A Safety and Efficacy Study of the Combination of VX-222 and Telaprevir in Treatment-Naïve Subjects With Genotype 1 Chronic Hepatitis C Virus Infection

Sponsor

Vertex Pharmaceuticals Incorporated (Industry)

Overall Status

Terminated

CT.gov ID

NCT01080222

Collaborator

(none)

152

Enrollment

Locations

Arms

Duration (Months)

7.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and efficacy of combination treatment with VX-222 and telaprevir administered for 12 weeks with and without peginterferon-alfa-2a and/or ribavirin. The subjects enrolled in this study are chronically infected with hepatitis C virus (HCV) genotype 1 and will not have previously received treatment for their HCV infection.

This study will include an Investigational Phase and Extension Phase. These phases will contain a Treatment Period and a Follow-up Period. All subjects will be enrolled in the Investigational Phase of this study. Subjects who fail treatment during the Investigational Phase will have the option to enter the Extension Phase at which point they will be eligible to receive peginterferon alfa-2a and ribavirin for a total of 48 weeks.

Based on an evaluation of on-treatment safety, pharmacokinetic and antiviral data from patients in each arm of the trial, Vertex may elect to enroll up to two additional treatment arms (Treatment Arm E and Treatment Arm F) that will evaluate telaprevir/VX-222-based combination therapy. The components of the treatment regimens of these arms will be selected based on clinical data that emerges from the four initially-studied regimens. If enacted, up to 25 patients are expected to enroll in each additional treatment arm.

If Treatment Arm E or Treatment Arm F is discontinued subjects meeting certain criteria will have the option to enter a telaprevir-containing Rollover Phase. Subjects who do not meet the eligibility criteria to enter the Rollover Phase may elect to enter the Extension Phase.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Virus Infection	Drug: telaprevir Drug: VX-222 Drug: ribavirin Biological: peginterferon-alfa-2a Drug: VX-222	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

152 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Parallel-Group, Dose-Ranging Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Antiviral Activity of VX-222 and Telaprevir in Combination With and Without Peginterferon-Alfa-2a (Pegasys®) and Ribavirin (Copegus®) in Treatment-Naïve Subjects With Genotype 1 Chronic Hepatitis C

Study Start Date :

Aug 1, 2010

Actual Primary Completion Date :

Oct 1, 2013

Actual Study Completion Date :

Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm A Treatment Arm A was discontinued as a result of patients meeting a pre-defined stopping rule related to viral breakthrough during the first four weeks of dosing.	Drug: telaprevir tablet, 1125-mg, twice daily Drug: VX-222 capsule, 100-mg, twice daily
Experimental: Treatment Arm B Treatment Arm B was discontinued as a result of patients meeting a pre-defined stopping rule relating to viral breakthrough.	Drug: telaprevir tablet, 1125-mg, twice daily Drug: VX-222 capsule, 400-mg, twice daily
Experimental: Treatment Arm C Subjects who meet pre-specified viral response criteria will stop their assigned treatment at 12 weeks. Subjects who do not meet the pre-specified viral response criteria will receive peginterferon alfa-2a and ribavirin for an additional 12 weeks for a total treatment duration of 24 weeks. Enrollment for this arm is complete. No additional subjects will be recruited.	Drug: telaprevir tablet, 1125-mg, twice daily Drug: VX-222 capsule, 100-mg, twice daily Drug: ribavirin tablet, 1000-mg for subjects weighing <75-kg or 1200-mg for subjects weighing ≥75-kg, twice daily Biological: peginterferon-alfa-2a subcutaneous injection, 180-mcg, once weekly
Experimental: Treatment Arm D Subjects who meet pre-specified viral response criteria will stop their assigned treatment at 12 weeks. Subjects who do not meet the pre-specified viral response criteria will receive peginterferon alfa-2a and ribavirin for an additional 12 weeks for a total treatment duration of 24 weeks. Enrollment for this arm is complete. No additional subjects will be recruited.	Drug: telaprevir tablet, 1125-mg, twice daily Drug: ribavirin tablet, 1000-mg for subjects weighing <75-kg or 1200-mg for subjects weighing ≥75-kg, twice daily Biological: peginterferon-alfa-2a subcutaneous injection, 180-mcg, once weekly Drug: VX-222 capsule, 400-mg, twice daily
Experimental: Treatment Arm E Subjects who meet pre-specified viral response criteria will stop their assigned treatment at 12 weeks. Subjects who do not meet the pre-specified viral response criteria will receive peginterferon alfa-2a and ribavirin for an additional 24 weeks for a total treatment duration of 36 weeks.	Drug: telaprevir tablet, 1125-mg, twice daily Drug: ribavirin tablet, 1000-mg for subjects weighing <75-kg or 1200-mg for subjects weighing ≥75-kg, twice daily Drug: VX-222 capsule, 400-mg, twice daily
Experimental: Treatment Arm F Subjects who meet pre-specified viral response criteria will stop their assigned treatment at 12 weeks. Subjects who do not meet the pre-specified viral response criteria will receive peginterferon alfa-2a and ribavirin for an additional 24 weeks for a total treatment duration of 36 weeks.	Drug: telaprevir tablet, 1125-mg, twice daily Drug: ribavirin tablet, 1000-mg for subjects weighing <75-kg or 1200-mg for subjects weighing ≥75-kg, twice daily Drug: VX-222 capsule, 400-mg, twice daily

Outcome Measures

Primary Outcome Measures

Safety and Tolerability [40 weeks]
Assessed by adverse events, physical examinations, vital signs, 12 lead electrocardiograms (ECGs), and laboratory assessments (serum chemistry, hematology, and urinalysis) vital signs, 12-lead electrocardiograms (ECGs), and laboratory assessments (clinical chemistry, hematology, and urinalysis)

Secondary Outcome Measures

Proportion of Subjects Who Achieve a Sustained Viral Response [24 weeks after the completion of the last dose of the assigned study drug treatment regimen]
Undetectable HCV RNA Measurements [36 weeks]
Time to undetectability Proportion of subjects who achieve undetectable HCV RNA levels at Week 2, Week 4, Week 8, and Week 12 Proportion of subjects who achieve undetectable HCV RNA levels at Week 2 and Week 8 Proportion of subjects who have undetectable HCV RNA levels at the end of treatment
Proportion of Subjects Who Have a Viral Breakthrough or Relapse [60 weeks]
Plasma Exposures of VX-222 and Telaprevir [12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males and females of non-childbearing potential
Genotype 1 chronic hepatitis C
Laboratory evidence of HCV infection for 6 months
Histologic evidence of chronic hepatitis C
Subjects who have a body mass index (BMI) of ≤35 kg/m² (BMI = weight in kg / height² in meters)
Treatment Arm E: This arm will enroll only subjects infected with HCV genotype 1b virus
Treatment Arm F: This arm will enroll only subjects infected with HCV genotype 1a virus

Exclusion Criteria:

Subjects who have received any previous treatment with any approved or investigational drug or drug regimen for the treatment of hepatitis C
Subjects with any contraindications to peginterferon alfa-2a and/or ribavirin
Subjects with any other cause of significant liver disease in addition to hepatitis C, which may include, but is not limited to malignancy with hepatic involvement, hepatitis B, drug or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, nonalcoholic steatohepatitis (NASH), or primary biliary cirrhosis
Histologic evidence of hepatic cirrhosis

Contacts and Locations

Locations

	City	State	Country
1	La Jolla	California	United States
2	San Francisco	California	United States
3	Aurora	Colorado	United States
4	Gainesville	Florida	United States
5	Atlanta	Georgia	United States
6	Marietta	Georgia	United States
7	Lutherville	Maryland	United States
8	Rochester	Minnesota	United States
9	Saint Louis	Missouri	United States
10	Egg Harbor Township	New Jersey	United States
11	New York	New York	United States
12	Chapel Hill	North Carolina	United States
13	Durham	North Carolina	United States
14	Cincinnati	Ohio	United States
15	Providence	Rhode Island	United States
16	Germantown	Tennessee	United States
17	Arlington	Texas	United States
18	San Antonio	Texas	United States
19	Falls Church	Virginia	United States
20	Auckland		New Zealand
21	Christchurch		New Zealand