Long-Term Follow-Up Of Subjects With CHC Who Achieved A Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 121
- 试验地点
- 1
- 主要终点
- Phase II: Liver-related clinical outcome, HCC, or liver-related mortality
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Phase II after Phase I
Participants who achieved SVR12 in Phase I
Phase I
Phase I treatment
干预措施: Epclusa (Drug)
Phase II without Phase I
Participants who achieved SVR 24 previously
结局指标
主要结局
Phase II: Liver-related clinical outcome, HCC, or liver-related mortality
时间窗: 480 Weeks
Composite of ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma, liver-related mortality
Phase I - SVR 12
时间窗: 24 weeks
SVR at 12 weeks after completion of 12 weeks of treatment
次要结局
- Phase II: HCC(480 weeks)
- Phase II: Change in Fibroscan(480 weeks)
- Phase II: Assess Regression in Portal Hypertension(480 weeks)
- Phase II: Change in Ishak fibrosis score(480 weeks)
- Phase II: All-cause mortality(480 weeks)