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

Primary Purpose

Hepatitis C

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Telaprevir
Ribavirin
Pegylated Interferon Alfa 2a
Matching Placebo
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C focused on measuring Genotype 1

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Birmingham Gastroenterology Associates
  • Cedars-Sinai Medical Center
  • USC
  • Kaiser Permanente Hepatology Research
  • University of California, San Diego
  • University of California San Francisco
  • University of Colorado Health Sciences Center
  • University of Florida
  • Borland-Groover Clinic
  • Mayo Clinic Jacksonville
  • University Hepatitis Center at Bach & Godofsky
  • Gulf Coast Research, LLC
  • Virology Treatment Center, Maine Medical Center
  • Johns Hopkins University
  • Beth Isreal Deaconess Medical Center
  • Henry Ford Hospital
  • Saint Louis University
  • North Shore University Hospital
  • University Internal Medicine Associates, Inc.
  • Cleveland Clinic
  • Columbia Gastroenterology Associates, PA
  • Memphis Gastroenterology Group
  • Liver Institute at Methodist Dallas
  • Advanced Liver Therapies
  • Alamo Medical Research
  • Metropolitan Research
  • University of Calgary Medical Clinic - Health Science Centre
  • BC Hepatitis Program
  • Toronto Western Hospital
  • Universitatsmedizin Berlin
  • University Clinic Frankfurt, Department of Internal Medicine
  • Academic Medical Center
  • Leiden University Medical Center
  • Erasmus MC University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week

Telaprevir 24 Week+Peg-IFN-alfa-2a,RBV 48 Week

Telaprevir 24 Week+Peg-IFN-alfa-2a 24 Week

PBO 24 Week+Peg-IFN-alfa-2a, RBV 48 Week

Arm Description

Single 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.

Single 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.

Single 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.

Placebo (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.

Outcomes

Primary Outcome Measures

Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing
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

Percentage of Subjects With Undetectable Plasma HCV RNA at Completion of Study Drug Dosing
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 RNA
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)
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 Relapse
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 Telaprevir
Only subjects who received telaprevir were to be analyzed for this outcome. Maximum, minimum and average plasma concentrations observed during assessment period were reported.

Full Information

First Posted
January 8, 2007
Last Updated
July 9, 2014
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT00420784
Brief Title
A Study of Telaprevir (VX-950), Pegasys and Copegus in Hepatitis C (PROVE3)
Official Title
A Phase 2 Study of Telaprevir (VX-950) in Combination With Peginterferon Alfa-2a (Pegasys®), and Ribavirin (Copegus®) in Subjects With Genotype 1 Hepatitis C Who Have Not Achieved Sustained Viral Response With a Prior Course of Interferon Based Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C
Keywords
Genotype 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
465 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week
Arm Type
Experimental
Arm Description
Single 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.
Arm Title
Telaprevir 24 Week+Peg-IFN-alfa-2a,RBV 48 Week
Arm Type
Experimental
Arm Description
Single 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.
Arm Title
Telaprevir 24 Week+Peg-IFN-alfa-2a 24 Week
Arm Type
Experimental
Arm Description
Single 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.
Arm Title
PBO 24 Week+Peg-IFN-alfa-2a, RBV 48 Week
Arm Type
Placebo Comparator
Arm Description
Placebo (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.
Intervention Type
Drug
Intervention Name(s)
Telaprevir
Other Intervention Name(s)
VX-950
Intervention Description
tablet
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Other Intervention Name(s)
RBV
Intervention Description
tablet
Intervention Type
Drug
Intervention Name(s)
Pegylated Interferon Alfa 2a
Other Intervention Name(s)
Peg-IFN-alfa-2a
Intervention Description
Solution for injection
Intervention Type
Drug
Intervention Name(s)
Matching Placebo
Intervention Description
Tablet
Primary Outcome Measure Information:
Title
Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing
Description
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).
Time Frame
24 weeks after the completion of study drug dosing (up to Week 72)
Secondary Outcome Measure Information:
Title
Percentage of Subjects With Undetectable Plasma HCV RNA at Completion of Study Drug Dosing
Description
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).
Time Frame
Completion of study drug dosing (up to Week 48)
Title
Percentage of Subjects With Undetectable Plasma HCV RNA
Description
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).
Time Frame
Up 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)
Title
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
Baseline up to 2 weeks after last dose of study drug (up to Week 50)
Title
Number of Subjects With Viral Relapse
Description
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).
Time Frame
After last dose of study drug up to 24 week antiviral follow-up (up to Week 72)
Title
Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir
Description
Only subjects who received telaprevir were to be analyzed for this outcome. Maximum, minimum and average plasma concentrations observed during assessment period were reported.
Time Frame
Week 2, 4, 8, 12, 16, 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Vertex Pharmaceuticals Incorporated
Official's Role
Study Director
Facility Information:
Facility Name
Birmingham Gastroenterology Associates
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
USC
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Kaiser Permanente Hepatology Research
City
San Diego
State/Province
California
Country
United States
Facility Name
University of California, San Diego
City
San Diego
State/Province
California
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
Country
United States
Facility Name
University of Colorado Health Sciences Center
City
Denver
State/Province
Colorado
Country
United States
City
Englewood
State/Province
Colorado
Country
United States
City
Bardenton
State/Province
Florida
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
Country
United States
Facility Name
Borland-Groover Clinic
City
Jacksonville
State/Province
Florida
Country
United States
Facility Name
Mayo Clinic Jacksonville
City
Jacksonville
State/Province
Florida
Country
United States
City
Miami
State/Province
Florida
Country
United States
Facility Name
University Hepatitis Center at Bach & Godofsky
City
Sarasota
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
Facility Name
Gulf Coast Research, LLC
City
Baton Rouge
State/Province
Louisiana
Country
United States
Facility Name
Virology Treatment Center, Maine Medical Center
City
Portland
State/Province
Maine
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
Beth Isreal Deaconess Medical Center
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
Country
United States
Facility Name
Saint Louis University
City
St Louis
State/Province
Missouri
Country
United States
City
Omaha
State/Province
Nebraska
Country
United States
City
Albuquerque
State/Province
New Mexico
Country
United States
Facility Name
North Shore University Hospital
City
Manhasset
State/Province
New York
Country
United States
City
New York
State/Province
New York
Country
United States
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
University Internal Medicine Associates, Inc.
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
Country
United States
City
Hershey
State/Province
Pennsylvania
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
Facility Name
Columbia Gastroenterology Associates, PA
City
Columbia
State/Province
South Carolina
Country
United States
Facility Name
Memphis Gastroenterology Group
City
Germantown
State/Province
Tennessee
Country
United States
Facility Name
Liver Institute at Methodist Dallas
City
Dallas
State/Province
Texas
Country
United States
Facility Name
Advanced Liver Therapies
City
Houston
State/Province
Texas
Country
United States
Facility Name
Alamo Medical Research
City
San Antonio
State/Province
Texas
Country
United States
City
Annandale
State/Province
Virginia
Country
United States
Facility Name
Metropolitan Research
City
Fairfax
State/Province
Virginia
Country
United States
City
Richmond
State/Province
Virginia
Country
United States
City
Seattle
State/Province
Washington
Country
United States
Facility Name
University of Calgary Medical Clinic - Health Science Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N1
Country
Canada
City
Edmonton
State/Province
Alberta
Country
Canada
Facility Name
BC Hepatitis Program
City
Vancouver
State/Province
British Columbia
Country
Canada
City
Winnipeg
State/Province
Manitoba
Country
Canada
Facility Name
Toronto Western Hospital
City
Toronto
State/Province
Ontario
Country
Canada
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Universitatsmedizin Berlin
City
Berlin
Country
Germany
Facility Name
University Clinic Frankfurt, Department of Internal Medicine
City
Frankfurt
Country
Germany
Facility Name
Academic Medical Center
City
Amsterdam
Country
Netherlands
Facility Name
Leiden University Medical Center
City
Leiden
Country
Netherlands
Facility Name
Erasmus MC University Medical Center
City
Rotterdam
Country
Netherlands
City
Santurce
Country
Puerto Rico

12. IPD Sharing Statement

Citations:
PubMed Identifier
21690488
Citation
Li S, Zhu J, Zhang W, Chen Y, Zhang K, Popescu LM, Ma X, Lau WB, Rong R, Yu X, Wang B, Li Y, Xiao C, Zhang M, Wang S, Yu L, Chen AF, Yang X, Cai J. Signature microRNA expression profile of essential hypertension and its novel link to human cytomegalovirus infection. Circulation. 2011 Jul 12;124(2):175-84. doi: 10.1161/CIRCULATIONAHA.110.012237. Epub 2011 Jun 20.
Results Reference
derived
PubMed Identifier
20375406
Citation
McHutchison JG, Manns MP, Muir AJ, Terrault NA, Jacobson IM, Afdhal NH, Heathcote EJ, Zeuzem S, Reesink HW, Garg J, Bsharat M, George S, Kauffman RS, Adda N, Di Bisceglie AM; PROVE3 Study Team. Telaprevir for previously treated chronic HCV infection. N Engl J Med. 2010 Apr 8;362(14):1292-303. doi: 10.1056/NEJMoa0908014. Erratum In: N Engl J Med. 2010 Apr 29;362(17):1647. Dosage error in article text.
Results Reference
derived

Learn more about this trial

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

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