A study to evaluate the safety and effectiveness of a quadruple drugregimen (VX-222, telaprevir, peginterferon alfa-2a and ribavirin) intreating chronic hepatitis C virus in subjects with cirrhosis who aretreatment naive or nonresponders and relapsers to previous Peg-IFN/Ribavirin therapy.

Conditions: Chronic Hepatitis C Virus
MedDRA version: 16.0Level: PTClassification code 10008912Term: Chronic hepatitis CSystem Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2011-004150-26-PL

Lead Sponsor: Vertex Pharmaceuticals

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 114

Inclusion Criteria

must be between the ages of 18 and 70 years
- Subjects must have genotype 1 CHC and laboratory evidence of HCV
infection for at least 6 months before the Screening Visit
- Subjects must have documentation of compensated cirrhosis
- Subjects must fit one of the following categories:
• Treatment-naïve: never received treatment for hepatitis C
• Prior null responder: had <2-log10 decrease from baseline in HCV RNA
concentration at the Week 12 assessment after prior Peg-IFN/RBV
treatment of at least 12 weeks.
• Prior partial responder: had a =2-log10 decrease in HCV RNA
concentration at the Week 12 assessment after prior Peg-IFN/RBV
treatment of at least 12 weeks but never had undetectable HCV RNA
levels while on treatment.
• Prior relapser: had undetectable HCV RNA at EOT after prior Peg-
IFN/RBV treatment of at least 12 weeks but detectable HCV RNA after
the end of prior treatment.
For null and partial responders, the Week 12 assessment of HCV RNA
response used should be from a sample collected between no earlier
than Week 11 and no later than Week 16. If more than one assessment
from this time period is available, the assessment closest to Week 12
should be used.
The following information related to the virologic response to the last
course of Peg IFN/RBV therapy, if applicable, must be available in the
medical records of the subject:
• HCV RNA results before the start of treatment and at Week 12
assessment after start of treatment or documentation of the total
treatment duration and log fold-change in HCV RNA.
• Last dose of prior therapy must be at least 12 weeks before first dose
of study drug given under this protocol.
- Subject s must have plasma HCV RNA of =4.0 log10 IU/mL (10000
IU/mL).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 114
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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
-History of any illness that, in the opinion of the investigator or general
practitioner might confound the results of the study or pose an
additional risk to the subject
- Any contraindication to Peg-IFN or RBV therapy, or history of severe
AEs while on Peg-IFN or RBV
- Child-Pugh Score =7, or other clinical evidence of hepatic
decompensation
- Any other cause of significant liver disease in addition to hepatitis C
- Diagnosed or suspected hepatocellular carcinoma
- History of organ transplant, with the exception of corneal transplants
and skin grafts
- A medical condition that requires frequent or prolonged use of systemic
corticosteroids or immunosuppressive drugs
- History of acute pancreatitis
- History or other clinical evidence of chronic pulmonary disease
associated with functional impairment
- History of other evidence of sever retinopathy or clinically significant
ophthalmological disorder
- History of illicit substance or alcohol abuse within 1 year before the
Screening Visit
- Blood donation of approximately 1 pint (500 mL) within 56 days before
dosing

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the antiviral efficacy of a quadruple drug regimen (VX-222,<br>telaprevir, Peg-IFN and RBV) in subjects with genotype 1 CHC with<br>compensated cirrhosis, who are treatment naive or were nonresponders<br>(partial or null) or relapsers to previous Peg-IFN/RBV therapy.;Secondary Objective: To evaluate the safety and tolerability of the quadruple regimen in<br>subjects with compensated cirrhosis<br>To assess the efficacy of quadruple regimen across interleukin-28B (IL-<br>28B) genotypes<br>To characterize HCV variants in subjects on the quadruple regimen who<br>have treatment failure<br>To characterize the pharmacokinetics (PK) of VX-222 and telaprevir in<br>the quadruple regimen in subjects with compensated cirrhosis;Primary end point(s): The proportion of subjects who have an SVR (i.e., sustain an HCV RNA concentration below the lower limit of quantitation at 12 weeks after last planned dose of treatment (SVR12);Timepoint(s) of evaluation of this end point: 12 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -The safety and tolerability as assessed by AEs, vital signs, 12-lead<br>electrocardiograms (ECG), and laboratory assessments (serum<br>chemistry, hematology, and urinalysis)<br>- Proportion of subjects who have an SVR24 weeks after the last planned<br>dose of the study drug (SVR24)<br>- Proportion of subjects who achieve undetectable HCV RNA at Weeks<br>2,4,8, and 12 and <LLOQ at the end of treatment<br>-Proportion of subjects who have on-treatment virologic failure, defined<br>as subjects who either meet a futility rule or complete assigned<br>treatment duration and have detectable HCV RNA at the end of study<br>drug treatment<br>- Proportion of subjects who relapse at end of treatment<br>- The association of IL-28B genotype with SVR12<br>- The amino acid sequence of the NS3 and NS5B proteins in subjects who<br>have treatment failure<br>- VX-222, telaprevir, RBV plasma concentrations; and Peg-IFN serum<br>concentrations;Timepoint(s) of evaluation of this end point: up to 52 weeks

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