A Study to Evaluate the Efficacy and Safety of Quadruple Therapy (VX-222, Telaprevir,Peginterferon-Alfa-2a, Ribavirin) in Subjects With Chronic Hepatitis C With Compensated Cirrhosis

Sponsor

Vertex Pharmaceuticals Incorporated (Industry)

Overall Status

Completed

CT.gov ID

NCT01516918

Collaborator

(none)

103

Enrollment

Locations

Arm

Duration (Months)

2.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of a quadruple regimen (VX-222, telaprevir, pegylated interferon, and ribavirin)in subjects with hepatitis C with cirrhosis.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

103 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Open-Label Phase 2b Pilot Study to Evaluate the Efficacy and Safety of Quadruple Therapy (VX-222, Telaprevir, Peginterferon-Alfa-2, and Ribavirin) in Subjects With Genotype 1 Chronic Hepatitis C With Compensated Cirrhosis

Study Start Date :

Feb 1, 2012

Actual Primary Completion Date :

Sep 1, 2013

Actual Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Quadruple Regimen All subjects will receive active study drugs (quadruple regimen: VX-222, telaprevir,Peg-IFN, and RBV) for a fixed treatment duration of 24 weeks.	Drug: VX-222 tablet, 400-mg twice daily Drug: telaprevir tablet, 1125-mg twice daily Other Names: Incivek, VX-950, Incivo Drug: ribavirin tablet, 1000-mg per day for subjects weighing <75 kg and 1200 mg per day for subjects weighing ≥75 kg, twice daily Other Names: Copegus Biological: peginterferon-alfa-2a subcutaneous injection, 180-mcg, once weekly Other Names: Pegasys

Arm

Intervention/Treatment

Experimental: Quadruple Regimen

All subjects will receive active study drugs (quadruple regimen: VX-222, telaprevir,Peg-IFN, and RBV) for a fixed treatment duration of 24 weeks.

Drug: VX-222

tablet, 400-mg twice daily

Drug: telaprevir

tablet, 1125-mg twice daily

Other Names:

Incivek, VX-950, Incivo

Drug: ribavirin

tablet, 1000-mg per day for subjects weighing <75 kg and 1200 mg per day for subjects weighing ≥75 kg, twice daily

Other Names:

Copegus

Biological: peginterferon-alfa-2a

subcutaneous injection, 180-mcg, once weekly

Other Names:

Pegasys

Outcome Measures

Primary Outcome Measures

The proportion of subjects who have a sustained virologic response at 12 weeks after the last planned dose of treatment (SVR12) [12 weeks]

Secondary Outcome Measures

The safety and tolerability as assessed by adverse events, vital signs, 12-lead electrocardiograms and laboratory assessments. [up to 48 weeks]
The proportion of subjects who have an SVR 24 weeks after the last planned dose of the study drug (SVR24) [24 weeks]
The proportion of subjects who achieve undetectable HCV RNA at Weeks 2, 4, 8, and 12 after the first dose of study drug, and at the end of planned study drug treatment [up to week 12]
The proportion of subjects who have on-treatment virologic failure defined as subjects who either meet a futility rule or who complete the assigned treatment duration and have HCV RNA at the end of study drug treatment [up to 48 weeks]
The association of the IL-28B genotype with SVR12 [12 weeks]
Proportion of subjects who have SVR12 by IL-28B genotype
The amino acid sequence of the nonstructural (NS)3 and NS5B proteins in subjects who have treatment failure [After the last planned dose of study drug or after time of failure]
The identity and observed frequency of viral variants as compared to wild-type virus will be measured.
VX-222, telaprevir, and RBV plasma concentrations and Peg-IFN serum concentrations [12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects must have genotype 1 Chronic Hepatitis C
Subjects must have compensated cirrhosis
Subjects may either be treatment naïve, or may have received a course of Peg IFN/RBV without evidence of response. Subjects who are considered to be relapsers to Peg IFN/RBV, or who are partial or null responders will be considered
Subjects with hemophilia may be permitted to enroll with permission of the medical monitor

Exclusion Criteria:

Any previous treatment with an investigational drug or drug regimen for the treatment of hepatitis C, or previous treatment with an approved protease inhibitor
Any contraindication to Peg-IFN or RBV therapy
Evidence of hepatic decompensation: history of ascites, hepatic encephalopathy, or bleeding esophageal varices
A history of acquired immunodeficiency infection, organ transplantation or have an ongoing requirement for immunosuppressive medicines

Contacts and Locations

Locations

	City	State	Country
1	Birmingham	Alabama	United States
2	San Diego	California	United States
3	Englewood	Colorado	United States
4	Bradenton	Florida	United States
5	Jacksonville	Florida	United States
6	Tampa	Florida	United States
7	Marietta	Georgia	United States
8	Chicago	Illinois	United States
9	Indianapolis	Indiana	United States
10	Boston	Massachusetts	United States
11	Detroit	Michigan	United States
12	Lebanon	New Hampshire	United States
13	Egg Harbor Township	New Jersey	United States
14	Manhasset	New York	United States
15	New York	New York	United States
16	Rochester	New York	United States
17	Asheville	North Carolina	United States
18	Charlotte	North Carolina	United States
19	Durham	North Carolina	United States
20	Cincinnati	Ohio	United States
21	Providence	Rhode Island	United States
22	Germantown	Tennessee	United States
23	Arlington	Texas	United States
24	Houston	Texas	United States
25	San Antonio	Texas	United States
26	Norfolk	Virginia	United States
27	Madison	Wisconsin	United States
28	Milwaukee	Wisconsin	United States
29	Vancouver	British Columbia	Canada
30	London	Ontario	Canada
31	Montreal	Quebec	Canada
32	Hamburg		Germany
33	Heidelberg		Germany
34	Hessen		Germany
35	Koeln		Germany
36	Saschen		Germany
37	Stuttgart		Germany
38	Bialystok		Poland
39	Myslowice		Poland
40	Wroclaw		Poland
41	London		United Kingdom
42	Plymouth		United Kingdom
43	Scotland		United Kingdom