REPEAT Study - A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) Therapy in Combination With COPEGUS (Ribavirin) in Patients With Chronic Hepatitis C (CHC) Who Did Not Respond to Previous PegIntron (Peginterferon Alfa-2b (12KD))/Ribavirin Combination Therapy

A Randomized, Open-label Study of the Effect of PEGASYS Combined With Ribavirin on Sustained Virologic Response in Patients With Chronic Hepatitis C Who Did Not Respond to Previous Pegintron/Ribavirin Combination Therapy

This 4 arm study is designed for patients with CHC who have not responded to peginterferon alfa-2b (12KD)/ribavirin combination therapy. In these patients, the effects of lengthening the duration of treatment, as well as including an initial 12-week period of high-dose PEGASYS (360 micrograms sc), are compared with the standard combination therapy of PEGASYS (180 micrograms sc) and ribavirin (1000-1200mg po). The anticipated time on study treatment is 1-2 years and the target sample size is 500+ individuals.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: peginterferon alfa-2a [Pegasys]; Drug: Ribavirin; Drug: Ribavirin; Drug: peginterferon alfa-2a [Pegasys]; Drug: peginterferon alfa-2a [Pegasys]; Drug: peginterferon alfa-2a [Pegasys]

• Study Type: Interventional
• Enrollment (Actual): 948
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
  • Gent, Belgium, 9000
  • Leuven, Belgium, 3000
• Brazil
  • Rio de Janeiro, Brazil, 20270-901
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1H2
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
    • Toronto, Ontario, Canada, M6H 3M1
• France
  • Clichy, France, 92118
  • Creteil, France, 94010
  • Lille, France, 59037
  • Lyon, France, 69288
  • Marseille, France, 13385
  • Montpellier, France, 34295
  • Paris, France, 75651
  • Pessac, France, 33604
  • Toulouse, France, 31059
• Germany
  • Berlin, Germany, 13353
  • Bochum, Germany, 44791
  • Bonn, Germany, 53127
  • Düsseldorf, Germany, 40225
  • Düsseldorf, Germany, 40237
  • Erlangen, Germany, 91054
  • Frankfurt Am Main, Germany, 60596
  • Freiburg, Germany, 79106
  • Hamburg, Germany, 20246
  • Hannover, Germany, 30625
  • Heidelberg, Germany, 69120
  • Homburg/saar, Germany, 66424
  • Kassel, Germany, 34125
  • Kiel, Germany, 24105
  • Köln, Germany, 50937
  • Mainz, Germany, 55101
  • Muenchen, Germany, 81377
  • Oberhausen, Germany, 46145
  • Wuerzburg, Germany, 97080
• Greece
  • Alexandroupolis, Greece, 68100
  • Athens, Greece, 11527
  • Athens, Greece, 10552
  • Thessaloniki, Greece, 546 42
• Italy
  • Bari, Italy, 70100
  • Bologna, Italy, 40138
  • Milano, Italy, 20122
  • Padova, Italy, 35128
  • Palermo, Italy, 90127
  • Roma, Italy, 00133
  • Torino, Italy, 10126
• Portugal
  • Coimbra, Portugal, 3000-075
  • Lisboa, Portugal, 1649-035
  • Lisboa, Portugal, 1150-314
• Spain
  • Alicante, Spain, 03010
  • Barcelona, Spain, 08036
  • Granada, Spain, 18003
  • Madrid, Spain, 28046
  • Madrid, Spain, 28007
  • Madrid, Spain, 28035
  • Málaga, Spain, 29010
  • Santander, Spain, 39008
  • Sevilla, Spain, 41014
  • Valencia, Spain, 46014
• Sweden
  • Goeteborg, Sweden, 41685
  • Huddinge, Sweden, 14186
  • Lund, Sweden, 22185
• Switzerland
  • Zürich, Switzerland, 8091
• Turkey
  • Ankara, Turkey, 06100
  • Istanbul, Turkey, 81190
  • Istanbul, Turkey, 34390
  • Izmir, Turkey, 35100
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
• United States
  • Alabama
    • Mobile, Alabama, United States, 36693
  • Arizona
    • Scottsdale, Arizona, United States, 85259
  • California
    • Los Angeles, California, United States, 90033
    • Pasadena, California, United States, 91105
    • San Diego, California, United States, 92123
    • Ukiah, California, United States, 95482
  • Connecticut
    • Farmington, Connecticut, United States, 06030
  • Florida
    • Bradenton, Florida, United States, 34243
    • Hollywood, Florida, United States, 33021
    • Jacksonville, Florida, United States, 32256
  • Georgia
    • Atlanta, Georgia, United States, 30308
    • Atlanta, Georgia, United States, 30309
    • Savannah, Georgia, United States, 31404
  • Illinois
    • Chicago, Illinois, United States, 60611
    • Chicago, Illinois, United States, 60612
  • Iowa
    • Des Moines, Iowa, United States, 50312
  • Maryland
    • Baltimore, Maryland, United States, 21224
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
    • Boston, Massachusetts, United States, 02114
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404-4565
    • Rochester, Minnesota, United States, 55905
  • Missouri
    • Kansas City, Missouri, United States, 64131
    • St Louis, Missouri, United States, 63110
  • New Jersey
    • Florham Park, New Jersey, United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
  • New York
    • Williamsville, New York, United States, 14221
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17604-3200
    • Philadelphia, Pennsylvania, United States, 19104
  • Rhode Island
    • Cranston, Rhode Island, United States, 02920
  • Tennessee
    • Memphis, Tennessee, United States, 38120
    • Nashville, Tennessee, United States, 37211
  • Texas
    • Austin, Texas, United States, 78758
    • Houston, Texas, United States, 77054
  • Utah
    • Salt Lake City, Utah, United States, 84121
  • Vermont
    • Burlington, Vermont, United States, 05401
  • Virginia
    • Richmond, Virginia, United States, 23249

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• adult patients >=18 years of age;
• CHC infection;
• liver biopsy (in <24 calendar months of first dose), with results consistent with CHC infection;
• use of 2 forms of contraception during study and 6 months after the study in both men and women;
• Lack of response to previous treatment with peginterferon alfa-2b (12KD)/ribavirin combination therapy given for >=12 weeks.

Exclusion Criteria:

• women who are pregnant or breastfeeding;
• male partners of women who are pregnant;
• conditions associated with decompensated liver disease;
• other forms of liver disease, including liver cancer;
• human immunodeficiency virus infection.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: peginterferon alfa-2a [Pegasys]; 180 micrograms sc weekly for 48 weeks; Drug: Ribavirin; 1000/1200mg po daily for 72 weeks; Drug: Ribavirin; 1000/1200mg po daily for 48 weeks; Drug: peginterferon alfa-2a [Pegasys]; 360 micrograms sc weekly for 12 weeks, followed by 180 micrograms sc weekly for 60 weeks; Drug: peginterferon alfa-2a [Pegasys]; 360 micrograms sc weekly for 12 weeks, followed by 180 micrograms sc weekly for 36 weeks.; Drug: peginterferon alfa-2a [Pegasys]; 180 micrograms sc weekly for 72 weeks
Experimental: 2	Drug: peginterferon alfa-2a [Pegasys]; 180 micrograms sc weekly for 48 weeks; Drug: Ribavirin; 1000/1200mg po daily for 72 weeks; Drug: Ribavirin; 1000/1200mg po daily for 48 weeks; Drug: peginterferon alfa-2a [Pegasys]; 360 micrograms sc weekly for 12 weeks, followed by 180 micrograms sc weekly for 60 weeks; Drug: peginterferon alfa-2a [Pegasys]; 360 micrograms sc weekly for 12 weeks, followed by 180 micrograms sc weekly for 36 weeks.; Drug: peginterferon alfa-2a [Pegasys]; 180 micrograms sc weekly for 72 weeks
Experimental: 3	Drug: peginterferon alfa-2a [Pegasys]; 180 micrograms sc weekly for 48 weeks; Drug: Ribavirin; 1000/1200mg po daily for 72 weeks; Drug: Ribavirin; 1000/1200mg po daily for 48 weeks; Drug: peginterferon alfa-2a [Pegasys]; 360 micrograms sc weekly for 12 weeks, followed by 180 micrograms sc weekly for 60 weeks; Drug: peginterferon alfa-2a [Pegasys]; 360 micrograms sc weekly for 12 weeks, followed by 180 micrograms sc weekly for 36 weeks.; Drug: peginterferon alfa-2a [Pegasys]; 180 micrograms sc weekly for 72 weeks
Active Comparator: 4	Drug: peginterferon alfa-2a [Pegasys]; 180 micrograms sc weekly for 48 weeks; Drug: Ribavirin; 1000/1200mg po daily for 72 weeks; Drug: Ribavirin; 1000/1200mg po daily for 48 weeks; Drug: peginterferon alfa-2a [Pegasys]; 360 micrograms sc weekly for 12 weeks, followed by 180 micrograms sc weekly for 60 weeks; Drug: peginterferon alfa-2a [Pegasys]; 360 micrograms sc weekly for 12 weeks, followed by 180 micrograms sc weekly for 36 weeks.; Drug: peginterferon alfa-2a [Pegasys]; 180 micrograms sc weekly for 72 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Sustained Virological Response Rate	Sustained Virological Response (SVR) was defined as the percentage of participants with a undetectable hepatitis C virus- ribonucleic acid (HCV RNA) 24 weeks after the end of the treatment period (defined as a single last HCV RNA < 50 International Units Per Millilitre (IU/mL) measured >= 20 weeks after treatment end, ie, >=140 days after treatment end.	Up to 72 weeks (Group A) and 48 weeks (Group D)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Sustained Virological Response (Groups A + B vs Groups C + D)	SVR was defined as the percentage of participants with a undetectable hepatitis C virus- ribonucleic acid (HCV RNA) 24 weeks after the end of the treatment period (defined as a single last HCV RNA < 50 International Units Per Millilitre (IU/mL) measured >= 20 weeks after treatment end, ie, >=140 days after treatment end.	At Week 48 and Week 72
Number of Participants With Sustained Virological Response (Groups A + C vs Groups B + D)	SVR was defined as the percentage of participants with a undetectable hepatitis C virus- ribonucleic acid (HCV RNA) 24 weeks after the end of the treatment period (defined as a single last HCV RNA < 50 International Units Per Millilitre (IU/mL) measured >= 20 weeks after treatment end, ie, >=140 days after treatment end.	At Week 48 and Week 72
Percentage of Participants With Undetectable HCV-RNA	The percentage of participants with a undetectable HCV RNA 24 weeks after the end of the treatment period (defined as a single last HCV RNA < 50 IU/mL measured >= 20 weeks after treatment end, ie, >=140 days after treatment end) are reported. End-of-treatment (EOT) virological response is defined as last HCV RNA measurement that is not detectable (<50 IU/mL) at study day of last dose of study medication (+/- 28 days).	At Week 12, 24, 48 and EOT
Percentage of Participants With >=2log Drop in HCV-RNA	Reduction in HCV-RNA titers of at least 2 log10 after 12/24 weeks of study treatment (i.e. 99% reduction of viral load) was analyzed. Percentage of participants with at least a 2 log10 drop of HCV-RNA at study week 12 and 24 (lower limit of quantitation 600 IU/mL) as compared to baseline or non-detectable HCV-RNA (lower limit of detection 50 IU/mL) were reported.	At Week 12 and 24
Change From Baseline in Reduction of HCV Viremia (Groups A + B vs Groups C + D)	The mean change from baseline in HCV RNA level (reduction in viral load) at Week 12 and 24 were determined. HCV RNA result were not detectable (<50 IU/ML) and not quantifiable (<600 IU/ML). Baseline value were assessed on Day 1 before the administration of the first dose of study drug.	At Week 12 and 24
Percentage of Participants With Maintenance of Actual End-of-Treatment Virological Response	Maintenance of end-of-treatment virological response was assessed based on all participants treated and according to the actual treatment period (backward imputation method). The percentage of participants who maintained their end-of-treatment virological response was determined. Maintenance of actual end-of-treatment virological response was calculated by dividing the number of participants with a virological response both at the end of the actual untreated follow-up period and at the end of the actual treatment period by the number of participants with a virological response at the actual end of treatment.	Week 96 (Group A and C) and Week 72 (Group B and D)
Percentage of Participants With Relapse After End of Treatment	The percentage of participants who relapsed (loss of response) after having achieved a virological response at the end of treatment was determined.	Week 96 (Group A and C) and Week 72 (Group B and D)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Marcellin P, Craxi A, Brandao-Mello CE, Di Bisceglie AM, Andreone P, Freilich B, Rajender Reddy K, Olveira Martin A, Teuber G, Messinger D, Hooper G, Wat C, Tatsch F, Jensen DM. Predicting early and sustained virological responses in prior nonresponders to pegylated interferon alpha-2b plus ribavirin retreated with peginterferon alpha-2a plus ribavirin and the benefit-risk ratio of retreatment. J Clin Gastroenterol. 2013 Oct;47(9):786-93. doi: 10.1097/MCG.0b013e31827b9b45.

Helpful Links

• This is a full publication titled Re-treatment of Patients With Chronic Hepatitis C Who Do Not Respond to Peginterferon- alfa2b, A Randomized Trial

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: July 12, 2004
• First Submitted That Met QC Criteria: July 13, 2004
• First Posted (Estimate): July 14, 2004

Study Record Updates

• Last Update Posted (Estimate): January 14, 2016
• Last Update Submitted That Met QC Criteria: December 10, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Immunologic Factors; Interferon-alpha; Ribavirin; Peginterferon alfa-2a
• Other Study ID Numbers: MV17150