<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/NCT02263079</url>
  </required_header>
  <id_info>
    <org_study_id>NV25361</org_study_id>
    <secondary_id>2006-000977-31</secondary_id>
    <nct_id>NCT02263079</nct_id>
  </id_info>
  <brief_title>A Study of Pegylated Interferon Alfa-2A in Combination With Lamivudine or Entecavir Compared With Untreated Control Group in Children With Hepatitis B Envelope Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB) in the Immune-Tolerant Phase</brief_title>
  <official_title>A Phase IIIb, Randomized, Open-Label Study of Pegylated Interferon Alfa-2A in Combination With Lamivudine or Entecavir Compared With Untreated Control Patients in Children With HBeAg Positive Chronic Hepatitis B in the Immune-Tolerant Phase</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized, controlled, parallel group, open-label multicenter study will evaluate the&#xD;
      efficacy and safety of a combination of pegylated interferon alfa-2A (Pegasys) plus&#xD;
      lamivudine or entecavir compared with an untreated control group in participants with HBeAg&#xD;
      positive CHB in the immune tolerant phase. NOTE: STUDY RECRUITMENT HAS BEEN TERMINATED&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 16, 2014</start_date>
  <completion_date type="Actual">January 29, 2020</completion_date>
  <primary_completion_date type="Actual">January 29, 2020</primary_completion_date>
  <phase>Phase 3</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 Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation</measure>
    <time_frame>24 weeks post-treatment/at the end of untreated observation (Week 80)</time_frame>
    <description>This endpoint is defined as loss of HBsAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80). The percentage of responders (response rate) and 95% CI (using the Clopper-Pearson method) for the response rate are presented for each group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Loss of HBsAg</measure>
    <time_frame>1 year post-end of treatment (End of treatment = Week 56)</time_frame>
    <description>This endpoint is defined as loss of HBsAg at 1 year post-treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg)</measure>
    <time_frame>24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)</time_frame>
    <description>This endpoint is defined as loss of HBeAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs</measure>
    <time_frame>24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)</time_frame>
    <description>This endpoint measures the seroconversion to anti-HBs defined as loss of HBsAg and presence of anti-HBs at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe</measure>
    <time_frame>24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)</time_frame>
    <description>This endpoint measures the seroconversion to anti-HBe defined as loss of HBeAg and presence of anti-HBe at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [&lt;] 20,000 International Units Per Milliliter [IU/mL], &lt; 2000 IU/mL, or Undetectable HBV DNA)</measure>
    <time_frame>24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)</time_frame>
    <description>This endpoint measures different HBV DNA levels (&lt;20000 IU/mL, &lt;2000 IU/mL and undetectable) measured by PCR or hybridization at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-treatment in the treated group. HBV-DNA undetectable is defined as &lt;29 IU/mL. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm</measure>
    <time_frame>Baseline, Week 8, 20, 32, 44, 56, Follow up Week 4 and 24</time_frame>
    <description>This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Peg-INF-Alfa-2A + Lamivudine or Entecavir arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in HBV DNA Levels in the Untreated Control Participants</measure>
    <time_frame>Baseline, Week 32, 56 and end of untreated observation (Week 80)</time_frame>
    <description>This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Untreated Control arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels &lt;20,000 IU/mL</measure>
    <time_frame>24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)</time_frame>
    <description>This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels &lt;20,000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels &lt;2000 IU/mL</measure>
    <time_frame>24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)</time_frame>
    <description>This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels &lt;2000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Adverse Events (AEs)</measure>
    <time_frame>Baseline up to 24 weeks post-treatment/end of untreated observation (Week 80)</time_frame>
    <description>An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With AEs Leading to Dose Modification or Interruption</measure>
    <time_frame>Baseline up to 24 weeks post-end of treatment</time_frame>
    <description>This endpoint measures AEs and lab abnormalities leading to dose interruption or dose modification. Does modification included dose reduced, dose increased or drug interrupted. Adverse events included laboratory abnormalities reported as adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Concentration of Peg-INF-Alfa-2A</measure>
    <time_frame>At Weeks 12, 16, 20, 32, 44, 56</time_frame>
    <description>The serum concentration of Peg-INF-Alfa-2A was measured in picogram/milliliter.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Pediatric Immuno-Tolerant Chronic Hepatitis B</condition>
  <arm_group>
    <arm_group_label>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Untreated Control Participants</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Untreated control participants will be observed up to 80 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Peg-INF-Alfa-2A Monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive Peginterferon Alfa 2A subcutaneously once weekly with dosing based on body surface area (BSA) categories for 48 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Entecavir</intervention_name>
    <description>Participants will receive entecavir, either as a film-coated tablet or oral solution, once daily at a dose of 0.015 milligrams per kilogram (mg/kg) (maximum daily dose of 0.5 mg).</description>
    <arm_group_label>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lamivudine</intervention_name>
    <description>Participants will receive lamivudine, either as a film-coated tablet or oral solution, once daily at a dose of 3 mg/kg (maximum daily dose of 100 mg).</description>
    <arm_group_label>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegylated Interferon Alfa-2A</intervention_name>
    <description>Participants will receive pegylated interferon-alfa-2A at a body surface area (BSA) based dose of 180 micrograms per 1.73 square meter (mcg/1.73m^2) BSA.</description>
    <arm_group_label>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</arm_group_label>
    <arm_group_label>Peg-INF-Alfa-2A Monotherapy</arm_group_label>
    <other_name>Pegasys, Peg-IFN-Alfa-2A</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Positive for HBsAg and HBeAg for more than 6 months prior to baseline&#xD;
&#xD;
          -  Detectable HBV-DNA (&gt;20,000 IU/mL) as measured by polymerization chain reaction (PCR)&#xD;
             or hybridization on at least 2 occasions at least one month apart with the latest&#xD;
             determination obtained less than or equal to (&lt;/=) 42 days prior to baseline&#xD;
&#xD;
          -  Compensated liver disease (Child-Pugh Class A clinical classification)&#xD;
&#xD;
          -  Either Liver biopsy performed within 2 years prior to baseline showing no or minimal&#xD;
             fibrosis (Liver Biopsy Scores and stable normal ALT levels (less than or equal to&#xD;
             upper limit of normal [ULN]) during the 6 months leading up to baseline (including two&#xD;
             separate occasions at least 1 month apart over the 6 months prior to baseline).&#xD;
             Screening ALT levels must be normal (&lt;/= ULN) OR Stable normal ALT levels (&lt;/= ULN),&#xD;
             during the 1 year leading up to baseline (including three separate occasions at least&#xD;
             1 month apart over the 1 year prior to baseline) and no signs of hepatocellular&#xD;
             carcinoma (HCC), advanced fibrosis/cirrhosis, or splenomegaly on liver abdominal&#xD;
             ultrasound at screening. Screening ALT levels must be normal (&lt;/= ULN)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants who have received investigational drugs or licensed treatments with anti&#xD;
             HBV activity (Exception: Participants who have had a limited [&lt;/= 7-day] course of&#xD;
             acyclovir for herpetic lesions more than 1 month before the study baseline visit are&#xD;
             not excluded)&#xD;
&#xD;
          -  Participants who have participated in any other clinical trial or who have received&#xD;
             any investigational drug within 6 months prior to baseline&#xD;
&#xD;
          -  Known hypersensitivity to interferon (IFN), pegylated interferon-alfa-2a or lamivudine&#xD;
             or entecavir&#xD;
&#xD;
          -  Positive test results at screening for hepatitis A virus Immunoglobulin M (IgM)&#xD;
             antibody (Ab), anti-hepatitis C virus (HCV) Ab, anti- hepatitis D (HDV) Ab or&#xD;
             anti-human immunodeficiency virus (HIV) Ab&#xD;
&#xD;
          -  Decompensated liver disease (e.g., Child-Pugh Class B or C clinical classification or&#xD;
             clinical evidence such as ascites or varices)&#xD;
&#xD;
          -  Advanced fibrosis or cirrhosis&#xD;
&#xD;
          -  Suspicion of HCC on liver abdominal ultrasound (all patients to have liver abdominal&#xD;
             ultrasound within 6 months prior to baseline)&#xD;
&#xD;
          -  History or other evidence of a medical condition associated with chronic liver disease&#xD;
             other than CHB including metabolic liver diseases such as hemochromatosis, Wilson's&#xD;
             disease or alpha-1 anti-trypsin deficiency&#xD;
&#xD;
          -  Active substance abuse within 6 months prior to screening&#xD;
&#xD;
          -  Sexually active females of childbearing potential and sexually active males who are&#xD;
             not willing to utilize reliable contraception during treatment and for 90 days&#xD;
             following the end of treatment&#xD;
&#xD;
          -  Females who are pregnant or who are breastfeeding (females of childbearing potential&#xD;
             who have a positive urine or serum pregnancy test result within 24 hours of baseline&#xD;
             are excluded)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Mercy Hosp Clinics</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032-3725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Womens and Childrens Hospital; Department of Gastroenterology</name>
      <address>
        <city>North Adelaide</city>
        <state>South Australia</state>
        <zip>5006</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires St-Luc</name>
      <address>
        <city>Bruxelles</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gent</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Essen; Klinik für Kinder- und Jugendmedizin Pädiatrie II</name>
      <address>
        <city>Essen</city>
        <zip>45122</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Zentrum für Kinder- und Jugendmedizin</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dr. von Haunerschen Kinderspital, Kinderchirurgische Klinik und Poliklinik</name>
      <address>
        <city>München</city>
        <zip>80337</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HELIOS Klinikum Wuppertal, Zentrum für Kinder- und Jugendmedizin, Universität Witten-Herdecke</name>
      <address>
        <city>Wuppertal</city>
        <zip>42283</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria Policlinico S. Orsola Malpighi; U.O. Malattie Infettive</name>
      <address>
        <city>Bologna</city>
        <state>Emilia-Romagna</state>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Malaya Medical Center; Department of Paediatrics</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>59100</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grigore Alexandrescu Emergency Clinical Hospital for Children</name>
      <address>
        <city>Bucharest</city>
        <zip>011743</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FSI Scientific research Institute of children's infections</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197022</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MC Gepatolog</name>
      <address>
        <city>Samara</city>
        <zip>443100</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chang-Gung Memorial Hospital-Linkou; Division of Pediatric Gastroenterology, Dept Pediatrics</name>
      <address>
        <city>Taoyuan County</city>
        <zip>333</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cukurova University Medical School Department of Pediatrics; Pediatric Infectious Diseases</name>
      <address>
        <city>Adana</city>
        <zip>01330</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ankara University School of Medicine, Pediatrics Department; Pediatric Gastroenterology</name>
      <address>
        <city>Ankara</city>
        <zip>06100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hacettepe Uni , School of Medicine; Gastroenterology</name>
      <address>
        <city>Ankara</city>
        <zip>06100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gazi Universitesi Tip Fakultesi Pediyatri Anabilim Dalı; Pediyatrik Gastroenteroloji</name>
      <address>
        <city>Ankara</city>
        <zip>06500</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SI Institute of the pediatrics, obstetrics and gynecology</name>
      <address>
        <city>Kyiv</city>
        <zip>04050</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Birmingham Children'S Hopsital; Liver Unit</name>
      <address>
        <city>Birmingham</city>
        <zip>B4 6NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leeds Teaching Hospitals NHS Trust</name>
      <address>
        <city>Leeds</city>
        <zip>LS9 7AU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kings College Hospital NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>SE5 9RS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Manchester General Hospital</name>
      <address>
        <city>Manchester</city>
        <zip>M8 5RB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Malaysia</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>Taiwan</country>
    <country>Turkey</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Brazil</country>
    <country>Dominican Republic</country>
    <country>Egypt</country>
    <country>Guatemala</country>
    <country>India</country>
    <country>Israel</country>
    <country>Korea, Republic of</country>
    <country>Singapore</country>
    <country>Thailand</country>
  </removed_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <results_first_submitted>July 15, 2020</results_first_submitted>
  <results_first_submitted_qc>August 21, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 24, 2020</results_first_posted>
  <last_update_submitted>August 21, 2020</last_update_submitted>
  <last_update_submitted_qc>August 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 24, 2020</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>
    <mesh_term>Hepatitis, Chronic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interferons</mesh_term>
    <mesh_term>Interferon-alpha</mesh_term>
    <mesh_term>Lamivudine</mesh_term>
    <mesh_term>Interferon alpha-2</mesh_term>
    <mesh_term>Peginterferon alfa-2a</mesh_term>
    <mesh_term>Entecavir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 26, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/79/NCT02263079/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study began as a single-site, three arm IST and was subsequently adapted as a multi-center, two arm study, conducted at 22 sites in Malaysia, Taiwan, Australia, Belgium, Germany, United Kingdom, Italy, Romania, Russian Federation, Turkey, Ukraine and the U.S. Enrolment was stopped prematurely, at which time 62 participants had been enrolled.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
          <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Untreated Control Participants</title>
          <description>Untreated control participants were observed up to 80 weeks.</description>
        </group>
        <group group_id="P3">
          <title>Peg-INF-Alfa-2A Monotherapy</title>
          <description>Participants received Peginterferon Alfa 2A subcutaneously once weekly with dosing based on body surface area (BSA) categories for 48 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="33"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="25"/>
                <participants group_id="P3" count="3">Completed study but not included in the analysis</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm to avoid participant re-identification as well as in consideration of any summary statistics would be misleading, therefore the three participants were presented in listings in the study report.</population>
      <group_list>
        <group group_id="B1">
          <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
          <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Untreated Control Participants</title>
          <description>Untreated control participants were observed up to 80 weeks.</description>
        </group>
        <group group_id="B3">
          <title>Peg-INF-Alfa-2A Monotherapy</title>
          <description>Participants received Peginterferon Alfa 2A subcutaneously once weekly with dosing based on body surface area (BSA) categories for 48 weeks.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="26"/>
            <count group_id="B2" value="33"/>
            <count group_id="B3" value="3"/>
            <count group_id="B4" value="62"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.</population>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="26"/>
                    <count group_id="B2" value="33"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="59"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11.9" spread="3.2"/>
                    <measurement group_id="B2" value="10.9" spread="3.7"/>
                    <measurement group_id="B4" value="11.3" spread="3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="26"/>
                    <count group_id="B2" value="33"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="59"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B4" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B4" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <population>Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="26"/>
                    <count group_id="B2" value="33"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="59"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B4" value="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <population>Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="26"/>
                    <count group_id="B2" value="33"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="59"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B4" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Multiple</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B4" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation</title>
        <description>This endpoint is defined as loss of HBsAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80). The percentage of responders (response rate) and 95% CI (using the Clopper-Pearson method) for the response rate are presented for each group.</description>
        <time_frame>24 weeks post-treatment/at the end of untreated observation (Week 80)</time_frame>
        <population>The Intent to treat (ITT) population was defined as all participants who received at least one dose of study medication of treated group. For untreated group, the ITT population included all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
            <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Untreated Control Participants</title>
            <description>Untreated control participants were observed up to 80 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation</title>
          <description>This endpoint is defined as loss of HBsAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80). The percentage of responders (response rate) and 95% CI (using the Clopper-Pearson method) for the response rate are presented for each group.</description>
          <population>The Intent to treat (ITT) population was defined as all participants who received at least one dose of study medication of treated group. For untreated group, the ITT population included all randomized participants.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" lower_limit="0.10" upper_limit="19.64"/>
                    <measurement group_id="O2" value="0" lower_limit="0.00" upper_limit="10.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Loss of HBsAg</title>
        <description>This endpoint is defined as loss of HBsAg at 1 year post-treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
        <time_frame>1 year post-end of treatment (End of treatment = Week 56)</time_frame>
        <population>The analysis population included participants from the Peg-INF-Alfa-2A arm, who received at least one dose of study medication of treated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated participants).</population>
        <group_list>
          <group group_id="O1">
            <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
            <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Loss of HBsAg</title>
          <description>This endpoint is defined as loss of HBsAg at 1 year post-treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
          <population>The analysis population included participants from the Peg-INF-Alfa-2A arm, who received at least one dose of study medication of treated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated participants).</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" lower_limit="0.10" upper_limit="19.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg)</title>
        <description>This endpoint is defined as loss of HBeAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
        <time_frame>24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)</time_frame>
        <population>All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)</population>
        <group_list>
          <group group_id="O1">
            <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
            <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Untreated Control Participants</title>
            <description>Untreated control participants were observed up to 80 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg)</title>
          <description>This endpoint is defined as loss of HBeAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
          <population>All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 Weeks post-treatment/Week 80</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" lower_limit="0.10" upper_limit="19.64"/>
                    <measurement group_id="O2" value="12.1" lower_limit="3.40" upper_limit="28.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 year post-end of treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.5" lower_limit="2.45" upper_limit="30.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs</title>
        <description>This endpoint measures the seroconversion to anti-HBs defined as loss of HBsAg and presence of anti-HBs at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
        <time_frame>24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)</time_frame>
        <population>All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)</population>
        <group_list>
          <group group_id="O1">
            <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
            <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Untreated Control Participants</title>
            <description>Untreated control participants were observed up to 80 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs</title>
          <description>This endpoint measures the seroconversion to anti-HBs defined as loss of HBsAg and presence of anti-HBs at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
          <population>All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 Weeks post-treatment/Week 80</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" lower_limit="0.10" upper_limit="19.64"/>
                    <measurement group_id="O2" value="0.0" lower_limit="0.00" upper_limit="10.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 year post-end of treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" lower_limit="0.10" upper_limit="19.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe</title>
        <description>This endpoint measures the seroconversion to anti-HBe defined as loss of HBeAg and presence of anti-HBe at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
        <time_frame>24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)</time_frame>
        <population>All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)</population>
        <group_list>
          <group group_id="O1">
            <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
            <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Untreated Control Participants</title>
            <description>Untreated control participants were observed up to 80 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe</title>
          <description>This endpoint measures the seroconversion to anti-HBe defined as loss of HBeAg and presence of anti-HBe at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
          <population>All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 Weeks post-treatment/Week 80</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="13.23"/>
                    <measurement group_id="O2" value="9.1" lower_limit="1.92" upper_limit="24.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 year post-end of treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7" lower_limit="0.95" upper_limit="25.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [&lt;] 20,000 International Units Per Milliliter [IU/mL], &lt; 2000 IU/mL, or Undetectable HBV DNA)</title>
        <description>This endpoint measures different HBV DNA levels (&lt;20000 IU/mL, &lt;2000 IU/mL and undetectable) measured by PCR or hybridization at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-treatment in the treated group. HBV-DNA undetectable is defined as &lt;29 IU/mL. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
        <time_frame>24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)</time_frame>
        <population>All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)</population>
        <group_list>
          <group group_id="O1">
            <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
            <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Untreated Control Participants</title>
            <description>Untreated control participants were observed up to 80 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [&lt;] 20,000 International Units Per Milliliter [IU/mL], &lt; 2000 IU/mL, or Undetectable HBV DNA)</title>
          <description>This endpoint measures different HBV DNA levels (&lt;20000 IU/mL, &lt;2000 IU/mL and undetectable) measured by PCR or hybridization at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-treatment in the treated group. HBV-DNA undetectable is defined as &lt;29 IU/mL. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
          <population>All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HBV-DNA &lt;20000 IU/mL at follow up Week 24/Week 80</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7" lower_limit="0.95" upper_limit="25.13"/>
                    <measurement group_id="O2" value="12.1" lower_limit="3.40" upper_limit="28.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HBV-DNA &lt;2000 IU/mL at follow up Week 24/Week 80</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7" lower_limit="0.95" upper_limit="25.13"/>
                    <measurement group_id="O2" value="12.1" lower_limit="3.40" upper_limit="28.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HBV-DNA Undetectable at follow up Week 24/Week 80</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="13.23"/>
                    <measurement group_id="O2" value="6.1" lower_limit="0.74" upper_limit="20.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HBV-DNA &lt;20000 IU/mL 1 year post-end of treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.4" lower_limit="4.36" upper_limit="34.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HBV-DNA &lt;2000 IU/mL 1 year post-end of treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7" lower_limit="0.95" upper_limit="25.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HBV-DNA Undetectable 1 year post-end of treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="13.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm</title>
        <description>This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Peg-INF-Alfa-2A + Lamivudine or Entecavir arm.</description>
        <time_frame>Baseline, Week 8, 20, 32, 44, 56, Follow up Week 4 and 24</time_frame>
        <population>The analysis population included participants from the Peg-INF-Alfa-2A arm, who received at least one dose of study medication of treated group. Only participants for whom data were collected are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
            <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm</title>
          <description>This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Peg-INF-Alfa-2A + Lamivudine or Entecavir arm.</description>
          <population>The analysis population included participants from the Peg-INF-Alfa-2A arm, who received at least one dose of study medication of treated group. Only participants for whom data were collected are included in the analysis.</population>
          <units>log10 IU/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.02" spread="0.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.74" spread="1.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.54" spread="0.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 32</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.56" spread="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 44</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.15" spread="0.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 56</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.21" spread="0.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fu Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.34" spread="2.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fu Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.31" spread="1.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in HBV DNA Levels in the Untreated Control Participants</title>
        <description>This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Untreated Control arm.</description>
        <time_frame>Baseline, Week 32, 56 and end of untreated observation (Week 80)</time_frame>
        <population>The analysis population included participants from the Untreated Control arm. Only participants for whom data were collected are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Untreated Control Participants</title>
            <description>Untreated control participants were observed up to 80 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in HBV DNA Levels in the Untreated Control Participants</title>
          <description>This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Untreated Control arm.</description>
          <population>The analysis population included participants from the Untreated Control arm. Only participants for whom data were collected are included in the analysis.</population>
          <units>log10 IU/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.22" spread="1.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 32</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.29" spread="0.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 56</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.57" spread="1.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 80</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.24" spread="2.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels &lt;20,000 IU/mL</title>
        <description>This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels &lt;20,000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
        <time_frame>24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)</time_frame>
        <population>All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)</population>
        <group_list>
          <group group_id="O1">
            <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
            <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Untreated Control Participants</title>
            <description>Untreated control participants were observed up to 80 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels &lt;20,000 IU/mL</title>
          <description>This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels &lt;20,000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
          <population>All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 Weeks post-treatment/Week 80</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="13.23"/>
                    <measurement group_id="O2" value="9.1" lower_limit="1.92" upper_limit="24.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 year post-end of treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7" lower_limit="0.95" upper_limit="25.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels &lt;2000 IU/mL</title>
        <description>This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels &lt;2000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
        <time_frame>24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)</time_frame>
        <population>All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)</population>
        <group_list>
          <group group_id="O1">
            <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
            <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Untreated Control Participants</title>
            <description>Untreated control participants were observed up to 80 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels &lt;2000 IU/mL</title>
          <description>This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels &lt;2000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.</description>
          <population>All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 Weeks post-treatment/Week 80</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="13.23"/>
                    <measurement group_id="O2" value="9.1" lower_limit="1.92" upper_limit="24.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 year post-end of treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7" lower_limit="0.95" upper_limit="25.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Adverse Events (AEs)</title>
        <description>An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
        <time_frame>Baseline up to 24 weeks post-treatment/end of untreated observation (Week 80)</time_frame>
        <population>The safety population included all participants who received at least one dose of study medication and had at least one post-baseline safety assessment. For untreated group, the safety population included all randomized participants who had at least one post-baseline safety assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
            <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Untreated Control Participants</title>
            <description>Untreated control participants were observed up to 80 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Adverse Events (AEs)</title>
          <description>An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
          <population>The safety population included all participants who received at least one dose of study medication and had at least one post-baseline safety assessment. For untreated group, the safety population included all randomized participants who had at least one post-baseline safety assessment.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>With at least one Non-Serious AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.3"/>
                    <measurement group_id="O2" value="45.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>With at least one Serious Adverse Event (SAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With AEs Leading to Dose Modification or Interruption</title>
        <description>This endpoint measures AEs and lab abnormalities leading to dose interruption or dose modification. Does modification included dose reduced, dose increased or drug interrupted. Adverse events included laboratory abnormalities reported as adverse events.</description>
        <time_frame>Baseline up to 24 weeks post-end of treatment</time_frame>
        <population>The safety analysis population included all participants who received at least one dose of study medication and had at least one post-baseline safety assessment in the Peg-INF-Alfa-2A treated arm.</population>
        <group_list>
          <group group_id="O1">
            <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
            <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With AEs Leading to Dose Modification or Interruption</title>
          <description>This endpoint measures AEs and lab abnormalities leading to dose interruption or dose modification. Does modification included dose reduced, dose increased or drug interrupted. Adverse events included laboratory abnormalities reported as adverse events.</description>
          <population>The safety analysis population included all participants who received at least one dose of study medication and had at least one post-baseline safety assessment in the Peg-INF-Alfa-2A treated arm.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum Concentration of Peg-INF-Alfa-2A</title>
        <description>The serum concentration of Peg-INF-Alfa-2A was measured in picogram/milliliter.</description>
        <time_frame>At Weeks 12, 16, 20, 32, 44, 56</time_frame>
        <population>The analysis population was the Peg-IFN-Alfa-2A + Lamivudine or Entecavir arm. The untreated arm did not receive any study medication. Only participants for whom data were collected are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
            <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Concentration of Peg-INF-Alfa-2A</title>
          <description>The serum concentration of Peg-INF-Alfa-2A was measured in picogram/milliliter.</description>
          <population>The analysis population was the Peg-IFN-Alfa-2A + Lamivudine or Entecavir arm. The untreated arm did not receive any study medication. Only participants for whom data were collected are included in the analysis.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 12 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8430" spread="6090"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16300" spread="10100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 20 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13800" spread="8740"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 32 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14900" spread="7710"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 32 24-48h Post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22700" spread="6070"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 32 72-96h Post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23000" spread="4900"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 32 168h Post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19300" spread="5880"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 44 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21900" spread="14200"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 56 Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25400" spread="13100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From Baseline up to 1 year post-end of treatment in the treated arm; From Baseline to end of untreated observation (Week 80) in the untreated group [up to clinical cut-off date 29 Jan 2020]</time_frame>
      <desc>The safety population included all participants who received at least one dose of study medication and had at least one post-baseline safety assessment. For untreated group, the safety population included all randomized participants who had at least one post-baseline safety assessment. Total # at Risk =0 in Other (Not Including Serious) Adverse Events section represents not reported data in consideration of participant re-identification.</desc>
      <group_list>
        <group group_id="E1">
          <title>Peg-IFN-Alfa-2A + Lamivudine or Entecavir</title>
          <description>Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Untreated Control Participants</title>
          <description>Untreated control participants were observed up to 80 weeks.</description>
        </group>
        <group group_id="E3">
          <title>Peg-INF-Alfa-2A Monotherapy</title>
          <description>Participants received Peginterferon Alfa 2A subcutaneously once weekly with dosing based on body surface area (BSA) categories for 48 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 22.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>PHARYNGITIS</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>DEHYDRATION</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 22.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="33"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL PAIN</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>ABDOMINAL PAIN UPPER</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>VOMITING</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>ASTHENIA</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>FATIGUE</sub_title>
                <counts group_id="E1" events="11" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>HYPERTHERMIA</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>INJECTION SITE BRUISING</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>PAIN</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>PYREXIA</sub_title>
                <counts group_id="E1" events="21" subjects_affected="11" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>GASTROENTERITIS</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>INFLUENZA</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>NASOPHARYNGITIS</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>CONTUSION</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>LIMB INJURY</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>DECREASED APPETITE</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>MYALGIA</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>PAIN IN EXTREMITY</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" events="91" subjects_affected="14" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>MIGRAINE</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>EPISTAXIS</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ACNE</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>ALOPECIA</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>ECZEMA</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>In accordance with the recommendation from the DSMB, enrollment was stopped due to low efficacy and a changed benefit risk assessment. Enrolled participants were allowed to complete treatment and were followed up for 1 year after the end of treatment</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Medical Communications</name_or_title>
      <organization>Hoffmann-La Roche</organization>
      <phone>800 821-8590</phone>
      <email>genentech@druginfo.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02263079
org study id: NV25361
secondary id: 2006-000977-31
nct id: NCT02263079
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This randomized, controlled, parallel group, open-label multicenter study will evaluate the
      efficacy and safety of a combination of pegylated interferon alfa-2A (Pegasys) plus
      lamivudine or entecavir compared with an untreated control group in participants with HBeAg
      positive CHB in the immune tolerant phase. NOTE: STUDY RECRUITMENT HAS BEEN TERMINATED
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation
time frame: 24 weeks post-treatment/at the end of untreated observation (Week 80)
description: This endpoint is defined as loss of HBsAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80). The percentage of responders (response rate) and 95% CI (using the Clopper-Pearson method) for the response rate are presented for each group.
measure: Percentage of Participants With Loss of HBsAg
time frame: 1 year post-end of treatment (End of treatment = Week 56)
description: This endpoint is defined as loss of HBsAg at 1 year post-treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
measure: Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg)
time frame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
description: This endpoint is defined as loss of HBeAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
measure: Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs
time frame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
description: This endpoint measures the seroconversion to anti-HBs defined as loss of HBsAg and presence of anti-HBs at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
measure: Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe
time frame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
description: This endpoint measures the seroconversion to anti-HBe defined as loss of HBeAg and presence of anti-HBe at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
measure: Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA)
time frame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
description: This endpoint measures different HBV DNA levels (<20000 IU/mL, <2000 IU/mL and undetectable) measured by PCR or hybridization at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-treatment in the treated group. HBV-DNA undetectable is defined as <29 IU/mL. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
measure: Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm
time frame: Baseline, Week 8, 20, 32, 44, 56, Follow up Week 4 and 24
description: This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Peg-INF-Alfa-2A + Lamivudine or Entecavir arm.
measure: Change From Baseline in HBV DNA Levels in the Untreated Control Participants
time frame: Baseline, Week 32, 56 and end of untreated observation (Week 80)
description: This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Untreated Control arm.
measure: Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <20,000 IU/mL
time frame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
description: This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels <20,000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
measure: Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <2000 IU/mL
time frame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
description: This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels <2000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
measure: Percentage of Participants With Adverse Events (AEs)
time frame: Baseline up to 24 weeks post-treatment/end of untreated observation (Week 80)
description: An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
measure: Percentage of Participants With AEs Leading to Dose Modification or Interruption
time frame: Baseline up to 24 weeks post-end of treatment
description: This endpoint measures AEs and lab abnormalities leading to dose interruption or dose modification. Does modification included dose reduced, dose increased or drug interrupted. Adverse events included laboratory abnormalities reported as adverse events.
measure: Serum Concentration of Peg-INF-Alfa-2A
time frame: At Weeks 12, 16, 20, 32, 44, 56
description: The serum concentration of Peg-INF-Alfa-2A was measured in picogram/milliliter.
arm group label: Peg-IFN-Alfa-2A + Lamivudine or Entecavir
arm group type: Experimental
description: Participants will receive lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.
arm group label: Untreated Control Participants
arm group type: No Intervention
description: Untreated control participants will be observed up to 80 weeks.
arm group label: Peg-INF-Alfa-2A Monotherapy
arm group type: Experimental
description: Participants will receive Peginterferon Alfa 2A subcutaneously once weekly with dosing based on body surface area (BSA) categories for 48 weeks.
intervention type: Drug
intervention name: Entecavir
description: Participants will receive entecavir, either as a film-coated tablet or oral solution, once daily at a dose of 0.015 milligrams per kilogram (mg/kg) (maximum daily dose of 0.5 mg).
arm group label: Peg-IFN-Alfa-2A + Lamivudine or Entecavir
intervention type: Drug
intervention name: Lamivudine
description: Participants will receive lamivudine, either as a film-coated tablet or oral solution, once daily at a dose of 3 mg/kg (maximum daily dose of 100 mg).
arm group label: Peg-IFN-Alfa-2A + Lamivudine or Entecavir
intervention type: Drug
intervention name: Pegylated Interferon Alfa-2A
description: Participants will receive pegylated interferon-alfa-2A at a body surface area (BSA) based dose of 180 micrograms per 1.73 square meter (mcg/1.73m^2) BSA.
arm group label: Peg-IFN-Alfa-2A + Lamivudine or Entecavir
arm group label: Peg-INF-Alfa-2A Monotherapy
other name: Pegasys, Peg-IFN-Alfa-2A
criteria: 
gender: All
minimum age: 3 Years
maximum age: 17 Years
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
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country: Australia
country: Belgium
country: Germany
country: Italy
country: Malaysia
country: Romania
country: Russian Federation
country: Taiwan
country: Turkey
country: Ukraine
country: United Kingdom
country: United States
country: Brazil
country: Dominican Republic
country: Egypt
country: Guatemala
country: India
country: Israel
country: Korea, Republic of
country: Singapore
country: Thailand
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: Interferons
mesh term: Interferon-alpha
mesh term: Lamivudine
mesh term: Interferon alpha-2
mesh term: Peginterferon alfa-2a
mesh term: Entecavir
sharing ipd: Yes
ipd description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: In accordance with the recommendation from the DSMB, enrollment was stopped due to low efficacy and a changed benefit risk assessment. Enrolled participants were allowed to complete treatment and were followed up for 1 year after the end of treatment
point of contact: 