<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/NCT01706575</url>
  </required_header>
  <id_info>
    <org_study_id>ML28262</org_study_id>
    <secondary_id>2012-000080-25</secondary_id>
    <nct_id>NCT01706575</nct_id>
  </id_info>
  <brief_title>A Study of Pegasys (Peginterferon Alfa-2a) Added to Nucleos(t)Ide Analogue Treatment in Participants With HBeAg-Negative Chronic Hepatitis B Genotype D Showing Stable Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Suppression</brief_title>
  <official_title>A Phase IIb, Open Label, Single Arm, Multicenter Study to Evaluate the Effect of 48-weeks PEG-Interferon Alfa-2a (PEG-IFN) Administration on Serum HBsAg in Chronic Hepatitis B, HBeAg-Negative, Genotype D Patients on Treatment With Nucleos(t)Ide Analogues (NAs), Showing Stable HBV DNA Suppression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <brief_summary>
    <textblock>
      This open-label, single-arm, multicenter study will evaluate the efficacy and safety of&#xD;
      adding Pegasys (peginterferon alfa-2a) to nucleos(t)ide analogue (NAs) treatment in&#xD;
      participants with HBeAg-negative chronic hepatitis B genotype D showing stable HBV DNA&#xD;
      suppression. After a 12-week Lead-in period on treatment with NA, participants with a HBsAg&#xD;
      decline &lt;0.5 log10 IU/ml will enter the Add-on period to receive Pegasys 180 mcg&#xD;
      subcutaneously weekly for 48 weeks in addition to their current NA treatment. Follow-up will&#xD;
      be a further 48 weeks, during which the participants will continue their NA treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">September 2013</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy: Percent Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at End of the Combination Treatment (Week 48)</measure>
    <time_frame>Baseline up to Week 48</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy: Percentage of Participants With Serum Hepatitis B Surface Antigen (HBsAg) Decrease &gt;/= 50% From Baseline at End of the Combination Treatment (Week 48)</measure>
    <time_frame>Baseline and Week 48</time_frame>
    <description>Participants who stopped pegylated interferon (PEG-IFN) treatment during the add-on phase due to serum HBsAg loss and HBsAg seroconversion were considered as responders.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96</measure>
    <time_frame>Baseline, Week 24, 72 and 96</time_frame>
    <description>Change is calculated by HBsAg titer at baseline - HBsAg titer at week of assessments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: Percentage of Participants With HBsAg Decrease &gt;/=1 log10 IU/ml From Baseline to Week 48</measure>
    <time_frame>Baseline, Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: Number of Participants With Serum HBsAg Loss at Week 12 That Persisted up to Week 96</measure>
    <time_frame>Week 12 up to Week 96</time_frame>
    <description>HBsAg loss is defined as HBsAg less than or equal to (&lt;/=) 0.05 IU/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: HBsAg Levels According to Interleukin 28B (IL28B) Genotypes</measure>
    <time_frame>Baseline and Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: HBsAg Levels According to Interferon-Inducible Protein 10 (IP-10) Serum Levels</measure>
    <time_frame>Baseline and Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety: Percentage of Participants With Adverse Events (AE)</measure>
    <time_frame>Baseline up to Week 48</time_frame>
    <description>An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">76</enrollment>
  <condition>Hepatitis B, Chronic</condition>
  <arm_group>
    <arm_group_label>Pegylated Interferon (Peginterferon) Alfa-2a</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than &lt;0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegylated Interferon (Peginterferon) Alfa-2a</intervention_name>
    <description>Peginterferon alfa-2a 180 mcg, subcutaneously (SC) once weekly for 48 weeks.</description>
    <arm_group_label>Pegylated Interferon (Peginterferon) Alfa-2a</arm_group_label>
    <other_name>Pegasys</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nucleos(t)ide Analogues (NA)</intervention_name>
    <description>Nucleos(t)ide analogues includes adefovir, entecavir, lamivudine or tenofovir.</description>
    <arm_group_label>Pegylated Interferon (Peginterferon) Alfa-2a</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult participants, 18 - 65 years of age&#xD;
&#xD;
          -  Chronic hepatitis B&#xD;
&#xD;
          -  Negative for HBeAg&#xD;
&#xD;
          -  On monotherapy with any nucleos(t)ide analogue (NA) but telbivudine at enrolment, and&#xD;
             HBV DNA persistently below 20 IU/ml for at least 12 months&#xD;
&#xD;
          -  HBsAg &gt;100 IU/ml at the beginning of the Lead-in phase, confirmed before addition of&#xD;
             Pegasys&#xD;
&#xD;
          -  Showing a steady HBsAg kinetic (HBsAg decrease &lt;0.5 log10 IU/ml from Week -12 to start&#xD;
             of the Add-on phase)&#xD;
&#xD;
          -  Negative pregnancy test for women of childbearing potential&#xD;
&#xD;
          -  Women of childbearing potential and fertile males with female partners of childbearing&#xD;
             potential must be using reliable contraception during and for 3 months after the&#xD;
             Add-on phase&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Coinfection with Hepatitis A virus (HAV), Hepatitis C virus (HCV), Hepatitis D virus&#xD;
             (HDV), Human Immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Evidence of decompensated liver disease (Child-Pugh &gt;/=6)&#xD;
&#xD;
          -  History or other evidence of a medical condition associated with chronic liver disease&#xD;
             (e.g. hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposure)&#xD;
&#xD;
          -  Known hypersensitivity to peginterferon alfa-2a&#xD;
&#xD;
          -  Pregnant of breastfeeding women&#xD;
&#xD;
          -  Evidence of alcohol and/or drug abuse&#xD;
&#xD;
          -  History of severe psychiatric disease, especially depression&#xD;
&#xD;
          -  History of immunologically mediated disease&#xD;
&#xD;
          -  History or evidence of bleeding from esophageal varices or other conditions consistent&#xD;
             with decompensated liver disease&#xD;
&#xD;
          -  History or evidence of severe pulmonary disease associated with functional limitations&#xD;
&#xD;
          -  History of severe cardiac disease&#xD;
&#xD;
          -  History of severe seizure disorder or current anticonvulsant use&#xD;
&#xD;
          -  Evidence of an active or suspected cancer or a history of malignancy (other than&#xD;
             basocellular carcinoma or in situ cervical carcinoma) within 5 years prior to study&#xD;
             entry&#xD;
&#xD;
          -  History of having received any systemic anti-neoplastic (including radiation) or&#xD;
             immunomodulatory (including systemic corticosteroids) treatment &lt;/= 6 months prior to&#xD;
             the first dose or the expectation that such a treatment will be needed at any time&#xD;
             during the study&#xD;
&#xD;
          -  History or other evidence of severe retinopathy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nuovo Policlinico; Dipartimento di Malattie Infettive</name>
      <address>
        <city>Napoli</city>
        <state>Campania</state>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Napoli</city>
        <state>Campania</state>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNI DEGLI STUDI - POLICLINICA S. ORSOLA; Dipartimento Malattie dell'Apparato Digerente e Medicina In</name>
      <address>
        <city>Bologna</city>
        <state>Emilia-Romagna</state>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bologna</city>
        <state>Emilia-Romagna</state>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Medica</name>
      <address>
        <city>Udine</city>
        <state>Friuli-Venezia Giulia</state>
        <zip>33100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Udine</city>
        <state>Friuli-Venezia Giulia</state>
        <zip>33100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Umberto I Di Roma</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>D.I,M.I.; Cattedra Di Gastroenterologia</name>
      <address>
        <city>Genova</city>
        <state>Liguria</state>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Genova</city>
        <state>Liguria</state>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Gastroenterologia</name>
      <address>
        <city>Torino</city>
        <state>Piemonte</state>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Torino</city>
        <state>Piemonte</state>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Universitaria Ospedali Riuniti Di Foggia; Malattie Infettive</name>
      <address>
        <city>Foggia</city>
        <state>Puglia</state>
        <zip>71100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Foggia</city>
        <state>Puglia</state>
        <zip>71100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Universitaria Policlinico Monserrato Di Cagliari; Gastroenterologia</name>
      <address>
        <city>Cagliari</city>
        <state>Sardegna</state>
        <zip>09042</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uni Di Cagliari; Dept. Di Scienze Mediche</name>
      <address>
        <city>Cagliari</city>
        <state>Sardegna</state>
        <zip>09042</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cagliari</city>
        <state>Sardegna</state>
        <zip>09042</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Az. Osp. Uni. Ria Policlinico G. Martino; Dept. Di Med. Interna E Terapia Medica - Ii Clinica Medica</name>
      <address>
        <city>Messina</city>
        <state>Sicilia</state>
        <zip>98124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Messina</city>
        <state>Sicilia</state>
        <zip>98124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Di Clinica Medica 1 A; Divisione Di Medicina Generale E Gastroenterologia</name>
      <address>
        <city>Palermo</city>
        <state>Sicilia</state>
        <zip>90127</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Palermo</city>
        <state>Sicilia</state>
        <zip>90127</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Cisanello - Az. Osp. Pisana; Unità Operativa Di Gastroenterologia Ed Epatologia</name>
      <address>
        <city>Pisa</city>
        <state>Toscana</state>
        <zip>56124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pisa</city>
        <state>Toscana</state>
        <zip>56124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Padova</city>
        <state>Veneto</state>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>October 10, 2012</study_first_submitted>
  <study_first_submitted_qc>October 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2012</study_first_posted>
  <results_first_submitted>June 24, 2016</results_first_submitted>
  <results_first_submitted_qc>June 24, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 5, 2016</results_first_posted>
  <last_update_submitted>December 29, 2016</last_update_submitted>
  <last_update_submitted_qc>December 29, 2016</last_update_submitted_qc>
  <last_update_posted type="Actual">February 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis B, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interferons</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A total of 76 participants started the study and were included in lead-in period. Out of 76 participants, 70 received study drug.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Pegylated Interferon (Peginterferon) Alfa-2a</title>
          <description>Participants receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than &lt;0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="76"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="70"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="64"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Participant Withdrew Consent</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Started but not Treated</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Lead-in participants included all participants enrolled in lead-in period.</population>
      <group_list>
        <group group_id="B1">
          <title>Pegylated Interferon (Peginterferon) Alfa-2a</title>
          <description>Participants receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than &lt;0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="76"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49.82" spread="8.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Efficacy: Percent Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at End of the Combination Treatment (Week 48)</title>
        <time_frame>Baseline up to Week 48</time_frame>
        <population>Per-Protocol Population (PP) included all participants without severe protocol violations, including major inclusion or exclusion criteria violations.</population>
        <group_list>
          <group group_id="O1">
            <title>Pegylated Interferon (Peginterferon) Alfa-2a</title>
            <description>Participants receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than &lt;0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy: Percent Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at End of the Combination Treatment (Week 48)</title>
          <population>Per-Protocol Population (PP) included all participants without severe protocol violations, including major inclusion or exclusion criteria violations.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.13" spread="32.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Efficacy: Percentage of Participants With Serum Hepatitis B Surface Antigen (HBsAg) Decrease &gt;/= 50% From Baseline at End of the Combination Treatment (Week 48)</title>
        <description>Participants who stopped pegylated interferon (PEG-IFN) treatment during the add-on phase due to serum HBsAg loss and HBsAg seroconversion were considered as responders.</description>
        <time_frame>Baseline and Week 48</time_frame>
        <population>PP included all participants without severe protocol violations, including major inclusion or exclusion criteria violations and who were undergoing the Week 48 visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Pegylated Interferon (Peginterferon) Alfa-2a</title>
            <description>Participants receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than &lt;0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy: Percentage of Participants With Serum Hepatitis B Surface Antigen (HBsAg) Decrease &gt;/= 50% From Baseline at End of the Combination Treatment (Week 48)</title>
          <description>Participants who stopped pegylated interferon (PEG-IFN) treatment during the add-on phase due to serum HBsAg loss and HBsAg seroconversion were considered as responders.</description>
          <population>PP included all participants without severe protocol violations, including major inclusion or exclusion criteria violations and who were undergoing the Week 48 visit.</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="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96</title>
        <description>Change is calculated by HBsAg titer at baseline - HBsAg titer at week of assessments.</description>
        <time_frame>Baseline, Week 24, 72 and 96</time_frame>
        <population>PP included all participants without severe protocol violations, including major inclusion or exclusion criteria violations. Here, number of participants analyzed signifies those participants who were evaluable for the outcome measure and n signifies the number of participants who were evaluated at specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Pegylated Interferon (Peginterferon) Alfa-2a</title>
            <description>Participants receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than &lt;0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96</title>
          <description>Change is calculated by HBsAg titer at baseline - HBsAg titer at week of assessments.</description>
          <population>PP included all participants without severe protocol violations, including major inclusion or exclusion criteria violations. Here, number of participants analyzed signifies those participants who were evaluable for the outcome measure and n signifies the number of participants who were evaluated at specified time points.</population>
          <units>international units per millilitre</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n= 56)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 24 (n= 56)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-546.32" spread="1215.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 72 (n= 55)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-815.69" spread="1394.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 96 (n= 55)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-728.16" spread="1418.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy: Percentage of Participants With HBsAg Decrease &gt;/=1 log10 IU/ml From Baseline to Week 48</title>
        <time_frame>Baseline, Week 48</time_frame>
        <population>PP included all participants without severe protocol violations, including major inclusion or exclusion criteria violations and who were undergoing the Week 48 visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Pegylated Interferon (Peginterferon) Alfa-2a</title>
            <description>Participants receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than &lt;0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy: Percentage of Participants With HBsAg Decrease &gt;/=1 log10 IU/ml From Baseline to Week 48</title>
          <population>PP included all participants without severe protocol violations, including major inclusion or exclusion criteria violations and who were undergoing the Week 48 visit.</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="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy: Number of Participants With Serum HBsAg Loss at Week 12 That Persisted up to Week 96</title>
        <description>HBsAg loss is defined as HBsAg less than or equal to (&lt;/=) 0.05 IU/ml.</description>
        <time_frame>Week 12 up to Week 96</time_frame>
        <population>PP included all participants without severe protocol violations, including major inclusion or exclusion criteria violations.</population>
        <group_list>
          <group group_id="O1">
            <title>Pegylated Interferon (Peginterferon) Alfa-2a</title>
            <description>Participants receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than &lt;0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy: Number of Participants With Serum HBsAg Loss at Week 12 That Persisted up to Week 96</title>
          <description>HBsAg loss is defined as HBsAg less than or equal to (&lt;/=) 0.05 IU/ml.</description>
          <population>PP included all participants without severe protocol violations, including major inclusion or exclusion criteria violations.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy: HBsAg Levels According to Interleukin 28B (IL28B) Genotypes</title>
        <time_frame>Baseline and Week 48</time_frame>
        <population>Data were not collected, and the outcome measure was not analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Pegylated Interferon (Peginterferon) Alfa-2a</title>
            <description>Participants receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than &lt;0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy: HBsAg Levels According to Interleukin 28B (IL28B) Genotypes</title>
          <population>Data were not collected, and the outcome measure was not analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy: HBsAg Levels According to Interferon-Inducible Protein 10 (IP-10) Serum Levels</title>
        <time_frame>Baseline and Week 48</time_frame>
        <population>Data were not collected, and the outcome measure was not analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Pegylated Interferon (Peginterferon) Alfa-2a</title>
            <description>Participants receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than &lt;0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy: HBsAg Levels According to Interferon-Inducible Protein 10 (IP-10) Serum Levels</title>
          <population>Data were not collected, and the outcome measure was not analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety: Percentage of Participants With Adverse Events (AE)</title>
        <description>An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.</description>
        <time_frame>Baseline up to Week 48</time_frame>
        <population>Safety population included all participants who received least one dose of the study drug and had at least one post-dose safety assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pegylated Interferon (Peginterferon) Alfa-2a</title>
            <description>Participants receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than &lt;0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety: Percentage of Participants With Adverse Events (AE)</title>
          <description>An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.</description>
          <population>Safety population included all participants who received least one dose of the study drug and had at least one post-dose 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="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to Week 48</time_frame>
      <desc>Safety Population: Safety population included all participants who received least one dose of the study drug and had at least one post-dose safety assessment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Pegylated Interferon (Peginterferon) Alfa-2a</title>
          <description>Participants receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than &lt;0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (17.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Papillary thyroid cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Squamous cell carcinoma of skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (17.1)</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="56" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="69"/>
              </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>
    <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/NCT01706575
org study id: ML28262
secondary id: 2012-000080-25
nct id: NCT01706575
lead sponsor: 
This open-label, single-arm, multicenter study will evaluate the efficacy and safety of
      adding Pegasys (peginterferon alfa-2a) to nucleos(t)ide analogue (NAs) treatment in
      participants with HBeAg-negative chronic hepatitis B genotype D showing stable HBV DNA
      suppression. After a 12-week Lead-in period on treatment with NA, participants with a HBsAg
      decline <0.5 log10 IU/ml will enter the Add-on period to receive Pegasys 180 mcg
      subcutaneously weekly for 48 weeks in addition to their current NA treatment. Follow-up will
      be a further 48 weeks, during which the participants will continue their NA treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Efficacy: Percent Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at End of the Combination Treatment (Week 48)
time frame: Baseline up to Week 48
measure: Efficacy: Percentage of Participants With Serum Hepatitis B Surface Antigen (HBsAg) Decrease >/= 50% From Baseline at End of the Combination Treatment (Week 48)
time frame: Baseline and Week 48
description: Participants who stopped pegylated interferon (PEG-IFN) treatment during the add-on phase due to serum HBsAg loss and HBsAg seroconversion were considered as responders.
measure: Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96
time frame: Baseline, Week 24, 72 and 96
description: Change is calculated by HBsAg titer at baseline - HBsAg titer at week of assessments.
measure: Efficacy: Percentage of Participants With HBsAg Decrease >/=1 log10 IU/ml From Baseline to Week 48
time frame: Baseline, Week 48
measure: Efficacy: Number of Participants With Serum HBsAg Loss at Week 12 That Persisted up to Week 96
time frame: Week 12 up to Week 96
description: HBsAg loss is defined as HBsAg less than or equal to (</=) 0.05 IU/ml.
measure: Efficacy: HBsAg Levels According to Interleukin 28B (IL28B) Genotypes
time frame: Baseline and Week 48
measure: Efficacy: HBsAg Levels According to Interferon-Inducible Protein 10 (IP-10) Serum Levels
time frame: Baseline and Week 48
measure: Safety: Percentage of Participants With Adverse Events (AE)
time frame: Baseline up to Week 48
description: An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
arm group label: Pegylated Interferon (Peginterferon) Alfa-2a
arm group type: Experimental
description: Participants receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than <0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy.
intervention type: Drug
intervention name: Pegylated Interferon (Peginterferon) Alfa-2a
description: Peginterferon alfa-2a 180 mcg, subcutaneously (SC) once weekly for 48 weeks.
arm group label: Pegylated Interferon (Peginterferon) Alfa-2a
other name: Pegasys
intervention type: Drug
intervention name: Nucleos(t)ide Analogues (NA)
description: Nucleos(t)ide analogues includes adefovir, entecavir, lamivudine or tenofovir.
arm group label: Pegylated Interferon (Peginterferon) Alfa-2a
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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facility: 
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Interferons
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 