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

Vertex Pharmaceuticals

Status and phase: Terminated; Phase 2

Conditions: Chronic Hepatitis C Virus Infection

Treatments: Biological: peginterferon-alfa-2a; Drug: ribavirin; Drug: VX-222; Drug: telaprevir

Study type: Interventional

Funder types: Industry

Identifiers

NCT01080222

VX09-222-103

Details and patient eligibility

About

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.

Enrollment: 152 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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152 participants in 6 patient groups

Treatment Arm A

Experimental group

Description:

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.

Treatment:

Drug: VX-222

Drug: VX-222

Drug: telaprevir

Treatment Arm B

Experimental group

Description:

Treatment Arm B was discontinued as a result of patients meeting a pre-defined stopping rule relating to viral breakthrough.

Treatment:

Drug: VX-222

Drug: VX-222

Drug: telaprevir

Treatment Arm C

Experimental group

Description:

* 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.

Treatment:

Biological: peginterferon-alfa-2a

Drug: VX-222

Drug: ribavirin

Drug: VX-222

Drug: telaprevir

Treatment Arm D

Experimental group

Description:

* 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.

Treatment:

Biological: peginterferon-alfa-2a

Drug: VX-222

Drug: ribavirin

Drug: VX-222

Drug: telaprevir

Treatment Arm E

Experimental group

Description:

* 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.

Treatment:

Drug: VX-222

Drug: ribavirin

Drug: VX-222

Drug: telaprevir

Treatment Arm F

Experimental group

Description:

* 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.

Treatment:

Drug: VX-222

Drug: ribavirin

Drug: VX-222

Drug: telaprevir