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

NCT01080222 | Terminated Phase 2

• 1 other identifier: VX09-222-103
• Study Type: interventional
• Target: 152
• Locations: 2 countries
• Sites: 21

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.

Conditions

Chronic Hepatitis C Virus Infection

Keywords

VX-950

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

• Proportion of Subjects Who Have a Viral Breakthrough or Relapse

  60 weeks

• Plasma Exposures of VX-222 and Telaprevir

  12 weeks

Study Arms (6)

Treatment Arm A

EXPERIMENTAL

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; Drug: VX-222

Treatment Arm B

EXPERIMENTAL

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

Drug: telaprevir; Drug: VX-222

Treatment Arm C

EXPERIMENTAL

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

Treatment Arm D

EXPERIMENTAL

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

Treatment Arm E

EXPERIMENTAL

* 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; Drug: ribavirin; Drug: VX-222

Treatment Arm F

EXPERIMENTAL

* 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; Drug: ribavirin; Drug: VX-222

Interventions

telaprevir DRUG

tablet, 1125-mg, twice daily

Treatment Arm A; Treatment Arm B; Treatment Arm C; Treatment Arm D; Treatment Arm E; Treatment Arm F

VX-222 DRUG

capsule, 100-mg, twice daily

Treatment Arm A; Treatment Arm C

ribavirin DRUG

tablet, 1000-mg for subjects weighing \<75-kg or 1200-mg for subjects weighing ≥75-kg, twice daily

Treatment Arm C; Treatment Arm D; Treatment Arm E; Treatment Arm F

peginterferon-alfa-2a BIOLOGICAL

subcutaneous injection, 180-mcg, once weekly

Treatment Arm C; Treatment Arm D

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (21)

Unknown Facility

La Jolla, California, United States

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San Francisco, California, United States

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Aurora, Colorado, United States

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Gainesville, Florida, United States

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Atlanta, Georgia, United States

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Marietta, Georgia, United States

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Lutherville, Maryland, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Egg Harbor, New Jersey, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Durham, North Carolina, United States

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Cincinnati, Ohio, United States

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Providence, Rhode Island, United States

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Germantown, Tennessee, United States

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Arlington, Texas, United States

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San Antonio, Texas, United States

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Unknown Facility

Falls Church, Virginia, United States

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Unknown Facility

Auckland, New Zealand

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Unknown Facility

Christchurch, New Zealand

Location

Related Publications (2)

• 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.

  PMID: 24982088 DERIVED

• 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.

  PMID: 24901821 DERIVED

MeSH Terms

Interventions

telaprevir; lomibuvir; Ribavirin; peginterferon alfa-2a

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Medical Monitor

  Vertex Pharmaceuticals Incorporated

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2010
• First Posted: March 4, 2010
• Study Start: August 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: November 1, 2013
• Last Updated: September 30, 2020

Record last verified: 2020-09

Locations

NZ (2); US (19)