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

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Hepatitis C Virus Infection
• Intervention / Treatment: Drug: telaprevir; Drug: VX-222; Drug: VX-222; Drug: ribavirin; Biological: peginterferon-alfa-2a

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 2

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
  • Christchurch, New Zealand
• United States
  • California
    • La Jolla, California, United States
    • San Francisco, California, United States
  • Colorado
    • Aurora, Colorado, United States
  • Florida
    • Gainesville, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
    • Marietta, Georgia, United States
  • Maryland
    • Lutherville, Maryland, United States
  • Minnesota
    • Rochester, Minnesota, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • New Jersey
    • Egg Harbor Township, New Jersey, United States
  • New York
    • New York, New York, United States
  • North Carolina
    • Chapel Hill, North Carolina, United States
    • Durham, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Rhode Island
    • Providence, Rhode Island, United States
  • Tennessee
    • Germantown, Tennessee, United States
  • Texas
    • Arlington, Texas, United States
    • San Antonio, Texas, United States
  • Virginia
    • Falls Church, Virginia, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / 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; Drug: VX-222; capsule, 400-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, 100-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: VX-222; capsule, 400-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: VX-222; capsule, 100-mg, twice daily; Drug: VX-222; capsule, 400-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 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: VX-222; capsule, 100-mg, twice daily; Drug: VX-222; capsule, 400-mg, twice daily; Drug: ribavirin; tablet, 1000-mg for subjects weighing <75-kg or 1200-mg for subjects weighing ≥75-kg, 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: VX-222; capsule, 100-mg, twice daily; Drug: VX-222; capsule, 400-mg, twice daily; Drug: ribavirin; tablet, 1000-mg for subjects weighing <75-kg or 1200-mg for subjects weighing ≥75-kg, twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	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)	40 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	36 weeks
Proportion of Subjects Who Have a Viral Breakthrough or Relapse		60 weeks
Plasma Exposures of VX-222 and Telaprevir		12 weeks

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Publications and helpful links

General Publications

• Jiang M, Zhang EZ, Ardzinski A, Tigges A, Davis A, Sullivan JC, Nelson M, Spanks J, Dorrian J, Nicolas O, Bartels DJ, Rao BG, Rijnbrand R, Kieffer TL. Genotypic and phenotypic analyses of hepatitis C virus variants observed in clinical studies of VX-222, a nonnucleoside NS5B polymerase inhibitor. Antimicrob Agents Chemother. 2014 Sep;58(9):5456-65. doi: 10.1128/AAC.03052-14. Epub 2014 Jun 30.
• Di Bisceglie AM, Sulkowski M, Gane E, Jacobson IM, Nelson D, DeSouza C, Alves K, George S, Kieffer T, Zhang EZ, Kauffman R, Asmal M, Koziel MJ. VX-222, a non-nucleoside NS5B polymerase inhibitor, in telaprevir-based regimens for genotype 1 hepatitis C virus infection. Eur J Gastroenterol Hepatol. 2014 Jul;26(7):761-73. doi: 10.1097/MEG.0000000000000084.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: March 1, 2010
• First Submitted That Met QC Criteria: March 2, 2010
• First Posted (Estimate): March 4, 2010

Study Record Updates

• Last Update Posted (Actual): September 30, 2020
• Last Update Submitted That Met QC Criteria: September 22, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: VX-950
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Infections; Hepatitis; Hepatitis A; Hepatitis C; Virus Diseases; Hepatitis, Chronic; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Peginterferon alfa-2a
• Other Study ID Numbers: VX09-222-103