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Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion:

Description

Summary

Pilot, open-label study using fixed dose combination of sofosbuvir /ledipasvir to treat HIV/HCV coinfected pre or post liver transplant participants

Official Title

A Pilot Study to Assess Safety, Tolerability, and Efficacy of Sofosbuvir and Ledipasvir for Hepatitis C Treatment in HIV/HCV Coinfected Subjects Pre or Post Liver Transplant

Details

Fifty HIV/HCV coinfected liver transplant candidates and recipients with HCV infection will be enrolled into this study. Approximately 25 pre-transplant and 25 post-transplant patients will be included.

The cohort of wait-listed patients with cirrhosis due to hepatitis C will be treated with SOF/LDV until LT or for a maximum of 24 weeks. Patients with and without HCC within Milan criteria are eligible.

Another cohort of liver transplant recipients with recurrent HCV infection post liver transplant will also be treated with SOF/LDV for a period of 12 weeks (no cirrhosis) or 24 weeks (cirrhosis). Patients with fibrosing cholestatic hepatitis are eligible and will be treated for 12 weeks.

Starting with Day 0, all subjects will receive SOF/LDV for 12 or up to 24 weeks. The total amount of time required to complete all the study visits is approximately 56 - 68 weeks from the screening period through the end of the follow-up visits:

  • Up to 8 weeks Screening period
  • 12 or 24 week treatment period
  • 12 and 24 week post-treatment follow-up visits (SVR12 and SVR24)
  • 36 weeks post-treatment to assess late viral relapse

Keywords

HIV Hepatitis C Cirrhosis Liver Disease HCV Treatment transplant Hepatitis Hepatitis A Sofosbuvir Ledipasvir Ledipasvir, sofosbuvir drug combination

Eligibility

For people ages 18 years and up

  1. Over 18 years of age at screening
  2. A female is allowed to enter and participate in the study if she is either of:
  3. Non-childbearing potential
  4. Childbearing potential, has a negative urine pregnancy test at day 0 prior to dosing, and agrees to acceptable birth control
  5. Has received a liver transplant for HCV or is wait-listed for liver transplantation due to complications of HCV-cirrhosis (must be approved for transplant and listed internally or with UNOS)
  6. Have HIV-1 infection and either:
  7. On protocol approved HIV medications (antiretrovirals) for at least 4 weeks WITH an HIV viral load less than the level of detection OR
  8. On no HIV medications for at least 8 weeks WITH a CD4 count of 500 cells/mm3 or more OR an HIV viral load of < 500 copies/mL with a stable CD4 count for at least 3 months
  9. 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

  1. HCV genotype 1, 3, 4, or 6
  2. Able to effectively communicate with the Investigator and other center personnel.
  3. Willing to give written informed consent and comply with the study restrictions and requirements.
  4. NIH ONLY: Have a primary transplant hepatologist outside of the NIH for medical management.
  5. . Willingness to allow stored blood or tissue samples to be used in the future for studying liver disease and immune function.
  6. . Willingness to permit HLA typing to be performed.
  7. . Have a transplant team responsible for all primary and transplant-related care.

Exclusion Criteria:

  1. Historically documented positive test at Screening for HBsAg, anti-HBc IgM Ab, and/or positive HBV DNA.
  2. 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).
  3. 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
  4. 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
  5. Any prior exposure to an HCV NS5a specific inhibitor
  6. A personal history of or first degree relative with a history of Torsade de pointes.
  7. Abnormal hematological and biochemical parameters, including:Hemoglobin < 8g/dL;Estimated GFR, calculated by the CKD-EPI equation, <30 mL/min/ per 1.73 m2; Sodium<120 mmol/L
  8. History of major organ transplantation other than liver or kidney transplantation.
  9. Difficulty with blood collection/poor venous access for phlebotomy that would prevent the collection of study required samples
  10. . Infection requiring systemic antibiotics at the time of screening
  11. . Active or recent history (≤ 6 months) of drug or alcohol abuse
  12. . Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug.
  13. . Donation or loss of more than 400 mL blood within 8 weeks prior to first dose administration.
  14. . Any medications prohibited (see table 2 in section 9.2) within 28 days prior to Day 0 visit and likely required during study treatment period
  15. . History of clinically significant drug allergy to nucleoside/nucleotide analogs.
  16. . 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.
  17. . Participation in a clinical study in which an investigational drug, biologic, or device was received within 12 weeks prior to first dose administration.
  18. . Pregnant/Breastfeeding women

Locations

  • University of California, San Francisco accepting new patients
    San Francisco, California, 94143, United States
  • National Institutes of Health Clinical Center accepting new patients
    Bethesda, Maryland, 20892, United States
  • Georgetown University accepting new patients
    Washington, District of Columbia, 20057, United States
  • University of Maryland accepting new patients
    Baltimore, Maryland, 21201, United States
  • Johns Hopkins Medical Center accepting new patients
    Baltimore, Maryland, 21287, United States
  • University of Pennsylvania accepting new patients
    Philadelphia, Pennsylvania, 19104, United States
  • Columbia University accepting new patients
    New York, New York, 10032, United States
  • Mt. Sinai Medical Center accepting new patients
    New York, New York, 10029, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT02533934
Phase
Phase 4
Lead Scientist
Peter Stock
Study Type
Interventional
Last Updated
December 2, 2016
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