Hepatitis C Virus(HCV) Heart and Lung Study

Study Overview
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Brief Summary
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This is a multicenter study in Hepatitis C Virus (HCV) infected adult patients who also have advanced cardiac disease or advanced lung disease.

Detailed Description
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This is a multicenter study in HCV infected adult patients who also have either advanced cardiac disease, or advanced lung disease. Advanced cardiac disease is defined as a marked limitation of physical activity, or discomfort upon physical activity. The patients in the advanced cardiac disease group must also have been hospitalized for heart failure within the last 12 months. Advanced lung disease is defined as patients who have been diagnosed with chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD). Patients in the COPD group must have abnormalities in their forced expiratory volume (FEV) test, which measures the amount of air exhaled. They may or may not need supplemental oxygen. Patients in the ILD group must have been diagnosed with ILD and require supplement oxygen at all times.

Official Title
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A Multicenter, Open-label Study of Harvoni ® (Sofosbuvir Ledipasvir Fixed Dose Combination) in Subjects Infected With Chronic Hepatitis C and Advanced Heart Failure or Lung Disease

Conditions
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Lung Diseases, Interstitial, Hepatitis C, Chronic, Heart Failure, Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic HCV Infection of Genotype 1, 4, 5, or 6 HCV RNA > 103 IU/mL at screening 18 years of age or older Diagnosis of chronic HCV infection, defined as positive HCV antibody or HCV RNA more than 6 months prior to screening OR an assessment of fibrosis F2 or greater prior to screening. Subjects in the advanced heart failure cohort must meet all HCV criteria, and all of the following criteria: New York Heart Association (NYHA) Class III or IV functional classification NYHA Class III: Subjects with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain. NYHA Class IV: Patient with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased. ejection fraction ≤ 30% hospitalized for heart failure in last 12 months Subjects in the advanced lung disease cohort must have been diagnosed with chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD) must meet all HCV criteria, and meet the following criteria for COPD or ILD: ILD criteria: diagnosis of interstitial lung disease with chronic supplemental oxygen requirement at rest and/or with exertion. COPD criteria (one of the following): Forced expiratory volume (FEV1)< 30% predicted OR any FEV1 with chronic supplemental oxygen requirement at rest and/or with exertion OR any FEV1 with chronic hypercapnia (baseline partial pressure of arterial carbon dioxide [PaCO2] > 45) Exclusion Criteria: Chronic HCV Infection with Genotype 2 or 3 Treatment with any of the following agents Amiodarone. Subjects previously treated with amiodarone must have stopped the amiodarone at least 60 days prior to day 1 of SOF/LDV FDC Carbamazepine, phenytoin, phenobarbital, oxcarbazepine Rifabutin, rifampin or rifapentine HIV regimens containing tenofovir or tipranavir/ritonavir St. John's wort Rosuvastatin Have any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment, or compliance History of hepatic encephalopathy or variceal hemorrhage Hepatitis B surface antigen positive Abnormal hematological and biochemical parameters, including: Hemoglobin (Hb) < 8 g/dL Platelets ≤ 50,000/mm3 alanine aminotransferase (ALT), aspartase aminotransferase (AST), or alkaline phosphatase ≥ 10 times upper limit of normal(ULN) Total bilirubin > 3 mg/dl Severe renal impairment creatinine clearance (CrCl), i.e. < 30 mL/min. History of major organ transplantation with an existing functional graft. History of clinically-significant drug allergy to nucleoside/nucleotide analogs. Pregnant women or women planning to become pregnant Women who are breastfeeding Active or recent history (≤ 1 year) of drug or alcohol abuse

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Heart Failure Cohort<br>Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir (SOF) and 90 mg ledipasvir (LDV) | Drug: Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC)<br>* 1 pill once daily of SOF/LDV FDC<br>* Other names: Harvoni;|
| Experimental: Lung Disease Cohort<br>Harvoni (sofosbuvir/ledipasvir fixed dose combination) 1 pill once daily Includes 400 mg sofosbuvir and 90 mg ledipasvir | Drug: Sofosbuvir/ledipasvir fixed dose combination(SOF/LDV FDC)<br>* 1 pill once daily of SOF/LDV FDC<br>* Other names: Harvoni;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Completed 24 Weeks of Therapy | The primary safety endpoint is the number of subjects who complete a full course of therapy. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Sustained Virologic Response (SVR) 12 | The secondary outcome of efficacy will be determined by the number of subjects with hepatitis c virus ribonucleic acid (HCV RNA) below a measurable laboratory limit, 12 weeks after completing therapy. | 12 weeks after completing treatment | 
| Number of Subjects With Sustained Virologic Response (SVR) 4 | The secondary outcome of efficacy will be determined by the number of subjects with hepatitis c virus ribonucleic acid (HCV RNA) below a measurable laboratory limit, 4 weeks after completing treatment. | 4 weeks after completing treatment |