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 - Full Text View

Sponsor:	Vertex Pharmaceuticals Incorporated
Information provided by (Responsible Party):	Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:	NCT01080222

Purpose

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.

Condition	Intervention	Phase
Chronic Hepatitis C Virus Infection	Drug: telaprevir Drug: VX-222 Drug: ribavirin Biological: peginterferon-alfa-2a	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin Peginterferon Alfa-2a Telaprevir

U.S. FDA Resources

Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:

Safety and Tolerability [ Time Frame: 40 weeks ] [ Designated as safety issue: Yes ]
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)

Secondary Outcome Measures:

Proportion of Subjects Who Achieve a Sustained Viral Response [ Time Frame: 24 weeks after the completion of the last dose of the assigned study drug treatment regimen ] [ Designated as safety issue: No ]
Undetectable HCV RNA Measurements [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]
- 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
Proportion of Subjects Who Have a Viral Breakthrough or Relapse [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]
Plasma Exposures of VX-222 and Telaprevir [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	150
Study Start Date:	August 2010
Estimated Primary Completion Date:	August 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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
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, 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: 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: 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 Drug: VX-222 capsule, 400-mg, twice daily
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: ribavirin tablet, 1000-mg for subjects weighing <75-kg or 1200-mg for subjects weighing ≥75-kg, twice daily Drug: VX-222 capsule, 400-mg, 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: ribavirin tablet, 1000-mg for subjects weighing <75-kg or 1200-mg for subjects weighing ≥75-kg, twice daily Drug: VX-222 capsule, 400-mg, twice daily

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01080222

Show 21 Study Locations

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

Investigators

Study Director:

Medical Monitor

Vertex Pharmaceuticals Incorporated

More Information

No publications provided

Responsible Party:	Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:	NCT01080222 History of Changes
Other Study ID Numbers:	VX09-222-103
Study First Received:	March 1, 2010
Last Updated:	May 18, 2012
Health Authority:	New Zealand: Medsafe United States: Food and Drug Administration

Keywords provided by Vertex Pharmaceuticals Incorporated:

VX-950

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Virus Diseases
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections

Flaviviridae Infections
Ribavirin
Peginterferon alfa-2a
Interferon-alpha
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 23, 2012