<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/NCT03235154</url>
  </required_header>
  <id_info>
    <org_study_id>15-05</org_study_id>
    <nct_id>NCT03235154</nct_id>
  </id_info>
  <brief_title>A Pilot Study of Treating HCV at a Psychiatrist-staffed Outpatient Addiction Clinic</brief_title>
  <official_title>Bridging Care to HCV Treatment Among Opiate Dependent Patients on Buprenorphine/Naloxone Maintenance Therapy: A Pilot Study of Treating HCV With Epclusa at a Psychiatrist-staffed Outpatient Addiction Clinic</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Community Research Initiative of New England</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Community Research Initiative of New England</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this pilot study is to investigate the safety, effectiveness and&#xD;
      tolerability of the study medication in the treatment of people with chronic hepatitis C&#xD;
      virus infection who regularly attend a psychiatrist-staffed clinic for opiate addiction&#xD;
      treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An estimated 3.2 million people in the United States are currently infected with hepatitis C&#xD;
      virus (HCV). Since 1990, when the US introduced screening of the blood supply for HCV,&#xD;
      injection drug use has been the primary mode of HCV transmission in the United States. It is&#xD;
      widely recognized that addressing the HCV epidemic among people who inject drugs (PWID)&#xD;
      depends on increasing access to: 1) clean injection equipment; 2) opiate substitution therapy&#xD;
      (OST); 3) curative HCV treatment; and 4) assistance with comorbid psychiatric conditions and&#xD;
      social issues (Robaeys, C et al, 2013).&#xD;
&#xD;
      Nevertheless, access to HCV treatment among current and former injection drug users is&#xD;
      thought to be limited by several factors including: 1) insufficient number of infectious&#xD;
      disease and gastroenterology providers and 2) provider and third-party payor concerns about&#xD;
      adherence to medication and the risk of reinfection (Aspinall, EJ et al, 2013). Strategies to&#xD;
      increase access among current and former injection drug users to direct acting antiviral&#xD;
      drugs are urgently needed. The purpose of the current study is to assess the impact of&#xD;
      co-treating chronic hepatitis C infection and opiate dependence within the context of an&#xD;
      outpatient addiction clinic staffed by psychiatrists. The beneficial impact of co-treating&#xD;
      opiate dependence and an infectious illness has been demonstrated in the case of HIV&#xD;
      infection. Altice and colleagues conducted an observational study of HIV-infected&#xD;
      opiate-dependent patients who were offered OST with buprenorphine/naloxone at 10 different&#xD;
      HIV clinics. Subjects initiating buprenorphine/naloxone were more likely to initiate or&#xD;
      remain on ART (antiretroviral therapy) (Altice, 2011).&#xD;
&#xD;
      The Extension for Community Healthcare Outcomes (ECHO) program has demonstrated that with&#xD;
      proper training and mentorship, primary care providers with no prior experience in managing&#xD;
      HCV are able to treat the disease effectively (Arora et al, 2011). Since the publication of&#xD;
      the ECHO study, the treatment of HCV has become considerably less complicated due to the&#xD;
      widespread availability of safe, highly effective single tablet regimens, such as Epclusa.&#xD;
      The investigators believe that treatment of HCV is now well within the grasp of physicians&#xD;
      and other healthcare providers without training in internal or family medicine.&#xD;
&#xD;
      This single arm pilot study will assess HCV treatment with Epclusa at an outpatient addiction&#xD;
      clinic staffed by psychiatrists. The investigators hypothesize that with proper training and&#xD;
      mentorship, psychiatrists who are also a licensed buprenorphine/naloxone providers will be&#xD;
      able to effectively assess liver health and treat chronic hepatitis C infection with Epclusa.&#xD;
      Further, the investigators hypothesize that patients with chronic hepatitis C infection on&#xD;
      buprenorphine/naloxone maintenance therapy who are treated for HCV by a psychiatrist during&#xD;
      regularly scheduled visits to an addiction clinic will have high rates of adherence to HCV&#xD;
      treatment and achieve SVR12 (sustained virologic response, 12 weeks post-treatment).&#xD;
&#xD;
      Given that subjects will receive standard of care evaluation and treatment for their chronic&#xD;
      hepatitis C infection, the investigators believe that study participation poses minimal risk.&#xD;
      Indeed, The investigators believe that subjects will benefit from improved access to this&#xD;
      important treatment which will be provided at a convenient location by a known physician&#xD;
      under the guidance of an infectious disease physician with extensive experience treating HCV&#xD;
      infection.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 11, 2017</start_date>
  <completion_date type="Actual">September 26, 2019</completion_date>
  <primary_completion_date type="Actual">September 26, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Sustained Virologic Response at 12 Weeks Post Treatment (SVR-12)</measure>
    <time_frame>This outcome measure will be assessed for each participant 12 weeks after completion of a 12 week course of treatment</time_frame>
    <description>To assess the effectiveness of HCV treatment with velpatasvir/sofosbuvir administered by psychiatrist/licensed buprenorphine/naloxone providers during regularly scheduled visits to an outpatient addiction clinic for buprenorphine/naloxone replacement therapy and mental healthcare, as measured by percentage of patients achieving SVR-12 (defined as HCV RNA &lt; lower limit of quantification (LLOQ) 12 weeks after discontinuation of study treatment),</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life</measure>
    <time_frame>Baseline and 12 weeks post treatment</time_frame>
    <description>Change in mean score on 5-point LIkert Scale to statement &quot;My Health is Excellent&quot; (1=definitely true, 5=definitely false) from baseline and 12 weeks post-treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence to Study Treatment</measure>
    <time_frame>This outcome measure will be assessed for each participant during a 12 week course of study treatment.</time_frame>
    <description>To assess adherence to velpatasvir/sofosbuvir therapy among participants administered treatment in the context of visits to an outpatient addiction clinic for buprenorphine/naloxone replacement therapy and mental health care.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Hepatitis C, Chronic</condition>
  <condition>Hepatitis C</condition>
  <condition>Opiate Dependence</condition>
  <arm_group>
    <arm_group_label>Treatment Arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>In this open label, single arm study, all subjects will receive the intervention as prescribed by psychiatrists in the office based opiate addition treatment program.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sofosbuvir/velpatasvir</intervention_name>
    <description>12 week treatment with once daily sofosbuvir/velpatasvir fixed dose combination therapy. Tablets are formulated with 400mg sofosbuvir and 100mg velpatasvir in pink, diamond-shaped, film coated tablets.</description>
    <arm_group_label>Treatment Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Willing and able to provide written informed consent&#xD;
&#xD;
          2. Age ≥ 18 years&#xD;
&#xD;
          3. Confirmation of chronic HCV infection as documented by a positive HCV antibody test at&#xD;
             least 6 months prior to the Baseline/Day 1 visit and positive HCV RNA test at&#xD;
             screening&#xD;
&#xD;
          4. HCV genotype 1, 2, 3, 4, 5 or 6&#xD;
&#xD;
          5. In stable remission from opiate use on buprenorphine/naloxone for at least 12 weeks&#xD;
&#xD;
          6. Within the following laboratory parameters as assessed at the screening visit:&#xD;
&#xD;
               1. HCV RNA quantifiable&#xD;
&#xD;
               2. Screening rhythm strip without bradycardia (heart rate &gt; 60 or, if on beta&#xD;
                  blocker, &gt; 55 BPM)&#xD;
&#xD;
               3. Alanine Aminotransferase (ALT) ≤ 10 x ULN (upper limit of normal)&#xD;
&#xD;
               4. Aspartate Aminotransferase (AST) ≤ 10 x ULN&#xD;
&#xD;
               5. Direct bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
               6. Platelets &gt; 60,000&#xD;
&#xD;
               7. Hemoglobin A1C (HbA1c) ≤ 10%&#xD;
&#xD;
               8. Creatinine clearance ≥ 30 mL/min, as calculated by the Cockcroft-Gault equation&#xD;
&#xD;
               9. Albumin ≥ 3g/dL&#xD;
&#xD;
              10. International Normalized Ratio (INR) ≤ 1.5 x ULN or on an anticoagulant regimen&#xD;
                  affecting INR&#xD;
&#xD;
          7. Female subject is eligible to enter if it is confirmed that she is:&#xD;
&#xD;
               1. Not pregnant or nursing&#xD;
&#xD;
               2. Not of childbearing potential (i.e. s/p hysterectomy, oophorectomy or has&#xD;
                  medically documented ovarian failure, or are postmenopausal women &gt; 50 years of&#xD;
                  age with cessation of menses for 12 months or greater) OR Of childbearing&#xD;
                  potential with a negative serum pregnancy test within 2 weeks of screening, a&#xD;
                  negative urine pregnancy test on Day 1, and a commitment to either abstain from&#xD;
                  intercourse or consistently use an acceptable method of birth control (Appendix&#xD;
                  4) in addition to condom use by her male partner(s) from the date of screening&#xD;
                  until 30 days after the last dose of study drug&#xD;
&#xD;
          8. All male study participants must agree to consistently and correctly use condoms with&#xD;
             their female partner(s) and their female partner(s) must agree to use an acceptable&#xD;
             method of birth control (listed) from the date of screening until 90 days after the&#xD;
             last dose of study drug&#xD;
&#xD;
          9. Male subjects must refrain from sperm donation from the date of screening until 90&#xD;
             days after the last dose of study drug&#xD;
&#xD;
         10. Subject must be in generally good health, with the exception of HCV, in the opinion of&#xD;
             the Sponsor-Investigator or Sub-Investigator(s)&#xD;
&#xD;
         11. Subject must be able to comply with dosing instructions for study drug administration&#xD;
             and able to complete the study visits, including all required post-treatment visits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of decompensated cirrhosis as defined by encephalopathy, ascites, or a&#xD;
             history of a variceal bleed&#xD;
&#xD;
          2. Prior treatment with direct acting antiviral hepatitis C medications&#xD;
&#xD;
          3. Positive urine drug toxicity test at screening (except for cannabinoids and prescribed&#xD;
             medications)&#xD;
&#xD;
          4. Absence of buprenorphine in urine sample at screening&#xD;
&#xD;
          5. Currently pregnant or breastfeeding female&#xD;
&#xD;
          6. Detectable HIV RNA &gt; 50 copies/ml (co-infected subjects with suppressed viral load are&#xD;
             eligible for participation)&#xD;
&#xD;
          7. Use of any prohibited concomitant medication within 28 days prior to day 1&#xD;
&#xD;
          8. Chronic use of systemically administered immunosuppressive agents&#xD;
&#xD;
          9. Difficulty with blood collection or poor venous access&#xD;
&#xD;
         10. History of solid organ transplantation&#xD;
&#xD;
         11. Known significant allergy to sofosbuvir or velpatasvir&#xD;
&#xD;
         12. Current chronic liver disease of a non-HCV etiology (including hemochromatosis,&#xD;
             Wilson's disease, alfa-1 antitrypsin deficiency)&#xD;
&#xD;
         13. Active Hepatitis B virus (HBV) infection defined as either a positive HBV surface&#xD;
             antigen test or a positive test for HBV DNA. (Subjects who are positive for HBV core&#xD;
             antibody but negative for Hepatitis B surface antibody, surface antigen, and DNA ARE&#xD;
             eligible)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Amy E Colson, MD MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Community Research Initiative of New England</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cambridge Health Alliance Outpatient Addiction Services</name>
      <address>
        <city>Somerville</city>
        <state>Massachusetts</state>
        <zip>02143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Altice FL, Bruce RD, Lucas GM, Lum PJ, Korthuis PT, Flanigan TP, Cunningham CO, Sullivan LE, Vergara-Rodriguez P, Fiellin DA, Cajina A, Botsko M, Nandi V, Gourevitch MN, Finkelstein R; BHIVES Collaborative. HIV treatment outcomes among HIV-infected, opioid-dependent patients receiving buprenorphine/naloxone treatment within HIV clinical care settings: results from a multisite study. J Acquir Immune Defic Syndr. 2011 Mar 1;56 Suppl 1(Suppl 1):S22-32. doi: 10.1097/QAI.0b013e318209751e.</citation>
    <PMID>21317590</PMID>
  </reference>
  <reference>
    <citation>Arora S, Thornton K, Murata G, Deming P, Kalishman S, Dion D, Parish B, Burke T, Pak W, Dunkelberg J, Kistin M, Brown J, Jenkusky S, Komaromy M, Qualls C. Outcomes of treatment for hepatitis C virus infection by primary care providers. N Engl J Med. 2011 Jun 9;364(23):2199-207. doi: 10.1056/NEJMoa1009370. Epub 2011 Jun 1.</citation>
    <PMID>21631316</PMID>
  </reference>
  <reference>
    <citation>Robaeys G, Grebely J, Mauss S, Bruggmann P, Moussalli J, De Gottardi A, Swan T, Arain A, Kautz A, Stover H, Wedemeyer H, Schaefer M, Taylor L, Backmund M, Dalgard O, Prins M, Dore GJ; International Network on Hepatitis in Substance Users. Recommendations for the management of hepatitis C virus infection among people who inject drugs. Clin Infect Dis. 2013 Aug;57 Suppl 2:S129-37. doi: 10.1093/cid/cit302.</citation>
    <PMID>23884061</PMID>
  </reference>
  <reference>
    <citation>Aspinall EJ, Corson S, Doyle JS, Grebely J, Hutchinson SJ, Dore GJ, Goldberg DJ, Hellard ME. Treatment of hepatitis C virus infection among people who are actively injecting drugs: a systematic review and meta-analysis. Clin Infect Dis. 2013 Aug;57 Suppl 2:S80-9. doi: 10.1093/cid/cit306.</citation>
    <PMID>23884071</PMID>
  </reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>July 27, 2017</study_first_submitted>
  <study_first_submitted_qc>July 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 1, 2017</study_first_posted>
  <results_first_submitted>September 22, 2020</results_first_submitted>
  <results_first_submitted_qc>April 22, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 13, 2021</results_first_posted>
  <last_update_submitted>April 22, 2021</last_update_submitted>
  <last_update_submitted_qc>April 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HCV</keyword>
  <keyword>Suboxone</keyword>
  <keyword>Epclusa</keyword>
  <keyword>psychiatrist</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis C, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Opioid-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sofosbuvir</mesh_term>
    <mesh_term>Velpatasvir</mesh_term>
    <mesh_term>Sofosbuvir-velpatasvir drug combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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>September 13, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/54/NCT03235154/Prot_SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form: ICF for patients</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 3, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/54/NCT03235154/ICF_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form: ICF for providers</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 5, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/54/NCT03235154/ICF_003.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment Arm</title>
          <description>In this open label, single arm study, all subjects will receive the intervention as prescribed by psychiatrists in the office based opiate addition treatment program.&#xD;
sofosbuvir/velpatasvir: 12 week treatment with once daily sofosbuvir/velpatasvir fixed dose combination therapy. Tablets are formulated with 400mg sofosbuvir and 100mg velpatasvir in pink, diamond-shaped, film coated tablets.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed Epclusa. Treatment</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>12-wk Post-treatment HCV RNA Measured</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </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_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Single Arm Intervention</title>
          <description>12-week Epclusa Treatment</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="11"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="48" lower_limit="25" upper_limit="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</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="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Co-morbid axis 1 diagnosis present</title>
          <description>The presence of a co-morbid axis 1 diagnosis was confirmed by the treating psychiatrist. Axis 1 diagnoses refer to major mental disorders including mood disorders, anxiety disorders and schizophrenia/psychotic disorders</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HCV (hepatitis C virus) RNA</title>
          <units>IU/ml</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2,662,207" lower_limit="29384" upper_limit="10408895"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline FibroSure fibrosis stage</title>
          <description>The level of liver fibrosis was determined by the FibroSure HCV blood test which uses a combination of six serum markers plus age and gender in a patented algorithm to generate a measure of fibrosis. The stages of fibrosis range from 0 (no fibrosis) to 4 (liver cirrhosis). Stage F1 refers to portal fibrosis, stage F2 to bridging fibrosis with few septa, and stage F3 to bridging fibrosis with many septa.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>F0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>F1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>F2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>F3</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>F4</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Sustained Virologic Response at 12 Weeks Post Treatment (SVR-12)</title>
        <description>To assess the effectiveness of HCV treatment with velpatasvir/sofosbuvir administered by psychiatrist/licensed buprenorphine/naloxone providers during regularly scheduled visits to an outpatient addiction clinic for buprenorphine/naloxone replacement therapy and mental healthcare, as measured by percentage of patients achieving SVR-12 (defined as HCV RNA &lt; lower limit of quantification (LLOQ) 12 weeks after discontinuation of study treatment),</description>
        <time_frame>This outcome measure will be assessed for each participant 12 weeks after completion of a 12 week course of treatment</time_frame>
        <population>subjects who completed Epclusa treatment and had HCV RNA measured 12 weeks after completion of treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment Arm</title>
            <description>In this open label, single arm study, all subjects will receive the intervention as prescribed by psychiatrists in the office based opiate addition treatment program.&#xD;
sofosbuvir/velpatasvir: 12 week treatment with once daily sofosbuvir/velpatasvir fixed dose combination therapy. Tablets are formulated with 400mg sofosbuvir and 100mg velpatasvir in pink, diamond-shaped, film coated tablets.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Sustained Virologic Response at 12 Weeks Post Treatment (SVR-12)</title>
          <description>To assess the effectiveness of HCV treatment with velpatasvir/sofosbuvir administered by psychiatrist/licensed buprenorphine/naloxone providers during regularly scheduled visits to an outpatient addiction clinic for buprenorphine/naloxone replacement therapy and mental healthcare, as measured by percentage of patients achieving SVR-12 (defined as HCV RNA &lt; lower limit of quantification (LLOQ) 12 weeks after discontinuation of study treatment),</description>
          <population>subjects who completed Epclusa treatment and had HCV RNA measured 12 weeks after completion of treatment</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Health-Related Quality of Life</title>
        <description>Change in mean score on 5-point LIkert Scale to statement &quot;My Health is Excellent&quot; (1=definitely true, 5=definitely false) from baseline and 12 weeks post-treatment</description>
        <time_frame>Baseline and 12 weeks post treatment</time_frame>
        <population>Subjects who completed questionnaire at baseline and 12 weeks after completion of treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Single Arm Intervention</title>
            <description>Subjects who completed baseline and 12-week post treatment questionnaire</description>
          </group>
        </group_list>
        <measure>
          <title>Health-Related Quality of Life</title>
          <description>Change in mean score on 5-point LIkert Scale to statement &quot;My Health is Excellent&quot; (1=definitely true, 5=definitely false) from baseline and 12 weeks post-treatment</description>
          <population>Subjects who completed questionnaire at baseline and 12 weeks after completion of treatment</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.44" lower_limit="-1" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adherence to Study Treatment</title>
        <description>To assess adherence to velpatasvir/sofosbuvir therapy among participants administered treatment in the context of visits to an outpatient addiction clinic for buprenorphine/naloxone replacement therapy and mental health care.</description>
        <time_frame>This outcome measure will be assessed for each participant during a 12 week course of study treatment.</time_frame>
        <population>The 8 subjects who completed treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Single Arm Intervention</title>
            <description>12-week Epclusa Treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Adherence to Study Treatment</title>
          <description>To assess adherence to velpatasvir/sofosbuvir therapy among participants administered treatment in the context of visits to an outpatient addiction clinic for buprenorphine/naloxone replacement therapy and mental health care.</description>
          <population>The 8 subjects who completed treatment</population>
          <units>% of prescribed doses taken</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94" lower_limit="83.7" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>This was a single arm intervention study with a very small number of participants. Therefore, only descriptive statistics are provided.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>There was no comparator arm in this small single arm study</non_inferiority_desc>
            <other_analysis_desc>No confidence intervals around point estimates provided given very small number of participants</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From study entrance through treatment period</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Single Arm Intervention</title>
          <description>12-week Epclusa Treatment</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-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="11"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Altered Mental Status</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Visual Hallucination</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicidal Ideation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="3" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>GI distress</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Scabies</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Small number of subjects analyzed</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Amy E. Colson, MD</name_or_title>
      <organization>Community Research Initiative of New England</organization>
      <phone>6175021700</phone>
      <email>acolson@crine.org</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/NCT03235154
org study id: 15-05
nct id: NCT03235154
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The main purpose of this pilot study is to investigate the safety, effectiveness and
      tolerability of the study medication in the treatment of people with chronic hepatitis C
      virus infection who regularly attend a psychiatrist-staffed clinic for opiate addiction
      treatment.
An estimated 3.2 million people in the United States are currently infected with hepatitis C
      virus (HCV). Since 1990, when the US introduced screening of the blood supply for HCV,
      injection drug use has been the primary mode of HCV transmission in the United States. It is
      widely recognized that addressing the HCV epidemic among people who inject drugs (PWID)
      depends on increasing access to: 1) clean injection equipment; 2) opiate substitution therapy
      (OST); 3) curative HCV treatment; and 4) assistance with comorbid psychiatric conditions and
      social issues (Robaeys, C et al, 2013).

      Nevertheless, access to HCV treatment among current and former injection drug users is
      thought to be limited by several factors including: 1) insufficient number of infectious
      disease and gastroenterology providers and 2) provider and third-party payor concerns about
      adherence to medication and the risk of reinfection (Aspinall, EJ et al, 2013). Strategies to
      increase access among current and former injection drug users to direct acting antiviral
      drugs are urgently needed. The purpose of the current study is to assess the impact of
      co-treating chronic hepatitis C infection and opiate dependence within the context of an
      outpatient addiction clinic staffed by psychiatrists. The beneficial impact of co-treating
      opiate dependence and an infectious illness has been demonstrated in the case of HIV
      infection. Altice and colleagues conducted an observational study of HIV-infected
      opiate-dependent patients who were offered OST with buprenorphine/naloxone at 10 different
      HIV clinics. Subjects initiating buprenorphine/naloxone were more likely to initiate or
      remain on ART (antiretroviral therapy) (Altice, 2011).

      The Extension for Community Healthcare Outcomes (ECHO) program has demonstrated that with
      proper training and mentorship, primary care providers with no prior experience in managing
      HCV are able to treat the disease effectively (Arora et al, 2011). Since the publication of
      the ECHO study, the treatment of HCV has become considerably less complicated due to the
      widespread availability of safe, highly effective single tablet regimens, such as Epclusa.
      The investigators believe that treatment of HCV is now well within the grasp of physicians
      and other healthcare providers without training in internal or family medicine.

      This single arm pilot study will assess HCV treatment with Epclusa at an outpatient addiction
      clinic staffed by psychiatrists. The investigators hypothesize that with proper training and
      mentorship, psychiatrists who are also a licensed buprenorphine/naloxone providers will be
      able to effectively assess liver health and treat chronic hepatitis C infection with Epclusa.
      Further, the investigators hypothesize that patients with chronic hepatitis C infection on
      buprenorphine/naloxone maintenance therapy who are treated for HCV by a psychiatrist during
      regularly scheduled visits to an addiction clinic will have high rates of adherence to HCV
      treatment and achieve SVR12 (sustained virologic response, 12 weeks post-treatment).

      Given that subjects will receive standard of care evaluation and treatment for their chronic
      hepatitis C infection, the investigators believe that study participation poses minimal risk.
      Indeed, The investigators believe that subjects will benefit from improved access to this
      important treatment which will be provided at a convenient location by a known physician
      under the guidance of an infectious disease physician with extensive experience treating HCV
      infection.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Sustained Virologic Response at 12 Weeks Post Treatment (SVR-12)
time frame: This outcome measure will be assessed for each participant 12 weeks after completion of a 12 week course of treatment
description: To assess the effectiveness of HCV treatment with velpatasvir/sofosbuvir administered by psychiatrist/licensed buprenorphine/naloxone providers during regularly scheduled visits to an outpatient addiction clinic for buprenorphine/naloxone replacement therapy and mental healthcare, as measured by percentage of patients achieving SVR-12 (defined as HCV RNA < lower limit of quantification (LLOQ) 12 weeks after discontinuation of study treatment),
measure: Health-Related Quality of Life
time frame: Baseline and 12 weeks post treatment
description: Change in mean score on 5-point LIkert Scale to statement "My Health is Excellent" (1=definitely true, 5=definitely false) from baseline and 12 weeks post-treatment
measure: Adherence to Study Treatment
time frame: This outcome measure will be assessed for each participant during a 12 week course of study treatment.
description: To assess adherence to velpatasvir/sofosbuvir therapy among participants administered treatment in the context of visits to an outpatient addiction clinic for buprenorphine/naloxone replacement therapy and mental health care.
arm group label: Treatment Arm
arm group type: Other
description: In this open label, single arm study, all subjects will receive the intervention as prescribed by psychiatrists in the office based opiate addition treatment program.
intervention type: Drug
intervention name: sofosbuvir/velpatasvir
description: 12 week treatment with once daily sofosbuvir/velpatasvir fixed dose combination therapy. Tablets are formulated with 400mg sofosbuvir and 100mg velpatasvir in pink, diamond-shaped, film coated tablets.
arm group label: Treatment Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Amy E Colson, MD MPH
role: Principal Investigator
affiliation: Community Research Initiative of New England
facility: 
country: United States
citation: Altice FL, Bruce RD, Lucas GM, Lum PJ, Korthuis PT, Flanigan TP, Cunningham CO, Sullivan LE, Vergara-Rodriguez P, Fiellin DA, Cajina A, Botsko M, Nandi V, Gourevitch MN, Finkelstein R; BHIVES Collaborative. HIV treatment outcomes among HIV-infected, opioid-dependent patients receiving buprenorphine/naloxone treatment within HIV clinical care settings: results from a multisite study. J Acquir Immune Defic Syndr. 2011 Mar 1;56 Suppl 1(Suppl 1):S22-32. doi: 10.1097/QAI.0b013e318209751e.
PMID: 21317590
citation: Arora S, Thornton K, Murata G, Deming P, Kalishman S, Dion D, Parish B, Burke T, Pak W, Dunkelberg J, Kistin M, Brown J, Jenkusky S, Komaromy M, Qualls C. Outcomes of treatment for hepatitis C virus infection by primary care providers. N Engl J Med. 2011 Jun 9;364(23):2199-207. doi: 10.1056/NEJMoa1009370. Epub 2011 Jun 1.
PMID: 21631316
citation: Robaeys G, Grebely J, Mauss S, Bruggmann P, Moussalli J, De Gottardi A, Swan T, Arain A, Kautz A, Stover H, Wedemeyer H, Schaefer M, Taylor L, Backmund M, Dalgard O, Prins M, Dore GJ; International Network on Hepatitis in Substance Users. Recommendations for the management of hepatitis C virus infection among people who inject drugs. Clin Infect Dis. 2013 Aug;57 Suppl 2:S129-37. doi: 10.1093/cid/cit302.
PMID: 23884061
citation: Aspinall EJ, Corson S, Doyle JS, Grebely J, Hutchinson SJ, Dore GJ, Goldberg DJ, Hellard ME. Treatment of hepatitis C virus infection among people who are actively injecting drugs: a systematic review and meta-analysis. Clin Infect Dis. 2013 Aug;57 Suppl 2:S80-9. doi: 10.1093/cid/cit306.
PMID: 23884071
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis C, Chronic
mesh term: Hepatitis
mesh term: Opioid-Related Disorders
mesh term: Sofosbuvir
mesh term: Velpatasvir
mesh term: Sofosbuvir-velpatasvir drug combination
sharing ipd: No
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Small number of subjects analyzed
point of contact: 