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Sofosbuvir Based DAA Therapy in HIV/HCV Coinfected Pre or Post Liver Transplant

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

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

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

Eligibility

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

     1. Treated with sofosbuvir based DAA post liver transplant for any duration since 2014
     2. Liver transplant from 2000 to current
     3. Age >18 years at time of treatment
     4. Treated initiated at least 1 month post-liver transplant
     5. Post-LT stage of liver disease documented within the prior year of treatment start
         date by standard of care methods of liver staging
     6. Survived at least 12 weeks after start of treatment
     7. HIV-positive on stable ART for at least 4 weeks pre-treatment
     8. Chronic HCV infection with at least one measurement of plasma HCV RNA >= 1,000 IU/mL
         prior to treatment with sofosbuvir based DAA therapy
     9. Fibrosis staging done within 1 year of start of DAA therapy
     10. 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:
       On 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
          - 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, 4, 5 or 6
     7. The use of an anti-HCV positive donor is allowed for participants who have detectable
         HCV RNA at the time of transplant.
     8. 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.
     9. Able to effectively communicate with the Investigator and other center personnel.
     10. Willing to give written informed consent and comply with the study restrictions and
         requirements.
     11. Willingness to allow stored blood or tissue samples to be used in the future for
         studying liver disease and immune function.
     12. Willingness to permit HLA typing to be performed.
     13. Have a transplant team available for all primary and transplant-related care.
     14. If not yet transplanted: expected to be at least 12 weeks prior to transplant in order
         to complete treatment course.
     15. If not yet transplanted: Must have prior standard of care liver staging consistent
         with F4.
     16. If not yet transplanted: For pre-LT patients with HCC, they must meet Milan criteria
         at time of enrollment to be eligible
     17. If post-liver transplant, must be at least 1 month since transplant procedure to begin
         treatment.
     18. If post-liver transplant, liver disease staging must be documented within the prior
         year by standard of care methods of liver staging
Exclusion Criteria

     1. Positive HBsAg or anti-HBc at screening.
     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 8.11) 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 (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.
     18. Pregnant/Breastfeeding women

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.

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 2/13/2018. 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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