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Sofosbuvir and Ledipasvir in HIV/HCV Coinfected Pre or Post Liver Transplant

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

Basic Trial Information

Phase Type Age Sponsor Protocol IDs Status
Phase 4 Interventional 18 Years and older University of California, San Francisco 12044
1U01AI115714
NCT02533934
Enrolling patients

Study Design:


Principal Investigator

Professor of Surgery
Surgical Director, Kidney and Pancreas Transplant Program
Surgical Director, Pediatric Renal Transplant Program
Co-Director, Pancreatic Islet Cell Transplant Program
Chair, Department of Surgery Research Committee
Program, Director, T32 Training Program in Transplant Surgery

Clinical Research Coordinator

UCSF Medical Center at Parnassus
(415) 514-6454 Phone
(415) 476-6964 Fax

Trial Summary

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

Eligibility

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:
       Non-childbearing potential
       Childbearing potential, has a negative urine pregnancy test at day 0 prior to
       dosing, and agrees to acceptable birth control
     3. 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)
     4. Have HIV-1 infection and either:
       On protocol approved HIV medications (antiretrovirals) for at least 4 weeks WITH
       an HIV viral load less than the level of detection OR
       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
     5. 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
     6. HCV genotype 1, 3, 4, or 6
     7. Able to effectively communicate with the Investigator and other center personnel.
     8. Willing to give written informed consent and comply with the study restrictions and
         requirements.
     9. NIH ONLY: Have a primary transplant hepatologist outside of the NIH for medical
         management.
     10. Willingness to allow stored blood or tissue samples to be used in the future for
         studying liver disease and immune function.
     11. Willingness to permit HLA typing to be performed.
     12. 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

Detailed Description

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

Important

Final eligibility is determined by the health professionals conducting the trial and the protocol approved by the Committee on Human Resources (CHR) at the University of California, San Francisco (UCSF). The Patient Consent Form for this trial is available upon request. For more information about this trial, please see the full posting at ClinicalTrials.gov.

Information about this trial was obtained from the NIH Clinical Trials website, http://clinicaltrials.gov on 3/15/2017. UCSF specific information including the PI (Principal Investigator), trial enrollment status, and UCSF Study ID, supplement the ClinicalTrials.gov study posting.
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