People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents

This is an interventional treatment trial for Diabetes Mellitus focused on measuring Natural History, Hepatitis C Virus, Hepatocellular Carcinoma, Fibrosis, Immune Response Read More

• 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/mm3
  • 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.