<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/NCT04439539</url>
  </required_header>
  <id_info>
    <org_study_id>CR108815</org_study_id>
    <secondary_id>73763989PAHPB2005</secondary_id>
    <secondary_id>2019-004978-26</secondary_id>
    <nct_id>NCT04439539</nct_id>
  </id_info>
  <brief_title>A Study of JNJ-73763989, Pegylated Interferon Alpha-2a, Nucleos(t)Ide Analog (NA) With or Without JNJ-56136379 in Treatment-naive Participants With Hepatitis B e Antigen (HBeAg) Positive Chronic Hepatitis B Virus (HBV) Infection</brief_title>
  <official_title>A Phase 2, Randomized, Open-label, Multicenter Study to Evaluate Efficacy, Pharmacokinetics, Safety, and Tolerability of Treatment With JNJ-73763989, Pegylated Interferon Alpha-2a, Nucleos(t)Ide Analog With or Without JNJ-56136379 in Treatment-naive Patients With HBeAg Positive Chronic Hepatitis B Virus Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy of a treatment regimen of JNJ-73763989&#xD;
      + pegylated interferon alpha-2a (PegIFN-alpha-2a) + nucleos(t)ide analog (NA).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hepatitis B virus (HBV) is a small deoxyribonucleic acid virus that specifically infects the&#xD;
      human liver. The acute phase of infection is either followed by an immune controlled state or&#xD;
      progresses to chronic hepatitis B. The worldwide estimated prevalence of chronic HBV&#xD;
      infection is about 292 million people affected. Hepatitis B surface antigen (HBsAg)&#xD;
      seroclearance is currently considered to be associated with the most thorough suppression of&#xD;
      HBV replication (termed functional cure). With current available NA treatment strategies,&#xD;
      rate of HBsAg seroclearance remains very low (around 3 percent [%]) even under long-term&#xD;
      treatment. Also, with the persistently high global prevalence of HBV-associated mortality,&#xD;
      there is a medical need for more effective finite treatment options that lead to sustained&#xD;
      HBsAg seroclearance. JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous&#xD;
      injection designed to treat chronic HBV infection via a ribonucleic acid interference (RNAi)&#xD;
      mechanism. JNJ-56136379 is an orally administered capsid assembly modulator (CAM) that is&#xD;
      being developed for the treatment of chronic HBV infection. The aim of the study is to&#xD;
      evaluate the efficacy of a treatment regimen of JNJ-73763989 + PegIFN-alpha-2a + NA with or&#xD;
      without JNJ-56136379 in participants with hepatitis B e antigen (HBeAg) positive chronic&#xD;
      infection. The study will be conducted in 4 phases: a screening phase, an induction phase&#xD;
      with flexible duration, a consolidation phase with or without PegIFN-α2a and a follow-up&#xD;
      phase. Safety assessments will include Adverse Events (AEs), serious AEs of the study&#xD;
      interventions, clinical laboratory tests, Electrocardiograms (ECGs), vital signs, and&#xD;
      physical examinations. The study title reflects the original study design and JNJ-56136379&#xD;
      (JNJ-6379) was initially part of the study intervention but was discontinued as per amendment&#xD;
      6 of the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 14, 2020</start_date>
  <completion_date type="Anticipated">February 28, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 6, 2023</primary_completion_date>
  <phase>Phase 2</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>Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance 24 Weeks After Stopping all Study Interventions of Consolidation Phase and Without Restarting NA Treatment</measure>
    <time_frame>Up to Follow-up Week 24</time_frame>
    <description>Percentage of participants with HBsAg seroclearance 24 weeks after stopping all study interventions of consolidation phase and without restarting nucleos(t)ide analog (NA) treatment will be reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse Events (AEs) and Serious AEs</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Clinically Significant Abnormalities in Laboratory Parameters</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Number of participants with clinically significant abnormalities in laboratory parameters (hematology, blood biochemistry, blood coagulation, urinalysis, urine chemistry, and renal biomarkers) will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Clinically Significant Abnormalities in Electrocardiogram (ECGs)</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Number of participants with clinically significant abnormalities in electrocardiogram (ECGs) will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Clinically Significant Abnormalities in Vital Signs</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Number of participants with clinically significant abnormalities in vital signs (systolic and diastolic blood pressure, pulse rate, and body temperature) will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Clinically Significant Abnormalities in Physical Examination</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Number of participants with clinically significant abnormalities in physical examination will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Reaching HBsAg less than (&lt;) 10 IU/mL at the End of Induction Phase (Week 36)</measure>
    <time_frame>Up to Week 48</time_frame>
    <description>Percentage of participants reaching HBsAg &lt;10 international units per milliliter (IU/mL) at the end of induction phase (Week 36) will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Hepatitis B Surface Antigen (HBsAG) &lt; 10 IU/mL</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Time to Reach HBsAG &lt; 10 IU/mL will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Meeting NA Treatment Completion Criteria at the end of Consolidation Phase</measure>
    <time_frame>Up to Week 60</time_frame>
    <description>Percentage of participants meeting NA treatment completion criteria at the end of consolidation phase will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Percentage of participants with HBsAg Seroclearance will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with HBV DNA less than (&lt;) Lower Limit of Quantification (LLOQ)</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Percentage of participants with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) &lt;LLOQ will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Flares</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Number of participants with flares (virologic, biochemical and clinical flares) will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Requiring NA Re-treatment</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Percentage of participants requiring NA re-treatment based on failure in NA treatment completion criteria will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Percentage of participants with (sustained) reduction, suppression, and/or seroclearance considering single and multiple markers (such as hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], HBV DNA and alanine aminotransferase [ALT]) will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) and Hepatitis B e Antigen (HBeAg) Seroconversion</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Percentage of participants with HBsAg and HBeAg seroconversion will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Achieve Hepatitis B Surface Antigen (HBsAg) Seroclearance</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Time to achieve HBsAg seroclearance will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Achieve Hepatitis B e Antigen (HBeAg) Seroclearance</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Time to achieve hepatitis B e antigen (HBeAg) seroclearance will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Achieve Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) &lt;LLOQ</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Time to achieve HBV DNA &lt;LLOQ will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants with Hepatitis B e Antigen (HBeAg), Hepatitis B Surface Antigen (HBsAg), and Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Percentage of participants with HBeAg, HBsAg, and HBV DNA Levels will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Hepatitis B e Antigen (HBeAg)</measure>
    <time_frame>Baseline and Week 102</time_frame>
    <description>Change from baseline in HBeAg will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Hepatitis B Surface Antigen (HBsAg)</measure>
    <time_frame>Baseline and Week 102</time_frame>
    <description>Change from baseline in HBsAg will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels</measure>
    <time_frame>Baseline and Week 102</time_frame>
    <description>Change from baseline in HBV DNA levels will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Virologic Breakthrough</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Percentage of participants with virologic breakthrough (defined as confirmed on-treatment HBV DNA increase by greater than (&gt;) 1 log10 IU/mL from nadir level or confirmed on treatment level &gt;200 IU/mL in participants who had HBV DNA level below &lt;LLOQ of the HBV DNA assay) will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants who Reach Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Undetectability After Re-start of NA Treatment During Follow-up</measure>
    <time_frame>Up to Week 102</time_frame>
    <description>Percentage of participants who reach HBV DNA undetectability after re-start of NA treatment during follow-up will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax)</measure>
    <time_frame>Up to Day 253 postdose</time_frame>
    <description>Cmax is the maximum observed plasma concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours [AUC (0- 24 hours)]</measure>
    <time_frame>Up to 24 hours postdose</time_frame>
    <description>AUC (0- 24 hours) is the area under the plasma concentration-time curve from time zero to 24 hours.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Hepatitis B, Chronic</condition>
  <arm_group>
    <arm_group_label>Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During the Induction phase, participants will receive JNJ-73763989 subcutaneously along with JNJ-56136379 tablet orally with NA (either tenofovir disoproxil or tenofovir alafenamide tablets orally) treatment. At the start of consolidation phase, participants will be randomized to receive PegIFN-alpha-2a subcutaneously in addition to JNJ-73763989 and JNJ-56136379 with NA in arm 1 and arm 2 (without PegIFN-alpha-2a). According to predefined criteria NA treatment may be continued during the follow up (FU) phase.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Following implementation of protocol amendment- 5 and 6, all participants will receive JNJ-73763989 subcutaneously along with NA (tenofovir disoproxil tablets orally) for 36 weeks (induction phase). In the consolidation phase, participants will receive PegIFN-alpha-2a subcutaneously in addition to JNJ-73763989 and NA for 12 weeks. According to predefined criteria NA treatment may be continued during the follow up (FU) phase. JNJ-56136379 (JNJ-6379) was discontinued as per amendment 6 of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>JNJ-73763989</intervention_name>
    <description>JNJ-73763989 injection will be administered subcutaneously.</description>
    <arm_group_label>Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect</arm_group_label>
    <arm_group_label>Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect</arm_group_label>
    <other_name>JNJ-3989</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PegIFN-alpha-2a</intervention_name>
    <description>PegIFN-alpha-2a injection will be administered subcutaneously.</description>
    <arm_group_label>Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect</arm_group_label>
    <arm_group_label>Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir disoproxil</intervention_name>
    <description>Tenofovir disoproxil film-coated tablet will be administered orally.</description>
    <arm_group_label>Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect</arm_group_label>
    <arm_group_label>Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir alafenamide</intervention_name>
    <description>Tenofovir alafenamide film-coated tablet will be administered orally.</description>
    <arm_group_label>Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>JNJ-56136379</intervention_name>
    <description>JNJ-56136379 will be administered orally.</description>
    <arm_group_label>Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect</arm_group_label>
    <other_name>JNJ-6379</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Medically stable based on physical examination, medical history, vital signs,&#xD;
             laboratory values, and 12-lead Electrocardiogram (ECG) at screening&#xD;
&#xD;
          -  Currently not treated chronic hepatitis B virus (HBV) infection with alanine&#xD;
             transaminase (ALT) less than (&lt;) 2* upper limit of normal (ULN) at screening and HBV&#xD;
             deoxyribonucleic acid (DNA) greater than or equal to (&gt;=) 20,000 international units&#xD;
             per milliliter (IU/mL)&#xD;
&#xD;
          -  Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2),&#xD;
             extremes included&#xD;
&#xD;
          -  Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than or equal to (&lt;=) 9&#xD;
             Kilopascal (kPa) at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of infection with hepatitis A, C, D or E virus infection or evidence of human&#xD;
             immunodeficiency, virus type 1 (HIV-1) or HIV-2 infection at screening&#xD;
&#xD;
          -  History or evidence of clinical signs or symptoms of hepatic decompensation, including&#xD;
             but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal&#xD;
             varices&#xD;
&#xD;
          -  Evidence of liver disease of non-HBV etiology&#xD;
&#xD;
          -  Participants with a history of malignancy within 5 years before screening&#xD;
&#xD;
          -  Participants who had or planned major surgery, (example, requiring general anesthesia)&#xD;
             or who have received an organ transplant&#xD;
&#xD;
          -  Contraindications to the use of PegIFN-α2a&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ruane Clinical Research Group Inc</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90036</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Center For Liver Diseases</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liver Institute Northwest</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4Z6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GI Research Institute (G.I.R.I.)</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6Z 2K5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vancouver ID Research and Care Centre Society</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6Z2C7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto General Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>ON M5G 2C4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Beaujon</name>
      <address>
        <city>Clichy</city>
        <zip>92110</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Grenoble - Hopital Albert Michallon</name>
      <address>
        <city>Grenoble</city>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital de La Croix Rousse</name>
      <address>
        <city>Lyon</city>
        <zip>69004</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nantes - Hotel Dieu</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Hopital Saint Antoine</name>
      <address>
        <city>Paris</city>
        <zip>75012</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Rennes - Hopital Pontchaillou</name>
      <address>
        <city>Rennes</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nancy Brabois</name>
      <address>
        <city>Vandoeuvre les Nancy</city>
        <zip>54511</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH</name>
      <address>
        <city>Berlin</city>
        <zip>10439</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Essen</name>
      <address>
        <city>Essen</city>
        <zip>45122</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1</name>
      <address>
        <city>Frankfurt</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover</name>
      <address>
        <city>Hannover</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hiroshima University Hospital</name>
      <address>
        <city>Hiroshima-shi</city>
        <zip>734-8551</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nara Medical University Hospital</name>
      <address>
        <city>Kashihara</city>
        <zip>634-8522</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Musashino Red Cross Hospital</name>
      <address>
        <city>Musashino</city>
        <zip>180-8610</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nagoya City University Hospital</name>
      <address>
        <city>Nagoya</city>
        <zip>467-8602</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yokohama City University Medical Center</name>
      <address>
        <city>Yokohama</city>
        <zip>232-0024</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Irkutsk State Medical University</name>
      <address>
        <city>Irkutsk</city>
        <zip>664003</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Republic Clinical Infectious Hospital n.a. AF Agafonov</name>
      <address>
        <city>Kazan</city>
        <zip>420140</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>190103</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Infectious Diseases Hospital n. a. S.P. Botkin</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>195067</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Company Hepatolog Ltd</name>
      <address>
        <city>Samara</city>
        <zip>443045</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Smolensk Regional Clinical Hospital</name>
      <address>
        <city>Smolensk</city>
        <zip>214018</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stavropol State Medical University</name>
      <address>
        <city>Stavropol</city>
        <zip>355017</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Clinic I Provincial de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>8028</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Univ. Vall D Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>8035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Gral. Univ. Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaohsiung Medical University Chung-Ho Memorial Hospital</name>
      <address>
        <city>Kaohsiung</city>
        <zip>80756</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <zip>40447</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cheng Kung University Hospital</name>
      <address>
        <city>Tainan</city>
        <zip>70403</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hacettepe University Hospital</name>
      <address>
        <city>Ankara</city>
        <zip>06230</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istanbul University Cerrahpasa Medical Faculty</name>
      <address>
        <city>Istanbul</city>
        <zip>34098</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Umraniye Training and Research Hospital</name>
      <address>
        <city>Istanbul</city>
        <zip>34764</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ege University Medical of Faculty, Department of Gastroenterology</name>
      <address>
        <city>Izmir</city>
        <zip>35100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acibadem Mehmet Ali Aydinlar University</name>
      <address>
        <city>Kucukcekmece</city>
        <zip>34303</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karadeniz Teknik University Medical Faculty</name>
      <address>
        <city>Trabzon</city>
        <zip>61080</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHS Greater Glasgow and Clyde - Gartnavel General Hospital</name>
      <address>
        <city>Glasgow</city>
        <zip>G12 0YN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Glasgow Royal Infirmary</name>
      <address>
        <city>Glasgow</city>
        <zip>G31 2ER</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>Kings College Hospital</name>
      <address>
        <city>London</city>
        <zip>SE5 9RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Japan</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>JNJ-56136379</mesh_term>
    <mesh_term>Peginterferon alfa-2a</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) project site at yoda.yale.edu</ipd_description>
    <ipd_url>https://www.janssen.com/clinical-trials/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/NCT04439539
org study id: CR108815
secondary id: 73763989PAHPB2005
secondary id: 2019-004978-26
nct id: NCT04439539
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the efficacy of a treatment regimen of JNJ-73763989
      + pegylated interferon alpha-2a (PegIFN-alpha-2a) + nucleos(t)ide analog (NA).
Hepatitis B virus (HBV) is a small deoxyribonucleic acid virus that specifically infects the
      human liver. The acute phase of infection is either followed by an immune controlled state or
      progresses to chronic hepatitis B. The worldwide estimated prevalence of chronic HBV
      infection is about 292 million people affected. Hepatitis B surface antigen (HBsAg)
      seroclearance is currently considered to be associated with the most thorough suppression of
      HBV replication (termed functional cure). With current available NA treatment strategies,
      rate of HBsAg seroclearance remains very low (around 3 percent [%]) even under long-term
      treatment. Also, with the persistently high global prevalence of HBV-associated mortality,
      there is a medical need for more effective finite treatment options that lead to sustained
      HBsAg seroclearance. JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous
      injection designed to treat chronic HBV infection via a ribonucleic acid interference (RNAi)
      mechanism. JNJ-56136379 is an orally administered capsid assembly modulator (CAM) that is
      being developed for the treatment of chronic HBV infection. The aim of the study is to
      evaluate the efficacy of a treatment regimen of JNJ-73763989 + PegIFN-alpha-2a + NA with or
      without JNJ-56136379 in participants with hepatitis B e antigen (HBeAg) positive chronic
      infection. The study will be conducted in 4 phases: a screening phase, an induction phase
      with flexible duration, a consolidation phase with or without PegIFN-α2a and a follow-up
      phase. Safety assessments will include Adverse Events (AEs), serious AEs of the study
      interventions, clinical laboratory tests, Electrocardiograms (ECGs), vital signs, and
      physical examinations. The study title reflects the original study design and JNJ-56136379
      (JNJ-6379) was initially part of the study intervention but was discontinued as per amendment
      6 of the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance 24 Weeks After Stopping all Study Interventions of Consolidation Phase and Without Restarting NA Treatment
time frame: Up to Follow-up Week 24
description: Percentage of participants with HBsAg seroclearance 24 weeks after stopping all study interventions of consolidation phase and without restarting nucleos(t)ide analog (NA) treatment will be reported.
measure: Number of Participants with Adverse Events (AEs) and Serious AEs
time frame: Up to Week 102
description: An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
measure: Number of Participants with Clinically Significant Abnormalities in Laboratory Parameters
time frame: Up to Week 102
description: Number of participants with clinically significant abnormalities in laboratory parameters (hematology, blood biochemistry, blood coagulation, urinalysis, urine chemistry, and renal biomarkers) will be reported.
measure: Number of Participants with Clinically Significant Abnormalities in Electrocardiogram (ECGs)
time frame: Up to Week 102
description: Number of participants with clinically significant abnormalities in electrocardiogram (ECGs) will be reported.
measure: Number of Participants with Clinically Significant Abnormalities in Vital Signs
time frame: Up to Week 102
description: Number of participants with clinically significant abnormalities in vital signs (systolic and diastolic blood pressure, pulse rate, and body temperature) will be reported.
measure: Number of Participants with Clinically Significant Abnormalities in Physical Examination
time frame: Up to Week 102
description: Number of participants with clinically significant abnormalities in physical examination will be reported.
measure: Percentage of Participants Reaching HBsAg less than (<) 10 IU/mL at the End of Induction Phase (Week 36)
time frame: Up to Week 48
description: Percentage of participants reaching HBsAg <10 international units per milliliter (IU/mL) at the end of induction phase (Week 36) will be reported.
measure: Time to Reach Hepatitis B Surface Antigen (HBsAG) < 10 IU/mL
time frame: Up to Week 102
description: Time to Reach HBsAG < 10 IU/mL will be reported.
measure: Percentage of Participants Meeting NA Treatment Completion Criteria at the end of Consolidation Phase
time frame: Up to Week 60
description: Percentage of participants meeting NA treatment completion criteria at the end of consolidation phase will be reported.
measure: Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance
time frame: Up to Week 102
description: Percentage of participants with HBsAg Seroclearance will be reported.
measure: Percentage of Participants with HBV DNA less than (<) Lower Limit of Quantification (LLOQ)
time frame: Up to Week 102
description: Percentage of participants with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) <LLOQ will be reported.
measure: Number of Participants with Flares
time frame: Up to Week 102
description: Number of participants with flares (virologic, biochemical and clinical flares) will be reported.
measure: Percentage of Participants Requiring NA Re-treatment
time frame: Up to Week 102
description: Percentage of participants requiring NA re-treatment based on failure in NA treatment completion criteria will be reported.
measure: Percentage of Participants with (Sustained) Reduction, Suppression, and/or Seroclearance
time frame: Up to Week 102
description: Percentage of participants with (sustained) reduction, suppression, and/or seroclearance considering single and multiple markers (such as hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], HBV DNA and alanine aminotransferase [ALT]) will be reported.
measure: Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) and Hepatitis B e Antigen (HBeAg) Seroconversion
time frame: Up to Week 102
description: Percentage of participants with HBsAg and HBeAg seroconversion will be reported.
measure: Time to Achieve Hepatitis B Surface Antigen (HBsAg) Seroclearance
time frame: Up to Week 102
description: Time to achieve HBsAg seroclearance will be reported.
measure: Time to Achieve Hepatitis B e Antigen (HBeAg) Seroclearance
time frame: Up to Week 102
description: Time to achieve hepatitis B e antigen (HBeAg) seroclearance will be reported.
measure: Time to Achieve Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <LLOQ
time frame: Up to Week 102
description: Time to achieve HBV DNA <LLOQ will be reported.
measure: Percentage of participants with Hepatitis B e Antigen (HBeAg), Hepatitis B Surface Antigen (HBsAg), and Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels
time frame: Up to Week 102
description: Percentage of participants with HBeAg, HBsAg, and HBV DNA Levels will be reported.
measure: Change from Baseline in Hepatitis B e Antigen (HBeAg)
time frame: Baseline and Week 102
description: Change from baseline in HBeAg will be reported.
measure: Change from Baseline in Hepatitis B Surface Antigen (HBsAg)
time frame: Baseline and Week 102
description: Change from baseline in HBsAg will be reported.
measure: Change from Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels
time frame: Baseline and Week 102
description: Change from baseline in HBV DNA levels will be reported.
measure: Percentage of Participants with Virologic Breakthrough
time frame: Up to Week 102
description: Percentage of participants with virologic breakthrough (defined as confirmed on-treatment HBV DNA increase by greater than (>) 1 log10 IU/mL from nadir level or confirmed on treatment level >200 IU/mL in participants who had HBV DNA level below <LLOQ of the HBV DNA assay) will be reported.
measure: Percentage of Participants who Reach Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Undetectability After Re-start of NA Treatment During Follow-up
time frame: Up to Week 102
description: Percentage of participants who reach HBV DNA undetectability after re-start of NA treatment during follow-up will be reported.
measure: Maximum Observed Plasma Concentration (Cmax)
time frame: Up to Day 253 postdose
description: Cmax is the maximum observed plasma concentration.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours [AUC (0- 24 hours)]
time frame: Up to 24 hours postdose
description: AUC (0- 24 hours) is the area under the plasma concentration-time curve from time zero to 24 hours.
arm group label: Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect
arm group type: Experimental
description: During the Induction phase, participants will receive JNJ-73763989 subcutaneously along with JNJ-56136379 tablet orally with NA (either tenofovir disoproxil or tenofovir alafenamide tablets orally) treatment. At the start of consolidation phase, participants will be randomized to receive PegIFN-alpha-2a subcutaneously in addition to JNJ-73763989 and JNJ-56136379 with NA in arm 1 and arm 2 (without PegIFN-alpha-2a). According to predefined criteria NA treatment may be continued during the follow up (FU) phase.
arm group label: Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect
arm group type: Experimental
description: Following implementation of protocol amendment- 5 and 6, all participants will receive JNJ-73763989 subcutaneously along with NA (tenofovir disoproxil tablets orally) for 36 weeks (induction phase). In the consolidation phase, participants will receive PegIFN-alpha-2a subcutaneously in addition to JNJ-73763989 and NA for 12 weeks. According to predefined criteria NA treatment may be continued during the follow up (FU) phase. JNJ-56136379 (JNJ-6379) was discontinued as per amendment 6 of the study.
intervention type: Drug
intervention name: JNJ-73763989
description: JNJ-73763989 injection will be administered subcutaneously.
arm group label: Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect
arm group label: Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect
other name: JNJ-3989
intervention type: Drug
intervention name: PegIFN-alpha-2a
description: PegIFN-alpha-2a injection will be administered subcutaneously.
arm group label: Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect
arm group label: Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect
intervention type: Drug
intervention name: Tenofovir disoproxil
description: Tenofovir disoproxil film-coated tablet will be administered orally.
arm group label: Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect
arm group label: Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect
intervention type: Drug
intervention name: Tenofovir alafenamide
description: Tenofovir alafenamide film-coated tablet will be administered orally.
arm group label: Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect
intervention type: Drug
intervention name: JNJ-56136379
description: JNJ-56136379 will be administered orally.
arm group label: Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect
other name: JNJ-6379
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
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country: Canada
country: France
country: Germany
country: Japan
country: Russian Federation
country: Spain
country: Taiwan
country: Turkey
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: Tenofovir
mesh term: JNJ-56136379
mesh term: Peginterferon alfa-2a
sharing ipd: Yes
ipd description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) project site at yoda.yale.edu
ipd url: https://www.janssen.com/clinical-trials/transparency