| Eligibility |
- INCLUSION CRITERIA:
Phase I Treatment
- Male or female >= 18 years of age
- Either treatment naive or experienced defined as failure of a prior course of
interferon-based and ribavirin, DAA plus interferon and DAA only
- Confirmation of chronic HCV infection documented by:
- A positive HCV RNA or positive HCV genotyping test at least 6-months prior to the
Baseline/Day 1 visit
- A liver biopsy performed prior to screening visit showing evidence of chronic
hepatitis.
- Subjects must have the following laboratory parameters at screening:
- ALT <= 10 x the upper limit of normal (ULN)
- AST <= 10 x ULN
- Total bilirubin <2.5 mg/dL, Direct bilirubin <= 1.5 ULN
- Platelets >= 50,000 K/mm^3
- HbA1c <= 8.5%
- Hemoglobin >= 10g/dL
- Albumin >= 3g/dL
- INR <= 1.5 unless subject has known hemophilia or is stable on an anticoagulant
regimen affecting INR.
- HCV RNA positive at screening.
- Subjects must be of generally good health, with the exception of chronic HCV
infection, as determined by the Investigator.
Phase II Follow-up
- Male or female >= 18 years of age.
- SVR24 following therapy with a direct acting antiviral agent regimen and available
liver biopsy performed prior to treatment.
- Subject must be of generally good health as determined by the Investigator.
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation
in this study:
Phase I Treatment
- Pregnancy or lactation
- Inability to practice one form of adequate contraction for females of childbearing
potential
- Prior treatment with a NS5a agent
- Current or prior history of any of the following:
- Clinically significant illness (other than HCV) or any other major medical
disorder that may interfere with subject treatment, assessment, or compliance
with the protocol; subjects currently under evaluation for a potentially
clinically significant illness (other than HCV) are also excluded
- Gastrointestinal disorder or post-operative condition that could interfere with
the absorption of the study drug
- Decompensated liver disease as defined by serum bilirubin >= 2.5 mg/dL (with
direct bilirubin >= 1.5 mg/dL), INR >1.5 a serum albumin of less than 3 g/dL, or
a history of ascites, hepatorenal syndrome, variceal bleeding, or hepatic
encephalopathy
- Solid organ transplantation
- Significant pulmonary disease, significant cardiac disease
- History of malignancy or treatment for a malignancy within the past 3 years that is
associated with a life expectancy <5 years (except adequately treated carcinoma in
situ or basal cell carcinoma of the skin).
- Chronic liver disease of a non-HCV etiology with the exception of steatosis (e.g.,
chronic hepatitis B, hemochromatosis, Wilson s disease, alfa-1 antitrypsin deficiency,
cholangitis).
- Evidence of harmful or hazardous drinking as defined as a score >= 8 on the AUDIT
questionnaire.
- Co-infection with HIV defined as the presence of anti-HIV in serum.
- Clinically relevant drug abuse based on patient history within 12 months of screening.
- Use of medications contraindicated with use of sofosbuvir/velpatasvir within 21 days
of the Baseline/Day 1 visit; this washout period does not apply to proton pump
inhibitors, which can be taken up to 7 days before baseline Day 1 for the following:
- Acid reducing Agents
- Antiarrhythmics
- Anticancer
- Antimycobacterial
- HIV antivirals
- Herbal supplements
- HMG-CoA Reductase Inhibitors
- Use of antiviral medications within the last 30 days.
- Chronic use of systemically administered immunosuppressive agents (e.g., prednisone
equivalent >= 10 mg/day).
- Known hypersensitivity to sofosbuvir and velpatasvir, or formulation excipients.
- Hepatocellular carcinoma, or the presence of a mass on imaging studies of the liver
that is suggestive of hepatocellular carcinoma, or an alpha-fetoprotein level of
greater than 500 mg/mL
- Active psychiatric problems such as major depression, schizophrenia, bipolar illness,
obsessive-compulsive disorder, severe anxiety, or personality disorder that, in the
investigator s opinion, might interfere with participation in the study.
- Presence of conditions that, in the opinion of the investigators, would not allow the
subject to n the current study for at least 1 year.
Phase II Follow-up
- Pregnancy
- Current or prior history of any of the following:
- Clinically significant illness (other than resolved HCV) or any other major
medical disorder that may interfere with subject treatment, assessment, or
compliance with the protocol; subjects currently under evaluation for a
potentially clinically significant illness
(other than HCV) are also excluded
--Decompensated liver disease as defined by serum bilirubin >= 2.5 mg/dL (with direct
bilirubin >= 1.5 mg/dL), INR >1.5 a serum albumin of less than 3 g/dL, or a history of
ascites, hepatorenal syndrome, variceal bleeding, or hepatic encephalopathy.
- Solid organ transplantation
- Significant pulmonary disease, significant cardiac disease
- History of malignancy or treatment for a malignancy within the past 3 years that
is associated with a life expectancy <5 years (except adequately treated
carcinoma in situ or basal cell carcinoma of the skin)
- Chronic liver disease with the exception of steatosis (e.g., chronic hepatitis B,
hemochromatosis, Wilson s disease, alfa-1 antitrypsin deficiency, cholangitis)
- Evidence of harmful or hazardous drinking as defined as a score >= 8 on the AUDIT
questionnaire
- Co-infection with HIV defined as the presence of anti-HIV in serum
- Clinically relevant drug abuse based on patient history within 12 months of
screening
- Chronic use of systemically administered immunosuppressive agents (e.g.,
prednisone equivalent >= 10 mg/day)
- Hepatocellular carcinoma, or the presence of a mass on imaging studies of the
liver that is suggestive of hepatocellular carcinoma, or an alpha-fetoprotein
level of greater than 500 mg/mL
- Active psychiatric problems such as major depression, schizophrenia, bipolar
illness, obsessive-compulsive disorder, severe anxiety, or personality disorder
that, in the investigator s opinion, might interfere with participation in the
study
- Presence of conditions that, in the opinion of the investigators, would not allow
the patient to be followed in the current study for at least 1 year.
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