Clinical Trials

MainTitle

Sofosbuvir Based DAA Therapy in HIV/HCV Coinfected Pre or Post Liver Transplant (STOP-CO)

This study is currently recruiting participants. (see Contacts and Locations)

Verified January 2018 by Peter Stock, University of California, San Francisco

Sponsor
University of California, San Francisco

Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)
Icahn School of Medicine at Mount Sinai
Columbia University
University of Pennsylvania
University of Maryland
Georgetown University
Johns Hopkins University
National Institutes of Health Clinical Center (CC)

Information provided by (Responsible Party)
Peter Stock, University of California, San Francisco

ClinicalTrials.gov Identifier
NCT02533934

First received: August 25, 2015
Last updated: January 29, 2018
Last Verified: January 2018
History of Changes
Purpose

Purpose

Retrospective/Prospective, open-label study using sofosbuvir based DAA therapy to treat HIV/HCV coinfected pre or post liver transplant participants

Condition Intervention Phase
HIV
Hepatitis C
Cirrhosis

Drug : Harvoni
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Retrospective/Prospective Cohort Study to Assess Safety, Tolerability, and Efficacy of Sofosbuvir Based Direct Acting Antiviral (DAA) Therapy for Hepatitis C Treatment in HIV/HCV Coinfected Subjects Pre or Post Liver Transplant

Further study details as provided by Peter Stock, University of California, San Francisco:

Primary Outcome Measures

  • Proportion of subjects achieving SVR12 (HCV RNA [ Time Frame: 12 weeks post treatment ]
Secondary Outcome Measures:
  • Correlation of the slope of HCV viral load decline (early viral kinetics) with sustained virologic response at 24 weeks post-treatment (SVR24) [ Time Frame: 24 weeks post treatment ]
  • Proportion of subjects achieving SVR4 and SVR24 (HCV RNA < LLOQ at 4 and 24 weeks after completion of treatment) [ Time Frame: 4 and 24 weeks post treatment ]

Estimated Enrollment: 50
Study Start Date: August 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Study Drug
Treatment with Harvoni
Drug: Harvoni

Treatment of Hepatitis C with Harvoni

Other Name: SOF/LDV

Detailed Description:

Approximately fifty HIV/HCV coinfected patients with decompensated liver disease will be enrolled in the study. Ten (up to twenty) subjects will be treated with FDC SOF/LDV pre or post liver transplant and followed prospectively. Forty + subjects will be enrolled retrospectively with the intent to capture all patients who have been exposed to sofosbuvir based DAA therapies at participating sites since 1/2014, and to mirror the population being enrolled prospectively.
In addition, participants in the retrospective arm will be contacted to consent to one prospective study visit for liver staging to determine rates of reversal of decompensation, reversal of cirrhosis and improvements in graft survival post treatment, and for future contact by the NIH Clinical Center to assess longer term outcomes when this study ends.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

RETROSPECTIVE ARM INCLUSION CRITERIA
The intent of the Retrospective Arm is to capture all HIV/HCV coinfected patients exposed to sofosbuvir based DAA therapy since 2014, to mirror the population enrolled in the Prospective Arm.
Liver transplant candidates (listed) and decompensated cirrhotics (not listed) for liver transplant

  1. Treated with sofosbuvir based DAA for any duration since 2014
  2. Age >18 years at time of treatment
  3. Pre-treatment Child's Pugh score of 7 or greater
  4. Pre-treatment laboratory MELD >=6 and <=0
  5. Survived at least 12 weeks after start of treatment
  6. HIV-positive on stable ART for at least 4 weeks pre-treatment
  7. Chronic HCV infection with at least one measurement of plasma HCV RNA >= 1,000 IU/mL prior to treatment with sofosbuvir based DAA therapy
  8. HCV genotype 1, 4, 5 or 6

Liver transplant recipients
  • Treated with sofosbuvir based DAA post liver transplant for any duration since 2014
  • Liver transplant from 2000 to current
  • Age >18 years at time of treatment
  • Treated initiated at least 1 month post-liver transplant
  • Post-LT stage of liver disease documented within the prior year of treatment start date by standard of care methods of liver staging
  • Survived at least 12 weeks after start of treatment
  • HIV-positive on stable ART for at least 4 weeks pre-treatment
  • Chronic HCV infection with at least one measurement of plasma HCV RNA >= 1,000 IU/mL prior to treatment with sofosbuvir based DAA therapy
  • Fibrosis staging done within 1 year of start of DAA therapy
  • HCV genotype 1, 4, 5 or 6

  • PROSPECTIVE ARM INCLUSION/EXCLUSION CRITERIA
    Pre-liver transplant candidates
    • Enrollment will be targeted to occur at least 12 weeks prior to anticipated transplant date.
    • Screening laboratory MELD >=6 and <=20 (NIH) or <=30 (non-NIH sites)

    • Post-liver transplant recipients
    • Recipients with evidence of recurrent HCV viremia
    • Subjects with compensated and decompensated liver disease
    • Screening laboratory MELD >=6 and <=20 (NIH) or <=30 (non-NIH sites)
    • Life expectation of >12 weeks

    • Inclusion Criteria
      1. Over 18 years of age at screening
      2. Female participants of child bearing potential must have a negative urine pregnancy test at day 0 prior to dosing.
      3. Has received a liver transplant for HCV or has decompensated cirrhosis (Child's Pugh score of 7 or greater)
      4. Have HIV-1 infection and either:
        1. On HIV medications (antiretrovirals) for at least 4 weeks WITH
      5. An HIV viral load less than the level of detection OR ~#o2~ On no HIV medications for at least 8 weeks WITH:
    • A CD4 count of 500 cells/mm3 or more OR
    • HIV viral load of < 500 copies/mL with a stable CD4 count for at least 3 months
  • Chronic HCV infection as documented by at least one measurement of plasma HCV RNA >= 1,000 IU/mL during screening and at least one of the following:

  • A positive anti-HCV antibody, HCV RNA, or an HCV genotype test at least 12 months prior to baseline (Day 0) visit together with positive HCV RNA test
  • HCV genotype 1, 4, 5 or 6
  • The use of an anti-HCV positive donor is allowed for participants who have detectable HCV RNA at the time of transplant.
  • The use of an HIV+ donor is allowed if the participant is enrolled in an IRB approved HOPE Act protocol at the transplant site. If the HIV+ donor is also HCV co-infected, then the recipient must have detectable HCV RNA at the time of transplant.
  • Able to effectively communicate with the Investigator and other center personnel.
  • Willing to give written informed consent and comply with the study restrictions and requirements.
  • Willingness to allow stored blood or tissue samples to be used in the future for studying liver disease and immune function.
  • Willingness to permit HLA typing to be performed.
  • Have a transplant team available for all primary and transplant-related care.
  • If not yet transplanted: expected to be at least 12 weeks prior to transplant in order to complete treatment course.
  • If not yet transplanted: Must have prior standard of care liver staging consistent with F4.
  • If not yet transplanted: For pre-LT patients with HCC, they must meet Milan criteria at time of enrollment to be eligible
  • If post-liver transplant, must be at least 1 month since transplant procedure to begin treatment.
  • If post-liver transplant, liver disease staging must be documented within the prior year by standard of care methods of liver staging

  • Exclusion Criteria
  • Positive HBsAg or anti-HBc at screening.
  • History of any other clinically active chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, Wilson's disease, >=1 antitrypsin deficiency, alcoholic liver disease, and toxin exposures).
  • Treatment with unlicensed herbal/natural remedies suggested to be taken for hepatitis treatment, such as Milk thistle, St. Johns Wort or Cats Claw, within 28 days of start of treatment
  • Treatment with IFN, RBV, telaprevir or boceprevir or any other approved or experimental medication with known anti-HCV activity within 1 month prior to screening date
  • Any prior exposure to an HCV NS5a specific inhibitor
  • A personal history of or first degree relative with a history of Torsade de pointes.
  • Abnormal hematological and biochemical parameters, including:
    1. Hemoglobin < 8g/dL
    2. Estimated GFR, calculated by the CKD-EPI equation, <30 mL/min/ per 1.73 m2
    3. Sodium <120 mmol/L
  • History of major organ transplantation other than liver or kidney transplantation.
  • Difficulty with blood collection/poor venous access for phlebotomy that would prevent the collection of study required samples
  • Infection requiring systemic antibiotics at the time of screening
  • Active or recent history (≤ 6 months) of drug or alcohol abuse
  • Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug.
  • Donation or loss of more than 400 mL blood within 8 weeks prior to first dose administration.
  • Any medications prohibited (see table 2 in section 8.11) within 28 days prior to Day 0 visit and likely required during study treatment period
  • History of clinically significant drug allergy to nucleoside/nucleotide analogs.
  • History or current evidence of psychiatric illness, endocrine, immunologic disorder, pulmonary, cardiac disease, seizure disorder, cancer or other conditions that in the opinion of the investigator makes the patient unsuitable for the study. Chronic medical conditions, especially if treated with medications (such as hypertension), must be stable at the time of screening. No new therapies should be started within 28 days prior to the study that may confound the assessment of study drug safety.
  • Participation in a clinical study (other than an IRB approved HOPE Act protocol involving the utilization of an HIV+ donor) in which an investigational drug, biologic, or device was received within 12 weeks prior to first dose administration.
  • Pregnant/Breastfeeding women

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT02533934

    Contacts

    Contact:   Rodney Rogers 415-514-6454 Rodney.Rogers@ucsf.edu

    Locations

    United States, California
    University of California, San Francisco Recruiting
    San Francisco, California, United States, 94143
    Contact: Rae Davis    415-514-3274    Rayshawnda.Davis@ucsf.edu
    Principal Investigator: Peter Stock, MD, PhD
    Sub-Investigator: Norah Terrault, MD
    Sub-Investigator: Marion Peters, MD
    United States, District of Columbia
    Georgetown University Recruiting
    Washington, District of Columbia, United States, 20057
    Contact: Takada Harris    202-444-6395    Takada.M.Harris@gunet.georgetown.edu
    Principal Investigator: Coleman I Smith, MD
    Sub-Investigator: Thomas Fishbein, MD
    United States, Maryland
    University of Maryland Recruiting
    Baltimore, Maryland, United States, 21201
    Contact: Ilise Marrazzo    410-706-2564    imarrazzo@ihv.umaryland.edu
    Principal Investigator: Robert Redfield, MD
    Sub-Investigator: Shyamasundaran Kottilil, MD
    Sub-Investigator: Jennifer Husson, MD
    Johns Hopkins Medical Center Recruiting
    Baltimore, Maryland, United States, 21287
    Contact: Stephanie Katz    443-287-9605    ssneddo2@jhmi.edu
    Principal Investigator: Mark Sulkowski, MD
    Sub-Investigator: Christine Durand, MD
    National Institutes of Health Clinical Center Recruiting
    Bethesda, Maryland, United States, 20892
    Contact: Mary McLaughlin, RN, BSN    301-435-8001    MMCLAUGHLI@niaid.nih.gov
    Contact: Maryellen McManus    301-326-9711    maryellen.mcmanus@nih.gov
    Principal Investigator: Henry Masur, MD
    United States, New York
    Mt. Sinai Medical Center Recruiting
    New York, New York, United States, 10029
    Contact: Brandy Haydel    212-241-0255    Brandy.Haydel@mountsinai.org
    Principal Investigator: Shirish Huprikar, MD
    Sub-Investigator: Sander Florman, MD
    Columbia University Recruiting
    New York, New York, United States, 10032
    Contact: Moury Minhaz    212-305-3839    mm3597@cumc.columbia.edu
    Principal Investigator: Lorna Dove, MD
    Sub-Investigator: Jean Emond, MD
    United States, Pennsylvania
    University of Pennsylvania Recruiting
    Philadelphia, Pennsylvania, United States, 19104
    Contact: Maryann Najdzinowicz    212-662-4007    maryann.najdzinowicz@uphs.upenn.edu
    Principal Investigator: Emily Blumberg, MD
    Sub-Investigator: Kim Olthoff, MD
    Sub-Investigator: Christine Hsu, MD

    Sponsors and Collaborators

    University of California, San Francisco
    National Institute of Allergy and Infectious Diseases (NIAID)
    Icahn School of Medicine at Mount Sinai
    Columbia University
    University of Pennsylvania
    University of Maryland
    Georgetown University
    Johns Hopkins University
    National Institutes of Health Clinical Center (CC)

    Investigators

    Principal Investigator: Peter Stock, MD, PhD University of California, San Francisco
    Principal Investigator: Henry Masur, MD National Institutes of Health Clinical Center (CC)
    More Information

    More Information


    Responsible Party: Peter Stock, Professor in Residence, University of California, San Francisco  
    ClinicalTrials.gov Identifier: NCT02533934   History of Changes  
    Other Study ID Numbers: 12044  
      1U01AI115714  
    Study First Received: August 25, 2015  
    Last Updated: January 29, 2018  
    Individual Participant Data    
    Plan to Share IPD: Undecided  

    Keywords provided by Peter Stock, University of California, San Francisco:

    HIV
    Hepatitis C
    Liver Disease
    HCV Treatment
    transplant

    Additional relevant MeSH terms:
    Hepatitis
    Hepatitis A
    Hepatitis C
    Sofosbuvir
    Ledipasvir, sofosbuvir drug combination

    ClinicalTrials.gov processed this data on July 20, 2018
    This information is provided by ClinicalTrials.gov.