This study is NOT currently recruiting participants.
Number
18-DK-0091
Sponsoring Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Recruitment Detail
Type: No longer recruiting/follow-up only Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Pregnant Women;Children
Keywords
Natural History; Hepatitis C Virus; Hepatocellular Carcinoma; Fibrosis; Immune Response
Recruitment Keyword(s)
None
Condition(s)
Diabetes Mellitus; Hepatitis C, Chronic; Cardiovascular Diseases
Investigational Drug(s)
Investigational Device(s)
Intervention(s)
Drug: Epclusa
Supporting Site
National Institute of Diabetes and Digestive and Kidney Diseases
Chronic hepatitis C infects the liver. It may scar the liver. This is called cirrhosis and may lead to liver cancer or death. Current chronic hepatitis C treatments cure most people. But some keep getting complications even after it is cured. Researchers want to study why.
Objective:
To study the course and complications of liver disease after cure of hepatitis C infection.
Eligibility:
Adults 18 years and older infected with chronic hepatitis C virus who were never treated or were treated and not cured and those who were cured
Design:
Participants will be screened with:
Blood and urine tests
Questionnaires
Liver ultrasound
Fibroscan. A probe vibrates the liver, testing stiffness.
In Phase 1, people with chronic hepatitis C will:
Have a 3-day hospital admission to repeat some screening tests and have a liver biopsy. A small piece of liver is removed by needle passed through the skin.
Take 1 tablet containing 2 hepatitis C drugs once a day for 12 weeks.
Repeat some blood tests at 3 visits in those 12 weeks while on treatment, then 4 additional visits in the next 24 weeks with more blood work collected.
Phase 1 participants who test negative for hepatitis C and all other eligible participants will enter Phase 2.
Phase 2 participants will have a visit every 24 weeks for 10 years. These may include:
Repeats of screening tests
Scans
Stool tests
Chest x-ray
Heart function test
Endoscopy. A tube guides a camera into the upper digestive system.
At about 5 years, participants will have another liver biopsy.
Some participants will give separate consent for genetic testing and a special blood procedure.
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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.
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:
-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.
-Pregnancy
--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.
-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)
-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.
Principal Investigator
Referral Contact
For more information: