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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: Telaprevir and Sofosbuvir

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • UF Hepatology Research at CTRB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

1. ALT > 10 x the upper limit of normal (ULN)
2. AST > 10 x ULN
3. Direct bilirubin > 1.5 x ULN
4. Platelets < 150,000/μL
5. HbA1c > 7.5%
6. Creatinine clearance (CLcr) < 60 mL /min, as calculated by the Cockcroft-Gault equation
7. Hemoglobin < 11 g/dL for female subjects; < 12 g/dL for male subjects.
8. Albumin < 3.1 g/dL

9. 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Telaprevir and Sofosbuvir; 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; 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.; Other Names: SOF; TVR

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Sustained Virologic Response at 4 Weeks After Completion of Last Dose	Subjects who complete assigned treatment and have undetectable HCV RNA at 12 weeks after the last planned dose of study treatment	4/22/2014-5/6/2014

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Vertex Pharmaceuticals Incorporated
• Investigators: Study Director: DAVID R NELSON, MD, University of Florida

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: November 12, 2013
• First Submitted That Met QC Criteria: November 19, 2013
• First Posted (Estimate): November 25, 2013

Study Record Updates

• Last Update Posted (Actual): April 23, 2018
• Last Update Submitted That Met QC Criteria: March 21, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: HCV; HCV Genotype 1; Hepatitis C Virus Genotype 1; TVR
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Anti-Infective Agents; Antiviral Agents; Sofosbuvir
• Other Study ID Numbers: 20132125