<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/NCT02206932</url>
  </required_header>
  <id_info>
    <org_study_id>TMC435HPC2008</org_study_id>
    <nct_id>NCT02206932</nct_id>
  </id_info>
  <brief_title>A Study of the Safety and Effectiveness of Simeprevir and Sofosbuvir for Patients With HIV and Hepatitis C</brief_title>
  <official_title>An Open Label, Pilot Study to Investigate the Safety and Efficacy of 12 Weeks of Simeprevir and Sofosbuvir, for HIV-infected, HCV Genotype 1 Patients With Advanced Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Janssen Scientific Affairs, LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a study of the safety and effectiveness of the hepatitis C medications sofosbuvir and&#xD;
      simeprevir in patients who have both the HIV and hepatitis C (HCV) viruses.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a research study of an investigational combination of two hepatitis C medications&#xD;
      call sofosbuvir (SOF) and simeprevir (SMV). Both medications are approved by the U.S. Food&#xD;
      and Drug Administration (FDA) for treatment of hepatitis C in combination with other&#xD;
      medications. The combination sofosbuvir and simeprevir has not been approved by the FDA and&#xD;
      is being tested as an investigational combination in research studies such as this. The&#xD;
      purpose of this study is to see if SOF + SMV given for 12 weeks is safe and able to clear the&#xD;
      Hepatitis C virus (HCV) from subjects who are co-infected with HIV-1 and who have scarring of&#xD;
      the liver (fibrosis of 3 or 4 on a scale of 0-4, with 4 as the most scarring, also known as&#xD;
      cirrhosis).&#xD;
&#xD;
      This study is an investigator-initiated clinical trial sponsored by University of California,&#xD;
      San Francisco (UCSF), with support and the study drug simeprevir provided by Janssen&#xD;
      Scientific Affairs, LLC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    never opened&#xD;
  </why_stopped>
  <start_date type="Anticipated">August 2014</start_date>
  <completion_date type="Anticipated">December 2015</completion_date>
  <primary_completion_date type="Anticipated">September 2015</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>SVR12 (HCV RNA &lt;LLOQ, or lower limit of quantification)</measure>
    <time_frame>12 weeks after discontinuation of study treatment</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Hepatitis C, Chronic</condition>
  <condition>HIV CDC Category A1</condition>
  <arm_group>
    <arm_group_label>Sofosbuvir + Simeprevir</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Subjects will be enrolled and treated with simeprevir 150 mg and sofosbuvir 400 mg once daily for 12 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sofosbuvir + Simeprevir</intervention_name>
    <arm_group_label>Sofosbuvir + Simeprevir</arm_group_label>
    <other_name>Sovaldi</other_name>
    <other_name>Olysio</other_name>
    <other_name>TMC435</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing and able to provide written informed consent&#xD;
&#xD;
          -  Male or female, age ≥ 18 years&#xD;
&#xD;
          -  Body mass index (BMI) ≥ 18 kg/m2&#xD;
&#xD;
          -  HCV RNA ≥ 104 IU/mL at Screening&#xD;
&#xD;
          -  HCV genotype 1 at screening or with prior documentation. Any non-definitive genotype&#xD;
             results will exclude the subject from study participation&#xD;
&#xD;
          -  Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy&#xD;
&#xD;
          -  Fibrosis determination: Fibrosis of Metavir F3/F4 may be established by one of the&#xD;
             following:&#xD;
&#xD;
               1. Liver biopsy at any point in time with Metavir score F3/F4, or equivalent on an&#xD;
                  alternative scale.&#xD;
&#xD;
               2. Fibroscan ≥ 9.5 kPA&#xD;
&#xD;
               3. FibroSURE: ≥ 0.58&#xD;
&#xD;
          -  Liver imaging within 12 months prior to Baseline/Day 1 is required in subjects with&#xD;
             known cirrhosis to exclude hepatocellular carcinoma (HCC). Acceptable liver imaging&#xD;
             includes ultrasound, CT scan or MRI.&#xD;
&#xD;
          -  HCV treatment status of one of the following:&#xD;
&#xD;
               1. HCV Treatment-Naive: No prior exposure to any IFN, RBV, or other approved or&#xD;
                  experimental HCV-specific DAA agents&#xD;
&#xD;
               2. HCV Treatment-Experienced: Virologic failure after treatment with PEG-IFN+RBVor&#xD;
                  standard IFN +RBV. Prior exposure to HCV polymerase or protease inhibitors is&#xD;
                  exclusionary. Prior treatment experienced patients will be categorized as one of&#xD;
                  the following:&#xD;
&#xD;
             i. HCV Treatment-Intolerant: Subjects that discontinued HCV treatment due to&#xD;
             development or significant worsening of a treatment related adverse event ii. Null&#xD;
             responder: HCV RNA &lt; 2 log10 decline during first 12 weeks of treatment iii. Partial&#xD;
             responder: HCV RNA ≥ 2 log10 decline during first 12 weeks of treatment but stopped&#xD;
             therapy due to inadequate virologic response iv. Relapse : Undetectable HCV RNA (HCV&#xD;
             RNA &lt;LLOQ) on treatment, but experienced breakthrough or relapse&#xD;
&#xD;
          -  HIV-1 infection as documented by HIV-1 antibody at screening or any time prior to&#xD;
             screening&#xD;
&#xD;
          -  HIV treatment status: For subject receiving ART, HIV RNA must be &lt; 40 copies/ml at&#xD;
             screening and &lt;200 copies/ml for at least 12 weeks prior to screening. Changes in&#xD;
             therapy during the 12 weeks prior to enrollment permitted as long as not due to HIV&#xD;
             treatment failure.&#xD;
&#xD;
          -  HIV ART allowed in this study are the following and should be administered per the&#xD;
             prescribing information in the package insert:&#xD;
&#xD;
               -  NRTIs: emtricitabine, lamivudine, tenofovir, abacavir&#xD;
&#xD;
               -  Maraviroc&#xD;
&#xD;
               -  Integrase inhibitors: dolutegravir or raltegravir&#xD;
&#xD;
               -  NNRTI's: rilpivirine&#xD;
&#xD;
               -  Enfuvitide Fixed dose combinations are permitted.&#xD;
&#xD;
          -  Screening ECG without clinically significant abnormalities&#xD;
&#xD;
          -  Subjects must have the following laboratory parameters at Screening and at Pre-entry&#xD;
             (if pre-entry visit is required):&#xD;
&#xD;
               -  CD4 T-cell count &gt;100 cells/mm3 if on ART, ≥ 350 cells/mm3 if not on ART&#xD;
&#xD;
               -  ALT ≤10 x the upper limit of normal (ULN)&#xD;
&#xD;
               -  AST ≤10 x ULN&#xD;
&#xD;
               -  Direct bilirubin ≤1.5 ULN&#xD;
&#xD;
               -  Creatinine clearance (CrClr) ≥50 mL /min, as calculated by the Cockcroft-Gault&#xD;
                  equation&#xD;
&#xD;
               -  Hemoglobin ≥10 g/dL&#xD;
&#xD;
               -  Albumin ≥3g/dL&#xD;
&#xD;
               -  INR ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an&#xD;
                  anticoagulant regimen affecting INR&#xD;
&#xD;
               -  Alpha feto protein (AFP) levels &lt;50. If ≥ 50, they should have a liver imaging&#xD;
                  study (eg, ultrasound, CT scan, MRI) showing no evidence of hepatocellular&#xD;
                  carcinoma within 3 months of study enrollment&#xD;
&#xD;
          -  Female subjects of reproductive potential (defined as women who have not been&#xD;
             post-menopausal for at least 24 consecutive months, ie, who have had menses within the&#xD;
             preceding 24 months, or women who have not undergone surgical sterilization,&#xD;
             specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy)&#xD;
             must have a negative serum pregnancy test with a sensitivity of at least 25 mIU/mL&#xD;
             performed during screening, within 48 hours prior to study entry.&#xD;
&#xD;
          -  All subjects must agree not to participate in a conception process (eg, active attempt&#xD;
             to become pregnant or to impregnate, sperm donation, in vitro fertilization).&#xD;
&#xD;
        NOTE: Female candidates who are pregnant or breastfeeding are not eligible. A male&#xD;
        candidate who has a pregnant female partner is not eligible for the study.&#xD;
&#xD;
          -  When participating in sexual activity that could lead to pregnancy, all subjects must&#xD;
             agree to use at least two non-hormonal forms of contraceptive simultaneously while&#xD;
             receiving protocol-specified medications, and for 4 weeks after stopping the&#xD;
             medications. Such methods include:&#xD;
&#xD;
               -  Condoms (male or female) with or without a spermicidal agent&#xD;
&#xD;
               -  Diaphragm or cervical cap with spermicide&#xD;
&#xD;
               -  Intrauterine device (IUD)&#xD;
&#xD;
               -  Tubal ligation NOTE: Providers and subjects should be advised that not all&#xD;
                  contraceptive choices listed above can prevent HIV transmission and that some may&#xD;
                  actually increase the risk of HIV acquisition. Study subjects who are sexually&#xD;
                  active with HIV-1 negative or unknown HIV-1 serostatus partners should be advised&#xD;
                  that they need to consider effective strategies for reducing the risk of HIV&#xD;
                  transmission, as well as meeting the requirement for effective contraception&#xD;
                  during their participation in the study. Study subjects should discuss&#xD;
                  contraceptive choices and HIV risk reduction methods with their health care&#xD;
                  provider.&#xD;
&#xD;
          -  Subjects who are not of reproductive potential (women who have been post-menopausal&#xD;
             for at least 24 consecutive months or have undergone hysterectomy and/or bilateral&#xD;
             oophorectomy or salpingectomy or men who have documented azoospermia or undergone&#xD;
             vasectomy) are eligible without requiring the use of contraceptives. Acceptable&#xD;
             documentation of sterilization and menopause is specified below.&#xD;
&#xD;
        Written or oral documentation communicated by clinician or clinician's staff of one of the&#xD;
        following:&#xD;
&#xD;
          -  Physician report/letter&#xD;
&#xD;
          -  Operative report or other source documentation in the patient record (a laboratory&#xD;
             report of azoospermia is required to document successful vasectomy)&#xD;
&#xD;
          -  Discharge summary&#xD;
&#xD;
          -  Follicle stimulating hormone-release factor (FSH) measurement elevated into the&#xD;
             menopausal range as established by the reporting laboratory.&#xD;
&#xD;
               -  Subject must be able to comply with the dosing instructions for study drug&#xD;
                  administration and able to complete the study schedule of assessments.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hepatic decompensation at any point in time (includes variceal bleeding, hepatic&#xD;
             encephalopathy, and ascites)&#xD;
&#xD;
          -  HBs Ag +&#xD;
&#xD;
          -  Prior HCV treatment with an HCV protease inhibitor or HCV polymerase inhibitor&#xD;
             including sofosbuvir&#xD;
&#xD;
          -  Other known causes of significant liver disease including chronic or acute hepatitis&#xD;
             B, acute hepatitis A, hemochromatosis, or homozygote alpha-1 antitrypsin deficiency.&#xD;
&#xD;
          -  Serious illness including malignancy within 24 weeks prior to study entry, or other&#xD;
             chronic medical conditions that in the opinion of the site investigator may preclude&#xD;
             completion of the protocol.&#xD;
&#xD;
          -  Presence of active or acute AIDS-defining opportunistic infections within 12 weeks&#xD;
             prior to study entry.&#xD;
&#xD;
          -  Use of any prohibited concomitant medications&#xD;
&#xD;
          -  Child-Pugh Score 6.2.2 Pre-entry&gt;6&#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>Anne Luetkemeyer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>San Francisco General Hospital, University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://hiv.ucsf.edu/</url>
    <description>Positive Health Program, San Francisco General Hospital/University of California, San Francisco</description>
  </link>
  <reference>
    <citation>Kirk GD, Mehta SH, Astemborski J, Galai N, Washington J, Higgins Y, Balagopal A, Thomas DL. HIV, age, and the severity of hepatitis C virus-related liver disease: a cohort study. Ann Intern Med. 2013 May 7;158(9):658-66. doi: 10.7326/0003-4819-158-9-201305070-00604.</citation>
    <PMID>23440167</PMID>
  </reference>
  <reference>
    <citation>Sulkowski MS, Mehta SH, Torbenson MS, Higgins Y, Brinkley SC, de Oca RM, Moore RD, Afdhal NH, Thomas DL. Rapid fibrosis progression among HIV/hepatitis C virus-co-infected adults. AIDS. 2007 Oct 18;21(16):2209-16. doi: 10.1097/QAD.0b013e3282f10de9.</citation>
    <PMID>18090048</PMID>
  </reference>
  <reference>
    <citation>Osinusi A, Meissner EG, Lee YJ, Bon D, Heytens L, Nelson A, Sneller M, Kohli A, Barrett L, Proschan M, Herrmann E, Shivakumar B, Gu W, Kwan R, Teferi G, Talwani R, Silk R, Kotb C, Wroblewski S, Fishbein D, Dewar R, Highbarger H, Zhang X, Kleiner D, Wood BJ, Chavez J, Symonds WT, Subramanian M, McHutchison J, Polis MA, Fauci AS, Masur H, Kottilil S. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA. 2013 Aug 28;310(8):804-11. doi: 10.1001/jama.2013.109309. Erratum In: JAMA. 2013 Nov 13;310(18):1987. Dosage error in article text.</citation>
    <PMID>23982366</PMID>
  </reference>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>July 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <last_update_submitted>June 11, 2019</last_update_submitted>
  <last_update_submitted_qc>June 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatitis C</keyword>
  <keyword>HIV</keyword>
  <keyword>Simeprevir</keyword>
  <keyword>Sofosbuvir</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sofosbuvir</mesh_term>
    <mesh_term>Simeprevir</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02206932
org study id: TMC435HPC2008
nct id: NCT02206932
lead sponsor: 
collaborator: 
has dmc: No
This is a study of the safety and effectiveness of the hepatitis C medications sofosbuvir and
      simeprevir in patients who have both the HIV and hepatitis C (HCV) viruses.
This is a research study of an investigational combination of two hepatitis C medications
      call sofosbuvir (SOF) and simeprevir (SMV). Both medications are approved by the U.S. Food
      and Drug Administration (FDA) for treatment of hepatitis C in combination with other
      medications. The combination sofosbuvir and simeprevir has not been approved by the FDA and
      is being tested as an investigational combination in research studies such as this. The
      purpose of this study is to see if SOF + SMV given for 12 weeks is safe and able to clear the
      Hepatitis C virus (HCV) from subjects who are co-infected with HIV-1 and who have scarring of
      the liver (fibrosis of 3 or 4 on a scale of 0-4, with 4 as the most scarring, also known as
      cirrhosis).

      This study is an investigator-initiated clinical trial sponsored by University of California,
      San Francisco (UCSF), with support and the study drug simeprevir provided by Janssen
      Scientific Affairs, LLC.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: SVR12 (HCV RNA <LLOQ, or lower limit of quantification)
time frame: 12 weeks after discontinuation of study treatment
arm group label: Sofosbuvir + Simeprevir
arm group type: Other
description: Subjects will be enrolled and treated with simeprevir 150 mg and sofosbuvir 400 mg once daily for 12 weeks
intervention type: Drug
intervention name: Sofosbuvir + Simeprevir
arm group label: Sofosbuvir + Simeprevir
other name: Sovaldi
other name: Olysio
other name: TMC435
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anne Luetkemeyer, MD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
country: United States
url: http://hiv.ucsf.edu/
description: Positive Health Program, San Francisco General Hospital/University of California, San Francisco
citation: Kirk GD, Mehta SH, Astemborski J, Galai N, Washington J, Higgins Y, Balagopal A, Thomas DL. HIV, age, and the severity of hepatitis C virus-related liver disease: a cohort study. Ann Intern Med. 2013 May 7;158(9):658-66. doi: 10.7326/0003-4819-158-9-201305070-00604.
PMID: 23440167
citation: Sulkowski MS, Mehta SH, Torbenson MS, Higgins Y, Brinkley SC, de Oca RM, Moore RD, Afdhal NH, Thomas DL. Rapid fibrosis progression among HIV/hepatitis C virus-co-infected adults. AIDS. 2007 Oct 18;21(16):2209-16. doi: 10.1097/QAD.0b013e3282f10de9.
PMID: 18090048
citation: Osinusi A, Meissner EG, Lee YJ, Bon D, Heytens L, Nelson A, Sneller M, Kohli A, Barrett L, Proschan M, Herrmann E, Shivakumar B, Gu W, Kwan R, Teferi G, Talwani R, Silk R, Kotb C, Wroblewski S, Fishbein D, Dewar R, Highbarger H, Zhang X, Kleiner D, Wood BJ, Chavez J, Symonds WT, Subramanian M, McHutchison J, Polis MA, Fauci AS, Masur H, Kottilil S. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA. 2013 Aug 28;310(8):804-11. doi: 10.1001/jama.2013.109309. Erratum In: JAMA. 2013 Nov 13;310(18):1987. Dosage error in article text.
PMID: 23982366
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis C, Chronic
mesh term: Hepatitis
mesh term: Sofosbuvir
mesh term: Simeprevir