Diabetes MellitusPhase 4NCT03520660

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

A Phase 4 study testing Epclusa in people with Diabetes Mellitus and Hepatitis C, Chronic, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Background: 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. Read more about this study

Who is it for?: Ages 18 to 120 years
Conditions the study is for: Diabetes Mellitus, Hepatitis C, Chronic, Cardiovascular Diseases
What is being tested?: Epclusa
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 121 participants
Where: 1 siteUnited States
Study dates: 19 Oct 2018to 31 Dec 2032
Phase: Phase 4

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 120 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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.

Who cannot join

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:

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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.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Long-Term Follow-Up Of Subjects With CHC Who Achieved A Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents

Background:

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

Questionnaires

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.

Read the detailed description

Study Description:<TAB>

We intend to enroll up to 350 subjects with chronic hepatitis C virus (HCV) infection. Subjects will be recruited from two sources:

Phase I: treatment na(SqrRoot) ve or experienced who have failed a prior treatment (including DAA-experienced) who are willing to undergo a pre-treatment liver biopsy.
Subjects yet to achieve an SVR will receive 12 weeks of therapy with sofosbuvir/velapatasvir (Epclusa(R)) fixed dose combination
Subjects yet to achieve SVR with evidence of clinical cirrhosis will undergo a transjugular liver biopsy with hepatic venous portal gradient (HVPG) pressure measurements in lieu of the percutaneous liver biopsy
Phase II: subjects who have already achieved sustained virologic response (SVR) with oral direct-acting antiviral agent (DAA) only regimen and who have undergone a liver biopsy prior to therapy and no history of hepatic decompensation or hepatocellular carcinoma. Subjects who have attained an SVR prior to enrollment (or upon achieving an SVR12 and SVR24 in Phase I) will undergo a thorough medical evaluation:

laboratory testing
Fibroscan(R)
hepatic ultrasound Thereafter, subjects will be followed prospectively every 24 weeks for liver decompensation (ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage), hepatocellular carcinoma, liver-related mortality, and all-cause mortality. During each study visit, subjects will be questioned on the development of these adverse outcomes. In addition, blood will be drawn for the assessment of routine blood tests, quantitative viral biomarker levels, serological response markers and immune cell functional status. Blood, urine, and stool will be collected and stored for exploratory biomarker development. Fibroscan(R) will be performed annually in all subjects. For subjects with cirrhosis, esophagogastroduodenoscopy (EGD) will be performed annually and imaging every 24 weeks. At the end of 240 weeks, all subjects will be admitted for a liver biopsy to assess the stage of liver fibrosis. In subjects with cirrhosis at study entry, the liver biopsy will be performed by the transjugular route with hepatic venous portal gradient (HVPG) pressure measurements. The primary goal of the study will be to describe the outcome of viral eradication following treatment with direct acting antiviral agents, to identify predictors of adverse outcomes after sustained viral eradication and regression of fibrosis/cirrhosis. Objectives: Primary Objective:
Phase 1: SVR12 and SVR24
Phase II: The rate of clinical outcomes (ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage), hepatocellular carcinoma, liver-related mortality, and all-cause mortality Secondary Objectives:
Phase II: The proportion and rates of fibrosis regression in subjects
Phase II: The agreement between Fibroscan and Ishak fibrosis score
Phase II: The comparison of change in Fibroscan and change in Ishak fibrosis as predictors of the primary outcome.
Phase II: To assess regression of portal hypertension in subjects with pre-existing portal hypertension either confirmed by direct portal pressure measurement, indirectly by hepatic venous pressure gradient or clinical evidence of portal hypertension such as presence of esophageal or gastric varices of portal hypertensive gastropathy and all-cause mortality. Exploratory Objective:
To develop novel biomarkers and genetic predictors of liver-related complications including hepatocellular carcinoma.
To assess outcome of HCV-related immune dysfunction following sustained eradication of HCV.
To assess changes in antibody titer and breadth, B cell activation, and T cell memory after sustained HCV eradication.
To prospectively assess the rate of non-hepatic outcomes (diabetes, cardiovascular and renal disease, malignancy including lymphoma, and health related quality of life) following SVR with DAA agents.
To characterize the changes in serum lipids and lipoproteins during and after therapy with direct acting antiviral agents and assess cardiovascular risk following eradication of HCV based on serum/plasma LDL particle number. Endpoints: Primary Endpoint:
SVR at 12 weeks after completion of 12 weeks of treatment.
Composite of ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma, liver-related mortality, and all-cause mortality at 480 weeks. Secondary Endpoints:
Improvement in semi-quantitative Ishak fibrosis score after HCV clearance.
Correlation between Fibroscan (transient elastography) with Ishak fibrosis score after HCV clearance.
Does change improvement in Fibroscan and change in Ishak fibrosis correlate with clinical outcome.
Change in portal pressure after SVR12.

Conditions: Diabetes Mellitus, Hepatitis C, Chronic, Cardiovascular Diseases
Being tested: Epclusa
Keywords: Natural History, Hepatitis C Virus, Hepatocellular Carcinoma, Fibrosis, Immune Response
Medical subject headings: Diabetes Mellitus, Hepatitis C, Chronic, Cardiovascular Diseases, Hepatitis C, Carcinoma, Hepatocellular, Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EpclusaDrug
sofosbuvir/velapatasvir combination (Epclusa)

Study groups in NCT03520660
Study group	Role	What they receive
Phase I	Experimental	Phase I treatment Receives: Drug: Epclusa
Phase II after Phase I	No intervention	Participants who achieved SVR12 in Phase I
Phase II without Phase I	No intervention	Participants who achieved SVR 24 previously

What is being measured

The primary outcome is the main question the study is designed to answer.

Phase II: Liver-related clinical outcome, HCC, or liver-related mortality
Composite of ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma, liver-related mortality
Measured: 480 Weeks
Phase I - SVR 12
SVR at 12 weeks after completion of 12 weeks of treatment
Measured: 24 weeks

Secondary outcomes (5)

Phase II: All-cause mortality
Measured: 480 weeks
Phase II: Change in Fibroscan
Measured: 480 weeks
Phase II: Assess Regression in Portal Hypertension
Measured: 480 weeks
Phase II: HCC
Measured: 480 weeks
Phase II: Change in Ishak fibrosis score
Measured: 480 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Oct 201831 Dec 2032

First posted11 May 2018
Study start19 Oct 2018
Primary completion31 Dec 2032 (estimated)
Study completion31 Dec 2032 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Diabetes MellitusStudies of the same condition, open and under way.
More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 121 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03520660
Sponsor's protocol ID: 180091
Other IDs: 18-DK-0091
Status last verified: 20 Oct 2026
First submitted: 9 May 2018
Last updated: 22 Oct 2026
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No