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

A Phase II, Randomized, Double-Blind, Multicenter, Parallel Group Study to Evaluate the Sustained Virologic Response of the HCV Polymerase Inhibitor Prodrug RO5024048 in Combination With Telaprevir and Pegasys®/Copegus® in Patients With Chronic Hepatitis C Genotype 1 Virus Infection Who Were Prior Null Responders to Treatment With Pegylated Interferon/Ribavirin

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Ribavirin; Drug: Mericitabine; Drug: Peginterferon Alfa-2a; Drug: Telaprevir; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Gordon & Leslie Diamond Health Care Centre; Dept. of Medicine - Division of Gastroenterology
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • GI Research Institute; Gastroenterology & Hepatology
    • Victoria, British Columbia, Canada, V8V 3P9
      • PerCuro Clinical Research Ltd.
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Winnipeg Regional Health Authority; Section of Hepatology
  • Ontario
    • Toronto, Ontario, Canada, M5G 1L7
      • University Health Network - Toronto Western Hospital; Hepatology
    • Woodbridge, Ontario, Canada, L4L 4Y7
      • Toronto Digest. Disease Asso.
  • Quebec
    • Montreal, Quebec, Canada, H2X2P4
      • McGill University, Montreal Chest Institute; Viral and other Infectious
• France
  • Lille, France, 59037
    • Hopital Claude Huriez;Gastro Enterologie
  • Marseille, France, 13285
    • Fondation Hopital Saint Joseph; Gastro-Enterologie
  • Toulouse, France, 31059
    • Hopital Purpan;Gastro Enterologie Hepatologie
• Germany
  • Frankfurt Am Main, Germany, 60590
    • Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik I
  • Freiburg, Germany, 79106
    • Uniklinik Freiburg; Abteilung Innere Medizin II
  • Kiel, Germany, 24105
    • Universitäts Klinikum; Schleswig-Holstein Kiel
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • UNI DEGLI STUDI - POLICLINICA S. ORSOLA; Dipartimento Malattie dell'Apparato Digerente e Medicina In
  • Lombardia
    • Milano, Lombardia, Italy, 20162
      • ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Divisione Malattie Infettive
  • Toscana
    • Pisa, Toscana, Italy, 56124
      • Ospedale Cisanello - Az. Osp. Pisana; Unità Operativa Di Gastroenterologia Ed Epatologia
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Departamento de Enfermedades Infecciosas
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial; Servicio de Digestivo
  • Madrid, Spain, 28029
    • Hospital Carlos III; Laboratorio de Biologia Molecular
  • Tenerife
    • La Laguna, Tenerife, Spain, 38320
      • Hospital Universitario de Canarias; Servicio de Digestivo
• United Kingdom
  • Dorset, United Kingdom, BH7 7DW
    • Royal Bournemouth Hospital, Gastroenterology
  • London, United Kingdom, SW17 0QT
    • St George's Hospital
  • London, United Kingdom, SE5 9RS
    • King'S College Hospital; Institute of Liver Studies
  • London, United Kingdom, W2 1NY
    • Imperial College Healthcare NHS Trust; Hepatology Clinical Research Facility
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Birmingham Gastro Associates, P.C.
  • California
    • Long Beach, California, United States, 90822
      • VA Long Beach Healthcare System
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Sacramento Medical Center
    • San Diego, California, United States, 92103
      • UCSD Antiviral Research Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • Florida
    • Naples, Florida, United States, 34102
      • Gastroenterology Group Of Naples
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • John Hopkins Hospital
  • Massachusetts
    • Framingham, Massachusetts, United States, 01702
      • MetroWest Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University Gastroenterology & Hepatology; Clinical Research Unit
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • North Carolina
    • Statesville, North Carolina, United States, 28677
      • Carolina'S Center For Liver Disease
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0595
      • Uni of Cincinnati College of Medicine; Div. of Digestive Diseases
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Uni Medical Center; Division Of Hepatology/Transplantation; Annette C. and Harold C. Simmons
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire; Veteran Affairs Med Ctr
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center

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:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TVR (12 Weeks), MCB (24 Weeks), PEG-IFN/RBV (24 Weeks); Twelve 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).	Drug: Ribavirin; Participants will receive a total daily dose of 1000 milligrams (mg) (for participants weighing less than [<] 75 kg) or 1200 mg (for participants weighing greater than or equal to [>=] 75 kg) orally for 24 or 48 weeks.; Other Names: Copegus; Drug: Mericitabine; Participants will receive mericitabine 1000 mg orally twice daily.; Drug: Peginterferon Alfa-2a; Participants will receive 180 micrograms (mcg) subcutaneous injection once weekly.; Other Names: Pegasys; Drug: Telaprevir; Participants will receive telaprevir 750 mg orally three times daily.
Experimental: TVR (12 Weeks), MCB (24 Weeks), PEG-IFN/RBV (48 Weeks); Twelve 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).	Drug: Ribavirin; Participants will receive a total daily dose of 1000 milligrams (mg) (for participants weighing less than [<] 75 kg) or 1200 mg (for participants weighing greater than or equal to [>=] 75 kg) orally for 24 or 48 weeks.; Other Names: Copegus; Drug: Mericitabine; Participants will receive mericitabine 1000 mg orally twice daily.; Drug: Peginterferon Alfa-2a; Participants will receive 180 micrograms (mcg) subcutaneous injection once weekly.; Other Names: Pegasys; Drug: Telaprevir; Participants will receive telaprevir 750 mg orally three times daily.
Experimental: TVR, MCB, Placebo MCB( each for 12Weeks),PEG-IFN/RBV(48 Weeks); Twelve 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).	Drug: Ribavirin; Participants will receive a total daily dose of 1000 milligrams (mg) (for participants weighing less than [<] 75 kg) or 1200 mg (for participants weighing greater than or equal to [>=] 75 kg) orally for 24 or 48 weeks.; Other Names: Copegus; Drug: Mericitabine; Participants will receive mericitabine 1000 mg orally twice daily.; Drug: Peginterferon Alfa-2a; Participants will receive 180 micrograms (mcg) subcutaneous injection once weekly.; Other Names: Pegasys; Drug: Telaprevir; Participants will receive telaprevir 750 mg orally three times daily.; Drug: Placebo; Participants will receive placebo matching to mericitabine orally twice daily.
Active Comparator: TVR(12 Weeks), Placebo MCB (24 Weeks), PEG-IFN/RBV(48 Weeks); Twelve 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).	Drug: Ribavirin; Participants will receive a total daily dose of 1000 milligrams (mg) (for participants weighing less than [<] 75 kg) or 1200 mg (for participants weighing greater than or equal to [>=] 75 kg) orally for 24 or 48 weeks.; Other Names: Copegus; Drug: Peginterferon Alfa-2a; Participants will receive 180 micrograms (mcg) subcutaneous injection once weekly.; Other Names: Pegasys; Drug: Telaprevir; Participants will receive telaprevir 750 mg orally three times daily.; Drug: Placebo; Participants will receive placebo matching to mericitabine orally twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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) Test	12 weeks after end of treatment (up to Week 60)

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Sustained Virological Response 4 Weeks After End of Treatment (SVR-4), as Determined by PCR Using Roche COBAS TaqMan HCV Test	4 weeks after end of treatment (up to Week 52)
Percentage of Participants With Sustained Virological Response 24 Weeks After End of Treatment (SVR-24), as Determined by PCR Using Roche COBAS TaqMan HCV Test	24 weeks after end of treatment (up to Week 72)
Percentage of Participants With Virological Response Over Time From Week 2 to Week 48, as Determined by PCR Using Roche COBAS TaqMan HCV Test	Weeks 2, 4, 12, 24, and 48
Percentage of Participants With Treatment- Resistant Mutations, as Determined Using Standard Sequencing Technology	Baseline up to Week 60
Change From Baseline in HCV Ribonucleic Acid (RNA) Levels	Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, 52, 60, and 72
Percentage of Participants With Adverse Event	Baseline up to Week 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
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
Trough Concentration of Telaprevir	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Wedemeyer H, Forns X, Hezode C, Lee SS, Scalori A, Voulgari A, Le Pogam S, Najera I, Thommes JA. Mericitabine and Either Boceprevir or Telaprevir in Combination with Peginterferon Alfa-2a plus Ribavirin for Patients with Chronic Hepatitis C Genotype 1 Infection and Prior Null Response: The Randomized DYNAMO 1 and DYNAMO 2 Studies. PLoS One. 2016 Jan 11;11(1):e0145409. doi: 10.1371/journal.pone.0145409. eCollection 2016.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2011
• Primary Completion (Actual): January 31, 2014
• Study Completion (Actual): January 31, 2014

Study Registration Dates

• First Submitted: November 28, 2011
• First Submitted That Met QC Criteria: November 28, 2011
• First Posted (Estimate): November 30, 2011

Study Record Updates

• Last Update Posted (Actual): April 24, 2017
• Last Update Submitted That Met QC Criteria: April 21, 2017
• Last Verified: April 1, 2017

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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Peginterferon alfa-2a
• Other Study ID Numbers: NV27779; 2011-002715-28 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No