="Actual">April 2013</completion_date>
  <primary_completion_date type="Actual">April 2013</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in serum hepatitis B virus (HBV) DNA</measure>
    <time_frame>Up to Week 4</time_frame>
    <description>Time-weighted average change from baseline through Week 4 (DAVG4) in serum HBV DNA (log10 IU/mL) for GS-7340 8-, 25-, 40 and 120-mg.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in HBV DNA for tenofovir disoproxil fumarate (TDF)</measure>
    <time_frame>Up to Week 4</time_frame>
    <description>Comparing the short-term antiviral activity of GS-7340 with TDF 300mg. This is measured by time-weighted average change from baseline through Week 4 (DAVG4) in serum HBV DNA (log10 IU/mL) for TDF.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in HBV DNA of GS-7340 through 28 days of therapy</measure>
    <time_frame>Up to week 4</time_frame>
    <description>Time weighted change from baseline to day 29 (DAVG4) in serum HBV DNA (log10 IU/mL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of GS-7340 and/or tenofovir (TVF) following single and multiple doses of GS-7340 and TDF</measure>
    <time_frame>Up to week 4</time_frame>
    <description>GS-7340 and tenofovir (TFV) PK parameters in plasma will be calculated as applicable: Cmax, Tmax, Clast, Tlast, T1/2, λz, AUC0-t, AUC0-last, AUC0-∞, %AUCexp.&#xD;
PK samples are collected on:&#xD;
Baseline/Day 1: 0 (predose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose&#xD;
Additional predose plasma samples will be collected on Days 2, 5, 8, 10, 15, 19, 22, and 29/End of Treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and Tolerability of Therapy</measure>
    <time_frame>Up to week 4</time_frame>
    <description>Safety and tolerability is measured by the incidence of adverse events and graded laboratory abnormalities</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">51</enrollment>
  <condition>Chronic Hepatitis B</condition>
  <arm_group>
    <arm_group_label>GS-7340 8mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GS-7340 25mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GS-7340 40mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GS-7340 120mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tenofovir disoproxil fumarate 300mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GS-7340</intervention_name>
    <description>Subjects are randomized to receive one of four different doses of GS-7340 over 28 days of therapy.</description>
    <arm_group_label>GS-7340 120mg</arm_group_label>
    <arm_group_label>GS-7340 25mg</arm_group_label>
    <arm_group_label>GS-7340 40mg</arm_group_label>
    <arm_group_label>GS-7340 8mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir disoproxil fumarate</intervention_name>
    <description>Subjects will receive 300mg of Tenofovir disoproxil fumarate (TDF) over 28 days of therapy</description>
    <arm_group_label>Tenofovir disoproxil fumarate 300mg</arm_group_label>
    <other_name>Viread</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must be between 18 and 65 years of age&#xD;
&#xD;
          -  Must have Screening plasma HBV DNA ≥ 2x10^3 IU/mL&#xD;
&#xD;
          -  Must have chronic HBV infection for at least 6 months&#xD;
&#xD;
          -  Must have estimated creatinine clearance (CLCr) ≥ 70 mL/min&#xD;
&#xD;
          -  Not pregnant or nursing&#xD;
&#xD;
          -  Women must be of non-childbearing potential OR of childbearing potential with&#xD;
             confirmed negative pregnancy tests&#xD;
&#xD;
          -  Consistent and correct use of recommended methods of birth control for men and women&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating subjects&#xD;
&#xD;
          -  Receipt of anti-HBV nucleoside/nucleotide therapy. Subjects who have failed prior&#xD;
             Interferon treatment, greater than 6 months prior to screening, are permitted to&#xD;
             participate in the study screening&#xD;
&#xD;
          -  Known co-infection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)&#xD;
&#xD;
          -  Presence of autoimmune disorders&#xD;
&#xD;
          -  History of liver disease other than Hepatitis B&#xD;
&#xD;
          -  History of Gilbert's Disease&#xD;
&#xD;
          -  Any sign of decompensated liver disease&#xD;
&#xD;
          -  Known or suspected cirrhosis&#xD;
&#xD;
          -  Evidence of hepatocellular carcinoma&#xD;
&#xD;
          -  Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac&#xD;
             conduction abnormalities&#xD;
&#xD;
          -  Electrolyte abnormalities&#xD;
&#xD;
          -  History of treatment that permanently alters the gastric condition&#xD;
&#xD;
          -  Alcohol or substance abuse&#xD;
&#xD;
          -  History of bleeding diathesis&#xD;
&#xD;
          -  Significant bone disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Flaherty, MD</last_name>
    <role>Study Director</role>
    <affiliation>Gilead Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research and Education Inc.</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland Institute of Human Virology</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Health System</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine - St. Luke's Episcopal Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Medical Centre</name>
      <address>
        <city>Melborne</city>
        <state>Victoria</state>
        <zip>03168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alfred Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Health</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linear Clinical Research Ltd</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Downtown Infectious Diseases Clinic (University of British Columbia)</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6Z2C9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ottawa Hospital, General Campus</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto General Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2C4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Algorithme Pharma</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3P3P1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pro-recherche</name>
      <address>
        <city>St. Romuald</city>
        <state>Quebec</state>
        <zip>G6W 8H1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Auckland Clinical Studies</name>
      <address>
        <city>Auckland</city>
        <zip>1042</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Birmingham NHS Foundation Trust</name>
      <address>
        <city>Birmingham</city>
        <zip>B152TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grahame Hayton Unit</name>
      <address>
        <city>London</city>
        <zip>E1 1BB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London Hospital</name>
      <address>
        <city>London</city>
        <zip>NW1-2BU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Liver Studies, King's College Hospital</name>
      <address>
        <city>London</city>
        <zip>SE5 9RS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nottingham University Hospitals NHS Trust - Queens Medical Centre</name>
      <address>
        <city>Nottingham</city>
        <zip>NG7 2UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Canada</country>
    <country>New Zealand</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2014</verification_date>
  <study_first_submitted>August 21, 2012</study_first_submitted>
  <study_first_submitted_qc>August 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 24, 2012</study_first_posted>
  <last_update_submitted>October 19, 2018</last_update_submitted>
  <last_update_submitted_qc>October 19, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatitis B</keyword>
  <keyword>HBV</keyword>
  <keyword>GS-7340</keyword>
  <keyword>TDF</keyword>
  <keyword>Tenofovir disoproxil fumarate</keyword>
  <keyword>Gilead</keyword>
  <keyword>Viread</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 B, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Hepatitis, Chronic</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>Yes</sharing_ipd>
    <ipd_description>Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>18 months after study completion</ipd_time_frame>
    <ipd_access_criteria>A secured external environment with username, password, and RSA code.</ipd_access_criteria>
    <ipd_url>http://www.gilead.com/research/disclosure-and-transparency</ipd_url>
  </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/NCT01671787
org study id: GS-US-320-0101
nct id: NCT01671787
lead sponsor: 
has dmc: No
This is an open-label study evaluating multiple doses of GS-7340 versus Tenofovir disoproxil
      fumarate (TDF).
This is a randomized, open-label, active-controlled study whose primary objective is to
      evaluate the safety and efficacy of several doses of GS-7340. This study will evaluate the
      safety, viral kinetics, and antiviral activity of 4 different doses of GS-7340 over 28 days
      of therapy. In addition, the study will evaluate the antiviral activity of an optimal dose of
      GS-7340 versus 300mg Tenofovir disoproxil fumarate (TDF) over 28 days of therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in serum hepatitis B virus (HBV) DNA
time frame: Up to Week 4
description: Time-weighted average change from baseline through Week 4 (DAVG4) in serum HBV DNA (log10 IU/mL) for GS-7340 8-, 25-, 40 and 120-mg.
measure: Change in HBV DNA for tenofovir disoproxil fumarate (TDF)
time frame: Up to Week 4
description: Comparing the short-term antiviral activity of GS-7340 with TDF 300mg. This is measured by time-weighted average change from baseline through Week 4 (DAVG4) in serum HBV DNA (log10 IU/mL) for TDF.
measure: Change in HBV DNA of GS-7340 through 28 days of therapy
time frame: Up to week 4
description: Time weighted change from baseline to day 29 (DAVG4) in serum HBV DNA (log10 IU/mL)
measure: Pharmacokinetics (PK) of GS-7340 and/or tenofovir (TVF) following single and multiple doses of GS-7340 and TDF
time frame: Up to week 4
description: GS-7340 and tenofovir (TFV) PK parameters in plasma will be calculated as applicable: Cmax, Tmax, Clast, Tlast, T1/2, λz, AUC0-t, AUC0-last, AUC0-∞, %AUCexp.
PK samples are collected on:
Baseline/Day 1: 0 (predose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
Additional predose plasma samples will be collected on Days 2, 5, 8, 10, 15, 19, 22, and 29/End of Treatment.
measure: Safety and Tolerability of Therapy
time frame: Up to week 4
description: Safety and tolerability is measured by the incidence of adverse events and graded laboratory abnormalities
arm group label: GS-7340 8mg
arm group type: Experimental
description: After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
arm group label: GS-7340 25mg
arm group type: Experimental
description: After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
arm group label: GS-7340 40mg
arm group type: Experimental
description: After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
arm group label: GS-7340 120mg
arm group type: Experimental
description: After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
arm group label: Tenofovir disoproxil fumarate 300mg
arm group type: Experimental
description: After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
intervention type: Drug
intervention name: GS-7340
description: Subjects are randomized to receive one of four different doses of GS-7340 over 28 days of therapy.
arm group label: GS-7340 120mg
arm group label: GS-7340 25mg
arm group label: GS-7340 40mg
arm group label: GS-7340 8mg
intervention type: Drug
intervention name: Tenofovir disoproxil fumarate
description: Subjects will receive 300mg of Tenofovir disoproxil fumarate (TDF) over 28 days of therapy
arm group label: Tenofovir disoproxil fumarate 300mg
other name: Viread
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: John Flaherty, MD
role: Study Director
affiliation: Gilead Sciences
facility: 
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country: Australia
country: Canada
country: New Zealand
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Hepatitis, Chronic
mesh term: Tenofovir
sharing ipd: Yes
ipd description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: 18 months after study completion
ipd access criteria: A secured external environment with username, password, and RSA code.
ipd url: http://www.gilead.com/research/disclosure-and-transparency