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A Study of Telaprevir (VX-950), Pegasys and Copegus in Hepatitis C (PROVE3)

Phase 2
Completed
Conditions
Hepatitis C
Interventions
Drug: Matching Placebo
Drug: Pegylated Interferon Alfa 2a
Registration Number
NCT00420784
Lead Sponsor
Vertex Pharmaceuticals Incorporated
Brief Summary

The PROVE3 trial is a partially double blinded, randomized, Phase 2 research study of an investigational drug, Telaprevir (VX-950) or Placebo, with Pegylated Interferon Alfa 2a (Peg-IFN-alfa-2a, Pegasys®), and Ribavirin (RBV, Copegus®) in people with genotype 1 hepatitis C who have not achieved a Sustained Viral Response (SVR) with a previous treatment of interferon therapy.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
465
Inclusion Criteria
  • Males and females between 18 and 70 years old
  • Detectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) greater than or equal to (>=) 10,000 international units per milliliter (IU/mL)
  • Must have chronic hepatitis C (genotype 1) and have already received at least one prior course of pegylated interferon alfa 2a with ribavirin
  • Cannot also be infected with Human Immunodeficiency Virus or hepatitis B
  • Must be judged to be in general good health and able to receive Pegasys® and Copegus®
  • No drug or alcohol abuse in the last year
  • Must agree to use two effective methods of birth control during the study and for 6 months after you stop taking study medication. One of the methods needs to be a 'barrier' method (condom or diaphragm)
  • If you are a woman, you cannot be in this study if you are pregnant or nursing
Exclusion Criteria
  • Participation in any clinical trial of a HCV protease inhibitor of any duration
  • Prior response to therapy and failure to achieve SVR which was due to treatment non-compliance
  • Any other cause of significant liver disease in addition to hepatitis C; this may include but is not limited to, hepatitis B, drug or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, nonalcoholic steatohepatitis, or primary biliary cirrhosis
  • Diagnosed or suspected hepatocellular carcinoma
  • History of or current evidence of decompensated liver disease
  • Participation in any clinical trial of an investigational drug within 90 days before drug administration or participation in more than 2 drug studies in the last 12 months (exclusive of the current study)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Telaprevir 24 Week+Peg-IFN-alfa-2a,RBV 48 WeekTelaprevirSingle loading dose of telaprevir 1125 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily for 24 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks.
Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 WeekRibavirinSingle loading dose of telaprevir 1125 milligram (mg) tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) tablet orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (\<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (\>=) 75 kg, for 24 weeks.
PBO 24 Week+Peg-IFN-alfa-2a, RBV 48 WeekMatching PlaceboPlacebo (PBO) matched to telaprevir tablet orally thrice daily for 24 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks.
Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 WeekTelaprevirSingle loading dose of telaprevir 1125 milligram (mg) tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) tablet orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (\<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (\>=) 75 kg, for 24 weeks.
Telaprevir 24 Week+Peg-IFN-alfa-2a,RBV 48 WeekRibavirinSingle loading dose of telaprevir 1125 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily for 24 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks.
Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 WeekPegylated Interferon Alfa 2aSingle loading dose of telaprevir 1125 milligram (mg) tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) tablet orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (\<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (\>=) 75 kg, for 24 weeks.
Telaprevir 24 Week+Peg-IFN-alfa-2a,RBV 48 WeekPegylated Interferon Alfa 2aSingle loading dose of telaprevir 1125 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily for 24 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks.
Telaprevir 24 Week+Peg-IFN-alfa-2a 24 WeekPegylated Interferon Alfa 2aSingle loading dose of telaprevir 1125 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection, for 24 weeks.
PBO 24 Week+Peg-IFN-alfa-2a, RBV 48 WeekPegylated Interferon Alfa 2aPlacebo (PBO) matched to telaprevir tablet orally thrice daily for 24 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks.
Telaprevir 24 Week+Peg-IFN-alfa-2a 24 WeekTelaprevirSingle loading dose of telaprevir 1125 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection, for 24 weeks.
PBO 24 Week+Peg-IFN-alfa-2a, RBV 48 WeekRibavirinPlacebo (PBO) matched to telaprevir tablet orally thrice daily for 24 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks.
Primary Outcome Measures
NameTimeMethod
Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing24 weeks after the completion of study drug dosing (up to Week 72)

The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL).

Secondary Outcome Measures
NameTimeMethod
Percentage of Subjects With Undetectable Plasma HCV RNA at Completion of Study Drug DosingCompletion of study drug dosing (up to Week 48)

The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL).

Percentage of Subjects With Undetectable Plasma HCV RNAUp to Week 96 (24 weeks after last dose of study drug for PBO group; 48 weeks after last dose of study drug for telaprevir groups)

Percentage of subjects with undetectable HCV RNA at 24 weeks after last dose of study drug for treatment group "PBO 24 Week+Peg-IFN-alfa-2a, RBV 48 Week" and at 48 weeks after last dose of study drug for treatment groups "Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week", "Telaprevir 24 Week+Peg-IFN-alfa-2a,RBV 48 Week" and "Telaprevir 24 Week+Peg-IFN-alfa-2a 24 Week" were presented. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL).

Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)Baseline up to 2 weeks after last dose of study drug (up to Week 50)

AE: any adverse change from the subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. "Study drug" includes all investigational agents (including placebo, if applicable) administered during the course of the study.

Number of Subjects With Viral RelapseAfter last dose of study drug up to 24 week antiviral follow-up (up to Week 72)

Viral relapse was defined as having detectable HCV RNA during antiviral follow-up. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL).

Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of TelaprevirWeek 2, 4, 8, 12, 16, 24

Only subjects who received telaprevir were to be analyzed for this outcome. Maximum, minimum and average plasma concentrations observed during assessment period were reported.

Trial Locations

Locations (34)

North Shore University Hospital

🇺🇸

Manhasset, New York, United States

Academic Medical Center

🇳🇱

Amsterdam, Netherlands

University of Florida

🇺🇸

Gainesville, Florida, United States

Mayo Clinic Jacksonville

🇺🇸

Jacksonville, Florida, United States

University Hepatitis Center at Bach & Godofsky

🇺🇸

Sarasota, Florida, United States

Borland-Groover Clinic

🇺🇸

Jacksonville, Florida, United States

University Clinic Frankfurt, Department of Internal Medicine

🇩🇪

Frankfurt, Germany

Leiden University Medical Center

🇳🇱

Leiden, Netherlands

Cedars-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

Virology Treatment Center, Maine Medical Center

🇺🇸

Portland, Maine, United States

Gulf Coast Research, LLC

🇺🇸

Baton Rouge, Louisiana, United States

Johns Hopkins University

🇺🇸

Baltimore, Maryland, United States

Columbia Gastroenterology Associates, PA

🇺🇸

Columbia, South Carolina, United States

Memphis Gastroenterology Group

🇺🇸

Germantown, Tennessee, United States

University of California, San Diego

🇺🇸

San Diego, California, United States

University of California San Francisco

🇺🇸

San Francisco, California, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

University Internal Medicine Associates, Inc.

🇺🇸

Cincinnati, Ohio, United States

Advanced Liver Therapies

🇺🇸

Houston, Texas, United States

Alamo Medical Research

🇺🇸

San Antonio, Texas, United States

Birmingham Gastroenterology Associates

🇺🇸

Birmingham, Alabama, United States

University of Colorado Health Sciences Center

🇺🇸

Denver, Colorado, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Kaiser Permanente Hepatology Research

🇺🇸

San Diego, California, United States

USC

🇺🇸

Los Angeles, California, United States

Saint Louis University

🇺🇸

St Louis, Missouri, United States

BC Hepatitis Program

🇨🇦

Vancouver, British Columbia, Canada

Toronto Western Hospital

🇨🇦

Toronto, Ontario, Canada

Liver Institute at Methodist Dallas

🇺🇸

Dallas, Texas, United States

Erasmus MC University Medical Center

🇳🇱

Rotterdam, Netherlands

University of Calgary Medical Clinic - Health Science Centre

🇨🇦

Calgary, Alberta, Canada

Universitatsmedizin Berlin

🇩🇪

Berlin, Germany

Metropolitan Research

🇺🇸

Fairfax, Virginia, United States

Beth Isreal Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

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