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A Study of Mericitabine in Combination With Telaprevir and Peginterferon Alfa-2a / Ribavirin in Participants With Chronic Hepatitis C

Phase 2
Completed
Conditions
Hepatitis C
Interventions
Registration Number
NCT01482390
Lead Sponsor
Hoffmann-La Roche
Brief Summary

This randomized, double-blind, multi-center, parallel-group study will evaluate the sustained virologic response and the safety of mericitabine (RO5024048) (MCB) in combination with telaprevir (TVR) and peginterferon Alfa-2a (PEG-IFN) / ribavirin (RBV) in participants with chronic Hepatitis C infection.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
80
Inclusion Criteria
  • Chronic hepatitis C infection for at least 6 months duration
  • Hepatitis C genotype 1a or 1b
  • Participants must have discontinued prior hepatitis C treatment at least 12 weeks prior to enrollment in this study
  • Participants showed a previous null response to therapy as defined by < 2 logarithm to the base 10 (log10) international units per milliliter (IU/mL) decrease in viral titer after at least 12 weeks of treatment with PEG-IFN/RBV
Exclusion Criteria
  • Hepatitis C infection with a genotype other than genotype 1a or 1b
  • Body mass index < 18 or >= 36 kilograms per square meters (kg/m^2)
  • Hepatitis A, hepatitis B, or human immunodeficiency virus (HIV) infection
  • Herbal remedies <=1 month prior to the first dose of study drug

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
TVR (12 Weeks), MCB (24 Weeks), PEG-IFN/RBV (48 Weeks)Peginterferon Alfa-2aTwelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with MCB and PEG-IFN/RBV and then 12 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks).
TVR, MCB, Placebo MCB( each for 12Weeks),PEG-IFN/RBV(48 Weeks)PlaceboTwelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with placebo matching to MCB and PEG-IFN/RBV, and then 24 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks).
TVR (12 Weeks), MCB (24 Weeks), PEG-IFN/RBV (24 Weeks)Peginterferon Alfa-2aTwelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with MCB and PEG-IFN/RBV (total treatment duration of 24 weeks).
TVR (12 Weeks), MCB (24 Weeks), PEG-IFN/RBV (48 Weeks)TelaprevirTwelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with MCB and PEG-IFN/RBV and then 12 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks).
TVR(12 Weeks), Placebo MCB (24 Weeks), PEG-IFN/RBV(48 Weeks)PlaceboTwelve weeks of therapy with placebo matching to MCB, TVR, PEG-IFN/RBV, will be followed by 12 weeks of therapy with placebo matching to MCB along with PEG-IFN/RBV , following 24 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks).
TVR (12 Weeks), MCB (24 Weeks), PEG-IFN/RBV (24 Weeks)RibavirinTwelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with MCB and PEG-IFN/RBV (total treatment duration of 24 weeks).
TVR (12 Weeks), MCB (24 Weeks), PEG-IFN/RBV (24 Weeks)MericitabineTwelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with MCB and PEG-IFN/RBV (total treatment duration of 24 weeks).
TVR (12 Weeks), MCB (24 Weeks), PEG-IFN/RBV (24 Weeks)TelaprevirTwelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with MCB and PEG-IFN/RBV (total treatment duration of 24 weeks).
TVR (12 Weeks), MCB (24 Weeks), PEG-IFN/RBV (48 Weeks)RibavirinTwelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with MCB and PEG-IFN/RBV and then 12 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks).
TVR, MCB, Placebo MCB( each for 12Weeks),PEG-IFN/RBV(48 Weeks)TelaprevirTwelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with placebo matching to MCB and PEG-IFN/RBV, and then 24 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks).
TVR, MCB, Placebo MCB( each for 12Weeks),PEG-IFN/RBV(48 Weeks)Peginterferon Alfa-2aTwelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with placebo matching to MCB and PEG-IFN/RBV, and then 24 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks).
TVR, MCB, Placebo MCB( each for 12Weeks),PEG-IFN/RBV(48 Weeks)RibavirinTwelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with placebo matching to MCB and PEG-IFN/RBV, and then 24 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks).
TVR(12 Weeks), Placebo MCB (24 Weeks), PEG-IFN/RBV(48 Weeks)RibavirinTwelve weeks of therapy with placebo matching to MCB, TVR, PEG-IFN/RBV, will be followed by 12 weeks of therapy with placebo matching to MCB along with PEG-IFN/RBV , following 24 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks).
TVR(12 Weeks), Placebo MCB (24 Weeks), PEG-IFN/RBV(48 Weeks)Peginterferon Alfa-2aTwelve weeks of therapy with placebo matching to MCB, TVR, PEG-IFN/RBV, will be followed by 12 weeks of therapy with placebo matching to MCB along with PEG-IFN/RBV , following 24 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks).
TVR(12 Weeks), Placebo MCB (24 Weeks), PEG-IFN/RBV(48 Weeks)TelaprevirTwelve weeks of therapy with placebo matching to MCB, TVR, PEG-IFN/RBV, will be followed by 12 weeks of therapy with placebo matching to MCB along with PEG-IFN/RBV , following 24 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks).
TVR (12 Weeks), MCB (24 Weeks), PEG-IFN/RBV (48 Weeks)MericitabineTwelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with MCB and PEG-IFN/RBV and then 12 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks).
TVR, MCB, Placebo MCB( each for 12Weeks),PEG-IFN/RBV(48 Weeks)MericitabineTwelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with placebo matching to MCB and PEG-IFN/RBV, and then 24 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks).
Primary Outcome Measures
NameTimeMethod
Percent of Participants With Sustained Virological Response 12 Weeks After End of Treatment (SVR12), as Determined by Polymerase Chain Reaction (PCR) Using Roche COBAS TaqMan Hepatitis C Virus (HCV) Test12 weeks after end of treatment (up to Week 60)
Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Treatment- Resistant Mutations, as Determined Using Standard Sequencing TechnologyBaseline up to Week 60
Change From Baseline in HCV Ribonucleic Acid (RNA) LevelsBaseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, 52, 60, and 72
Trough Concentration of RO4995855 (Parent Drug of Mericitabine)Pre-dose (-0.5 hour) on Day 1 and Week 8; 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hour post dose in Week 8
Percentage of Participants With Adverse EventBaseline up to Week 72
Trough Concentration of TelaprevirPre-dose (-0.5 hour) on Day 1 and Week 8; 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hour post dose in Week 8
Percentage of Participants With Sustained Virological Response 4 Weeks After End of Treatment (SVR-4), as Determined by PCR Using Roche COBAS TaqMan HCV Test4 weeks after end of treatment (up to Week 52)
Percentage of Participants With Virological Response Over Time From Week 2 to Week 48, as Determined by PCR Using Roche COBAS TaqMan HCV TestWeeks 2, 4, 12, 24, and 48
Percentage of Participants With Sustained Virological Response 24 Weeks After End of Treatment (SVR-24), as Determined by PCR Using Roche COBAS TaqMan HCV Test24 weeks after end of treatment (up to Week 72)
Trough Concentration of Metabolite of RO4995855 (RO5012433)Pre-dose (-0.5 hour) on Day 1 and Week 8; 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hour post dose in Week 8

Trial Locations

Locations (39)

Carolina'S Center For Liver Disease

🇺🇸

Statesville, North Carolina, United States

Harborview Medical Center

🇺🇸

Seattle, Washington, United States

Birmingham Gastro Associates, P.C.

🇺🇸

Birmingham, Alabama, United States

Baylor Uni Medical Center; Division Of Hepatology/Transplantation; Annette C. and Harold C. Simmons

🇺🇸

Dallas, Texas, United States

Gordon & Leslie Diamond Health Care Centre; Dept. of Medicine - Division of Gastroenterology

🇨🇦

Vancouver, British Columbia, Canada

Winnipeg Regional Health Authority; Section of Hepatology

🇨🇦

Winnipeg, Manitoba, Canada

GI Research Institute; Gastroenterology & Hepatology

🇨🇦

Vancouver, British Columbia, Canada

Percuro Clinical Research Ltd.

🇨🇦

Victoria, British Columbia, Canada

Weill Cornell Medical College

🇺🇸

New York, New York, United States

Yale University

🇺🇸

New Haven, Connecticut, United States

McGill University, Montreal Chest Institute; Viral and other Infectious

🇨🇦

Montreal, Quebec, Canada

VA Long Beach Healthcare System

🇺🇸

Long Beach, California, United States

UCSD Antiviral Research Center

🇺🇸

San Diego, California, United States

Gastroenterology Group of Naples

🇺🇸

Naples, Florida, United States

John Hopkins Hospital

🇺🇸

Lutherville, Maryland, United States

Kaiser Permanente Sacramento Medical Center

🇺🇸

Sacramento, California, United States

Metrowest Medical Center

🇺🇸

Framingham, Massachusetts, United States

Uni of Cincinnati College of Medicine; Div. of Digestive Diseases

🇺🇸

Cincinnati, Ohio, United States

Toronto Digest. Disease Asso.

🇨🇦

Woodbridge, Ontario, Canada

McGuire; Veteran Affairs Med Ctr

🇺🇸

Richmond, Virginia, United States

Hopital Claude Huriez;Gastro Enterologie

🇫🇷

Lille, France

Fondation Hopital Saint Joseph; Gastro-Enterologie

🇫🇷

Marseille, France

University Health Network - Toronto Western Hospital; Hepatology

🇨🇦

Toronto, Ontario, Canada

Hospital Universitario de Canarias; Servicio de Digestivo

🇪🇸

La Laguna, Tenerife, Spain

Hopital Purpan;Gastro Enterologie Hepatologie

🇫🇷

Toulouse, France

UNI DEGLI STUDI - POLICLINICA S. ORSOLA; Dipartimento Malattie dell'Apparato Digerente e Medicina In

🇮🇹

Bologna, Emilia-Romagna, Italy

Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik I

🇩🇪

Frankfurt Am Main, Germany

Uniklinik Freiburg; Abteilung Innere Medizin II

🇩🇪

Freiburg, Germany

Ospedale Cisanello - Az. Osp. Pisana; Unità Operativa Di Gastroenterologia Ed Epatologia

🇮🇹

Pisa, Toscana, Italy

Universitäts Klinikum; Schleswig-Holstein Kiel

🇩🇪

Kiel, Germany

ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Divisione Malattie Infettive

🇮🇹

Milano, Lombardia, Italy

Hospital Universitari Vall d'Hebron; Departamento de Enfermedades Infecciosas

🇪🇸

Barcelona, Spain

Hospital Clinic I Provincial; Servicio de Digestivo

🇪🇸

Barcelona, Spain

Royal Bournemouth Hospital, Gastroenterology

🇬🇧

Dorset, United Kingdom

Imperial College Healthcare NHS Trust; Hepatology Clinical Research Facility

🇬🇧

London, United Kingdom

St George's Hospital

🇬🇧

London, United Kingdom

King'S College Hospital; Institute of Liver Studies

🇬🇧

London, United Kingdom

Saint Louis University Gastroenterology & Hepatology; Clinical Research Unit

🇺🇸

Saint Louis, Missouri, United States

Hospital Carlos III; Laboratorio de Biologia Molecular

🇪🇸

Madrid, Spain

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