Chronic Hepatitis C virus infection MedDRA version: 19.1 Level: PT Classification code 10019744 Term: Hepatitis C System Organ Class: 10021881 - Infections and infestations MedDRA version: 19.1 Level: PT Classification code 10008912 Term: Chronic hepatitis C System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Willing and able to provide written informed consent 2) Male or female age = 18 years 3) Chronic HCV infection (= 6 months) as documented by prior medical history or liver biopsy 4) HCV RNA = LLOQ at screening 5) End stage renal disease (ESRD) requiring peritoneal dialysis (PD) or hemodialysis (HD) 6) The most recent HCV treatment must have been completed at least 8 weeks prior to Screening 7) Subjects must have a determination of treatment experience (treatment naïve vs. treatment experienced). Treatment naïve is defined as having never been exposed to an approved or experimental HCV-specific direct acting antiviral agents or prior treatment of HCV with interferon or ribavirin. All other patients will be considered treatment experienced. 8) Subjects must have appropriate testing for determination of cirrhosis status. 9) Liver imaging within 6 months of Baseline/Day 1 is required in cirrhotic subjects only to exclude hepatocellular carcinoma (HCC) 10) Subjects with HIV-1 coinfection may be eligible, provided they satisfy additional inclusion criteria. 11) A negative serum pregnancy test is required for female subjects (unless permanently sterile or greater than two years post-menopausal). 12) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Appendix 4. 13) Lactating females must agree to discontinue nursing before the study drug is administered. 14) Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments. 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 95 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1) Current or prior history of any of the following: a) Clinically-significant illness b) Current or prior history of significant cardiac disease c) Gastrointestinal disorder or postoperative condition that could interfere with the absorption of the study drug. d) Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy. e) Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage). f) Solid organ transplantation other than failed kidney transplants (current use of =5 mg/day of prednisone, or equivalent dose of corticosteroid, allowed). g) Significant pulmonary disease h) Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 2 years. i) Malignancy within the 5 years prior to screening, with the exception of specific cancers that have been cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible 2) Screening ECG with clinically significant abnormalities 3) Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson’s disease, alfa 1 antitrypsin deficiency, cholangitis). 4) Infection with hepatitis B virus (HBV). 5) Opportunistic infection (reference Appendix 5) within 6 months prior to Screening 6) Infection (other than HIV or HCV) requiring parenteral therapy within 30 days prior to baseline. 7) Life threatening SAE during the screening period 8) Subjects has the following laboratory parameters at screening: a) ALT > 10 X the upper limit of normal (ULN) b) AST > 10 X ULN c) Direct bilirubin > 1.5 X ULN. For subjects receiving ritonavir boosted atazanavir regimen, a direct bilirubin > 1.5 xULN will be allowed if 9% f) Hemoglobin 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR i) Hepatitis B surface antigen positive 9) Prior exposure to any HCV NS5A inhibitor. 10) Male with pregnant female partner. 11) Females who may wish to become pregnant and/or plan to undergo egg harvesting during the course of the study and up to 30 days of the last dose of study drug 12) Males who may wish to donate sperm during the course of the study until at least 30 days after the last dose of study drug 13) Clinically-relevant alcohol or drug abuse within 12 months of screening. A positive drug screen will exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the investigator. 14) Use of any prohibited concomitant medications as described in Section 5.4. 15) Subjects with HIV-1 coinfection cannot be receiving an ARV regimen containing efavirenz (EFV) 16) Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent > 10 mg/day). 17) Known hypersensitivity to the VEL, SOF, the metabolites, or formulation excipient. 18) For subjects with HIV-1 coinfection only: • HIV-1 RNA >50 copies/mL • CD4 T-cell count <100 cells/mm3 • HIV-2 positive test
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the antiviral efficacy of treatment with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR12) • To evaluate the safety and tolerability of the treatment regimen ;Secondary Objective: • To determine the proportion of subjects who attain SVR at 4 and 24 weeks after cessation of the study treatment regimen (SVR4 and SVR24) • To evaluate the proportion of subjects with virologic failure • To evaluate the kinetics of circulating HCV RNA during treatment and after cessation of treatment • To evaluate the emergence of viral resistance to SOF and VEL during treatment and after cessation of treatment • To evaluate the steady-state pharmacokinetics of SOF and its metabolites and VEL in subjects who are on dialysis for End Stage Renal Disease (ESRD);Primary end point(s): The primary end point is SVR12 (HCV RNA < LLOQ 12 weeks after cessation of treatment) in the Full Analysis Set (FAS) population. The primary safety endpoint is any AE that led to permanent discontinuation of study drug. ;Timepoint(s) of evaluation of this end point: SVR 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The proportion of subjects with HCV RNA < LLOQ at 4 and 24 weeks after cessation of treatment (SVR4 and SVR24) • The proportion of subjects with HCV RNA < LLOQ on treatment • HCV RNA change from Baseline/Day 1 • The proportion of subjects with virologic failure • The proportion of subjects who develop viral resistance to SOF and VEL during treatment and after cessation of treatment • The steady-state pharmacokinetics of SOF and its metabolite and VEL ;Timepoint(s) of evaluation of this end point: • SVR 4 and 24 weeks • PK Day 7 | — |
Countries
Australia, Canada, Israel, New Zealand, Spain, United Kingdom
Contacts
Public ContactClinical Trials Mailbox
Gilead Sciences International Ltd.
Outcome results
None listed