A Study of TMC435 in Combination With Peginterferon Alfa-2A and Ribavirin for Hepatitis C Virus Genotype-1 Infected Patients Who Participated in a Control Group of a TMC435 Study

A Phase III, Open-Label, Single Arm, Rollover Trial of TMC435 in Combination With Peginterferon Alpha-2A and Ribavirin for HCV Genotype-1 Infected Subjects Who Participated in the Placebo Group of a Phase II/III TMC435 Study, or Who Received DAA Treatment in a Tibotec-Sponsored Phase I Study.

The purpose of this study is to investigate the efficacy of a treatment with TMC435 in combination with peginterferon alfa-2a and ribavirin in patients who did not clear their hepatitis C infection with peginterferon alfa-2a and ribavirin alone within a previous trial conducted by Tibotec, or who participated in Tibotec trials in which antivirals directed against hepatitis C virus (HCV) were evaluated for short periods of time.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: TMC435

Detailed Description

This is a roll over trial of TMC435 for patients with genotype-1 HCV infection who participated in the control (placebo; substance containing no active medication) group of a TMC435 trial or who received a treatment for up to 14 days with antivirals directed against HCV in a previous Tibotec trial. Patients in this study will receive TMC435 in combination with peginterferon alfa-2a (Pegasys) and ribavirin (Copegus) followed by peginterferon alfa-2a and ribavirin alone. The total treatment duration will be 24 or 48 weeks, depending on how the patients respond to treatment and which was their previous response to peginterferon alfa-2a and ribavirin alone. The study doctor will inform each patient about how to take their study medication and when they should stop taking it. After a patient stops taking study medication, they will contiue to come to the doctor's office for study visits until 24 weeks (in some cases up to 48 weeks) after end of treatment. The total duration of the study is 78 weeks (including screening). Patients will be monitored for safety throughout the study. Study assessments at each visit may include but are not limited to: blood and urine collection for testing, electrocardiogram (ECG) assessments (a measurement of the electrical activity of the heart) and physical examinations. TMC435 will be taken as an oral capsule of 150 mg once per day. Peginterferon (Pegasys) will be given as an injection of 180 µg once each week. Ribavirin will be taken as tablets (Copegus) twice each day and the dose will depend on patient's body weight.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
  • Rosario, Santa Fe, Argentina
• Australia
  • Adelaide, Australia
  • Concord, Australia
  • Melbourne, Australia
  • Wentworthville, Australia
  • Woolloongabba N/A, Australia
• Austria
  • Wien, Austria
• Belgium
  • Antwerpen, Belgium
  • Brussels, Belgium
  • Gent, Belgium
• Brazil
  • Sao Paulo, Brazil
• Bulgaria
  • Sofia, Bulgaria
• Canada
  • Ontario
    • Toronto, Ontario, Canada
  • Quebec
    • Montreal, Quebec, Canada
• France
  • Grenoble, France
  • Lyon, France
  • Nice Cedex 03 N/A, France
  • Paris Cedex 12, France
• Germany
  • Berlin, Germany
  • Frankfurt A. M., Germany
  • Hamburg, Germany
  • Kiel, Germany
  • Münster, Germany
  • Ulm, Germany
  • Würzburg, Germany
• Israel
  • Haifa, Israel
  • Zefat, Israel
• Mexico
  • Monterrey, Mexico
• Netherlands
  • Amsterdam, Netherlands
  • Rotterdam, Netherlands
• New Zealand
  • Auckland, New Zealand
  • Christchurch, New Zealand
• Poland
  • Bydgoszcz, Poland
  • Chorzów, Poland
  • Czeladz, Poland
  • Kielce, Poland
  • Myslowice, Poland
  • Warschau, Poland
• Portugal
  • Coimbra, Portugal
  • Lisboa, Portugal
• Puerto Rico
  • San Juan, Puerto Rico
• Romania
  • Bucuresti, Romania
• Russian Federation
  • Moscow, Russian Federation
  • Saint-Petersburg, Russian Federation
  • Samara, Russian Federation
  • Smolensk, Russian Federation
  • St Petersburg, Russian Federation
  • Stavropol, Russian Federation
• Spain
  • Barcelona, Spain
  • Madrid, Spain
  • Sevilla N/A, Spain
  • Valencia, Spain
• Ukraine
  • Donetsk, Ukraine
  • Kyiv, Ukraine
  • Vinnitsa, Ukraine
• United Kingdom
  • Birmingham, United Kingdom
  • London, United Kingdom
• United States
  • California
    • Bakersfield, California, United States
    • Los Angeles, California, United States
    • San Diego, California, United States
  • Colorado
    • Englewood, Colorado, United States
  • Florida
    • Jacksonville, Florida, United States
    • Orlando, Florida, United States
  • Louisiana
    • New Orleans, Louisiana, United States
  • Mississippi
    • Jackson, Mississippi, United States
    • Tupelo, Mississippi, United States
  • North Carolina
    • Chapel Hill, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
  • Texas
    • Dallas, Texas, United States
    • Houston, Texas, United States
    • San Antonio, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who participated in the placebo arm of a TMC435 study who did not achieve undetectable HCV RNA levels at end of treatment or who relapsed within 1 year after end of treatment OR Patients who received short-term direct-acting antiviral therapy in a Tibotec-sponsored study.
• Liver disease stage documented by liver biopsy is required within 3 years prior to screening unless contraindicated.

Exclusion Criteria:

• Infection with human immunodeficiency virus.
• Liver disease not related to hepatitic C infection.
• Significant laboratory abnormalities or other active diseases.
• Pregnant or planning to become pregnant.
• Prematurely stopped medication in previous TMC435 study for non-compliance or for safety reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TMC435; TMC435 Type=exact number unit=mg number=150 form=capsule route=oral use once daily for 12 weeks in addition to peginterferon alfa-2a peginterferon and ribavirin for 24 or 48 weeks	Drug: TMC435; Type=exact number, unit=mg, number=150, form=capsule, route=oral use, once daily for 12 weeks in addition to peginterferon alfa-2a peginterferon and ribavirin for 24 or 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of participants with sustained viral response	12 weeks after planned end of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
The proportion of participants with sustained viral response	24 weeks after planned end of treatment
Number of participants with HCV RNA level >1000 IU/mL	Week 4
Number of participants with viral breakthrough	Through Week 48
Number of participants with viral relapse	Through Week 48
Number of participants with normalized alanine aminotransferase levels	Through Week 48
Number of participants with on-treatment failure	Through Week 48
Number of participants affected by an adverse event	Through Week 48

Collaborators and Investigators

• Sponsor: Janssen R&D Ireland

Publications and helpful links

General Publications

• Gane EJ, DeJesus E, Janczewska E, George J, Diago M, Da Silva MH, Reesink H, Nikitin I, Hinrichsen H, Bourgeois S, Ferenci P, Shukla U, Kalmeijer R, Lenz O, Fevery B, Corbett C, Beumont M, Jessner W. Simeprevir with peginterferon alpha-2a/ribavirin for chronic hepatitis C virus genotype 1 infection in treatment-experienced patients: an open-label, rollover study. BMC Infect Dis. 2017 Jun 2;17(1):389. doi: 10.1186/s12879-017-2444-3.

Helpful Links

• A Study of TMC435 in Combination with Peginterferon Alfa-2A and Ribavirin for Hepatitis C Virus Genotype-1 Infected Patients who Participated in a Control Group of a TMC435 Study.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: March 24, 2011
• First Submitted That Met QC Criteria: March 24, 2011
• First Posted (Estimate): March 25, 2011

Study Record Updates

• Last Update Posted (Estimate): April 4, 2016
• Last Update Submitted That Met QC Criteria: March 31, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: HCV; Hepatitis C; TMC435; TMC435-TiDP16-C213; TMC435-C213
• 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; Hepatitis A; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Protease Inhibitors; Simeprevir
• Other Study ID Numbers: CR017983; TMC435-TiDP16-C213 (Other Identifier: Janssen R&D Ireland)