Open-Label Safety Study of Telaprevir and Sofosbuvir in Chronic Hepatitis C Genotype 1

Study Overview
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Brief Summary
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This is an open-label, multi center study of treatment-naive non-cirrhotic subjects with genotype 1 chronic Hepatitis C Virus. All subjects will receive telaprevir (TVR) in combination with sofosbuvir (SOF) for 12 weeks.

Detailed Description
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Starting on Day 1 and for up to 12 weeks, you will receive Telaprevir (TVR) and Sofosbuvir (SOF). You will take one (1) 400 mg tablet of SOF and 3 tablets (1125 mg each) of TVR. You should take these together by mouth every morning. You will take another 3 tablets (1125 mg each) of TVR by mouth 12 hours after you take your morning dose.

Official Title
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Open-Label Study to Evaluate the Safety and Tolerability of Telaprevir in Combination With Sofosbuvir in Treatment Naive Subjects Chronically Infected With Hepatitis C Virus Genotype 1

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Telaprevir and Sofosbuvir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide informed consent BMI (Body Mass Index) ≥ 18 kg/m2 HCV RNA quantifiable at screening and >1,000 IU/ml HCV treatment Naïve HCV genotype 1 7. Confirmation of chronic HCV infection documented by either: A positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit, or A liver biopsy performed prior to the Baseline/Day 1 visit with evidence of chronic HCV infection Exclusion Criteria: Current or prior history of any of the following: Clinically-significant illness Cirrhosis 2. Screening ECG with clinically significant abnormalities ALT > 10 x the upper limit of normal (ULN) AST > 10 x ULN Direct bilirubin > 1.5 x ULN Platelets < 150,000/μL HbA1c > 7.5% Creatinine clearance (CLcr) < 60 mL /min, as calculated by the Cockcroft-Gault equation Hemoglobin < 11 g/dL for female subjects; < 12 g/dL for male subjects. Albumin < 3.1 g/dL INR > 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR 4. Prior exposure to any approved or experimental HCV-specific direct-acting 5. Pregnant or nursing female or male with pregnant female partner. 6. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, alfa-1 antitrypsin deficiency, cholangitis). 7. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV).

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telaprevir and Sofosbuvir<br>All subjects will receive Telaprevir twice a day, 1125mg capsule and Sofosbuvir 400 mg capsule once daily. Both will be given for 12 weeks. | Drug: Telaprevir and Sofosbuvir<br>* All subjects will have time to read and discuss IRB approved consent form prior to any study procedures. Following proper consenting, subjects will undergo physical exam including ECG and bloodwork prior to baseline visit. Subjects will return for research visits (vitals, collection of AEs, bloodwork, drug accountability) on Day 3, Weeks 1, 2, 3, 4, 6, 8, 10 and 12 of treatment and 4, 12, and 24 weeks after end of treatment. PK samples will be collected at week 2 and week 10.<br>* Other names: SOF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Adverse Events Leading to Discontinuation of Both Telaprevir and Sofosbuvir Among Subjects Treated With Telaprevir and Sofosbuvir | Study drug adherence and adverse events were collected on all enrolled subjects and graded using the DAIDS scale. Any adverse events leading to discontinuation of both Telaprevir and Sofosbuvir were collected and are hereby reported. | 12 weeks-January 3, 2014- April 10, 2014 | 
| Safety of Telaprevir and Sofosbuvir When Dosed in Combination for 12 Weeks | The number of subjects who experienced Grade 3 anemia. Complete blood count was collected at baseline, week 2, week 4, week 8, week 12, week 18, and week 24. Incidence of moderate anemia (Grade 3) observed in the study treatment period. | 1/3/2014-4/10/2014 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize Steady State of Sofosbuvir Active SOF Metabolite, GS-331007 | Sparse Pharmokinetic blood samples were collected at Week 2 and Week 10 (prior to daily dose) in patients treated with Telaprevir and Sofosbuvir. | 1/17/2014-3/26/2014 | 
| Proportion of Subjects Who Achieve Undetectable Hepatitis C Virus RNA at 12 Weeks After Completing Study Drug Regimen | Plasma HCV RNA levels were assessed using the COBAS TaqMan HCV RNA assay test (v2.0; Roche Diagnostics, Indianapolis, IN, USA; LLOQ=25 IU/mL;limit of detection =15 IU/mL) | 6/16/2014-7/2/2014 | 
| Proportion of Subjects With Viral Relapse | Defined as Subjects who have undetectable HCV RNA at end of treatment, and confirmed detectable HCV RNA between end of treatment and SVR12 planned assessment time point. | 1/3/2014-9/8/2014 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV Genotype 1, Hepatitis C Virus Genotype 1, HCV, TVR