Individuals with HIV-HCV co-infection and end-stage liver disease, with an indication for liver transplantation MedDRA version: 17.0 Level: HLT Classification code 10057212 Term: Hepatitis viral infections System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Sovaldi
Pharmaceutical Form: Tablet
Trade Name: Rebetol
Pharmaceutical Form: Capsule, hard
Sponsors
Università di Modena e ReggioEmilia
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Males or females at least 18 years old at Screening. Subjects or their heterosexual partner(s) must either be of non-childbearing potential or they must use effective contraception from 2 weeks before the initiation of therapy until 6 months after the last dose of study medication. 2.HIV-HCV Co-infection documented with HIV-Ab and HCV RNA positivity 2.1Chronic HCV-infection, any genotypes, documented by at least one measurement of serum HCV RNA above the lower limit of quantification (LLoQ) measured during Screening 2.2 Chronic HIV infection undergoing antiretroviral therapy for at least 6 month with HIV Viral Load =18 kg/m2. 6. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Any transplant patient who has agreed to a liver transplant from a live donor. 2. Patients requiring planned induction therapy with biologics post-transplantation or with a post-transplantation immunosuppressive regimen not consistent with: o Solumedrol/Prednisone o Tacrolimus (maintaining a serum level of 5-12 ng/mL) 3. Chronic medical conditions, especially if treated with medications (such as hypertension), must be stable at the time of screening and first dose. 4. Clinically significant ECG findings at screening, screening QTc = 500 ms (cirrhotic), or a personal or family history of Torsades de pointes 5. History of major organ transplantation with an existing functional graft. 6. Active substance abuse which, in the opinion of the investigator, would make the candidate inappropriate for participation in this study. 7. Abnormal hematological and biochemical parameters, including: a.neutrophil count 30 mg/dL g. serum albumin 2 8. History of clinically significant drug allergy to nucleoside/nucleotide analogs. 9. Participation in any other clinical trial within 3 months prior to screening visit and during the study 10. History of having received any systemic antineoplastic or immunomodulatory treatment (including radiation) within 3 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study (excluding a local regional therapy such as TACE). 11. Treatment with TACE or RFA within 30 days prior to the first dose. 12. Pregnant/Breastfeeding women or males whose partners are currently pregnant. 13. Poor venous access making the patient unable to complete the required laboratory testing schedule.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if the administration of a combination of sofosbuvir and ribavirin to HIV-HCV co-infected subjects prior to undergoing liver transplantation for up to 48 weeks (or the time of transplant) can prevent post-transplant HCV re-infection as determined by a sustained post-transplant virological response (HCV RNA <LLoQ) at 12 weeks post-transplant ;Secondary Objective: -To determine virological response in the pre-transplat period at 12 weeks after the end of treatment or at the day of liver transplantation -To determine the proportion of patients who get out from the transplant list due to resolution of end stage liver disease after completion of treatment -To assess safety and tolerability -To evaluate the HCV RNA Viral Kinetic during the treatment phase and following liver transplant and correlate results with the duration of treatment prior to liver transplant (LT). -To determine concentrations of SOF in the liver explants in a subset of patients who cease sofosbuvir therapy within 24 hours of LT. -To explore the presence of HCV RNA in the liver explants and to assess HCV sequences and to correlate with plasma HCV RNA kinetics during therapy, duration of therapy, duration of plasma HCV RNA negativity and cytokine mRNA expression in the liver - To assess patient and graft survival at 24 and 48 weeks post tranplant ;Primary end point(s): Sustained post-transplant virological response (HCV RNA <LLoQ) at 12 weeks post-transplant ;Timepoint(s) of evaluation of this end point: 12 weeks post-transplant | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 12 weeks after the end of treatment or at the day of liver transplantation ;Secondary end point(s): - HCV RNA <LLoQ in the pre-transplant period at 12 weeks after the end of treatment (48 weeks) or at the day of liver transplantation -patients proportion who get out from the transplant list - assess clinical and laboratory AE and SAE - HCV RNA viral kinetic during treatment and in the liver explants | — |
Countries
Italy
Contacts
Public ContactResearcher
Università di Modena e ReggioEmilia
Outcome results
None listed