A Study of TMC435350 Administered With or Without Standard of Care Therapy in Participants With Genotype 1 Hepatitis C Virus Infection

NCT00561353 | Completed Phase 2 Results DMC

• 2 other identifiers: CR012607TMC435350-TiDP16-C201
• Study Type: interventional
• Target: 121
• Locations: 6 countries
• Sites: 24

Brief Summary

The purpose of this study is to investigate how efficient TMC435350 will work against the Hepatitis C virus genotype 1 (genotypes refer to the genetic constitution of the virus) and what the concentrations of TMC435350 in the blood are with or without pegylated interferon alpha-2a (PegIFNa-2a) or PegIFNa-2a plus ribavirin.

Conditions

Hepatitis C, Chronic

Keywords

Hepatitis C, Chronic; Tibotec; TMC435350-TiDP16-C201; TMC435350-C201; TMC435; PEGASYS (peginterferon alpha-2a, PegIFNα-2a); COPEGUS (ribavirin)

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A)

  The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo as for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection).

  Week 4

• Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B)

  The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection).

  Week 4

• Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)

  The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-experienced participants considered non-responders (defined as participants who achieved less than a 2 log10 IU/mL decline from baseline in plasma HCV RNA levels after 12 weeks of previous interferon \[IFN\]-based therapy \[pegylated or non-pegylated\]) or relapsers (defined as a participant with undetectable plasma HCV RNA at the end of treatment of previous IFN-based therapy and subsequent confirmed detectable plasma HCV RNA levels during follow-up).

  Week 4

Secondary Outcomes (25)

• Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A)

  Day 7

• Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B)

  Day 7

• Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)

  Day 7

• Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A)

  Day 2 or 3, Day 7, and Day 28

• Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B)

  Day 2 or 3, Day 7, and Day 28

Study Arms (10)

TMC435 25 mg (Cohort 1/Panel A and B)

EXPERIMENTAL

Treatment-naïve participants received TMC435 25 mg once daily for 7 days followed by TMC435 25 mg once daily coadministered with peginterferon alpha-2a (PegIFNα-2a) (P) and ribavirin (R) for 21 days (Panel A) OR TMC435 25 mg once daily coadministered with PR for 28 days (Panel B).

Drug: TMC435; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin

TMC435 75mg (Cohort 1/Panel A and B)

EXPERIMENTAL

Treatment-naïve participants received TMC435 75 mg once daily for 7 days followed by TMC435 75 mg once daily for 21 days with PegIFNα-2a (P) and ribavirin (R) OR TMC435 75 mg once daily coadministered with PR for 28 days (Panel B).

Drug: TMC435; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin

Placebo (Cohort 1/Panel A and B)

PLACEBO COMPARATOR

Treatment-naïve participants received placebo (identical in appearance to TMC435 25/75 mg) once daily for 7 days followed by placebo once daily coadministered with PegIFNα-2a (P) and ribavirin (R) for 21 days (Panel A) OR and Placebo once daily coadministered with PR for 28 days (Panel B).

Drug: Placebo; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin

TMC435 200 mg (Cohort 2, Panel A and B)

EXPERIMENTAL

Treatment-naïve participants received TMC435 200 mg once daily for 7 days followed by TMC435 200 mg once daily coadministered with PegIFNα-2a (P) and ribavirin (R) for 21 days (Panel A) OR TMC435 200 mg once daily coadministered with PR for 28 days (Panel B).

Drug: TMC435; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin

Placebo (Cohort 2/Panel A and B)

PLACEBO COMPARATOR

Treatment-naïve participants received placebo (identical in appearance to TMC435 200 mg) once daily for 7 days followed by placebo once daily coadministered with PegIFNα-2a (P) and ribavirin (R) for 21 days (Panel A) OR placebo once daily coadministered with PR for 28 days (Panel B).

Drug: Placebo; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin

TMC435 75 mg (Cohort 4/Panel C)

EXPERIMENTAL

Treatment-experienced non-responders received TMC435 75 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days.

Drug: TMC435; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin

TMC435 150 mg (Cohort 4/Panel C)

EXPERIMENTAL

Treatment-experienced non-responders received TMC435 150 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days.

Drug: TMC435; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin

TMC435 200 mg (Cohort 4/Panel C)

EXPERIMENTAL

Treatment-experienced non-responders received TMC435 200 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days.

Drug: TMC435; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin

Placebo (Cohort 4/Panel C)

PLACEBO COMPARATOR

Treatment-experienced non-responders received placebo once daily coadministered with PegIFNα-2a and ribavirin for 28 days.

Drug: Placebo; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin

TMC435 200 mg (Cohort 5/Panel D)

EXPERIMENTAL

Treatment-experienced relapsers received TMC435 200 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days.

Drug: TMC435; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin

Interventions

TMC435 DRUG

TMC435 25 mg, 75 mg, 150 mg, or 200 mg capsules taken orally (by mouth) once daily for 21 or 28 days.

TMC435 150 mg (Cohort 4/Panel C); TMC435 200 mg (Cohort 2, Panel A and B); TMC435 200 mg (Cohort 4/Panel C); TMC435 200 mg (Cohort 5/Panel D); TMC435 25 mg (Cohort 1/Panel A and B); TMC435 75 mg (Cohort 4/Panel C); TMC435 75mg (Cohort 1/Panel A and B)

Placebo DRUG

Placebo capsules identical in appearance to TMC435 capsules taken orally (by mouth) once daily for 28 days.

Placebo (Cohort 1/Panel A and B); Placebo (Cohort 2/Panel A and B); Placebo (Cohort 4/Panel C)

Peginterferon (PegIFNα-2a) DRUG

One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22

Also known as: PEGASYS

Placebo (Cohort 1/Panel A and B); Placebo (Cohort 2/Panel A and B); Placebo (Cohort 4/Panel C); TMC435 150 mg (Cohort 4/Panel C); TMC435 200 mg (Cohort 2, Panel A and B); TMC435 200 mg (Cohort 4/Panel C); TMC435 200 mg (Cohort 5/Panel D); TMC435 25 mg (Cohort 1/Panel A and B); TMC435 75 mg (Cohort 4/Panel C); TMC435 75mg (Cohort 1/Panel A and B)

Ribavirin DRUG

200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.

Also known as: COPEGUS

Placebo (Cohort 1/Panel A and B); Placebo (Cohort 2/Panel A and B); Placebo (Cohort 4/Panel C); TMC435 150 mg (Cohort 4/Panel C); TMC435 200 mg (Cohort 2, Panel A and B); TMC435 200 mg (Cohort 4/Panel C); TMC435 200 mg (Cohort 5/Panel D); TMC435 25 mg (Cohort 1/Panel A and B); TMC435 75 mg (Cohort 4/Panel C); TMC435 75mg (Cohort 1/Panel A and B)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• Tibotec Pharmaceuticals, Ireland: lead

Study Sites (24)

Unknown Facility

Bruges, Belgium

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Brussels, Belgium

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Edegem, Belgium

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Ghent, Belgium

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Clichy, France

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Lyon, France

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Marseille, France

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Paris, France

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Pessac, France

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Vandœuvre-lès-Nancy, France

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Berlin, Germany

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Düsseldorf, Germany

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Freiburg im Breisgau, Germany

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Hamburg, Germany

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Hanover, Germany

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Kiel, Germany

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München, Germany

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Amsterdam-Zuidoost, Netherlands

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Bialystok, Poland

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Kielce, Poland

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Lodz, Poland

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Warsaw, Poland

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London, United Kingdom

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Plymouth, United Kingdom

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Related Publications (3)

• Benguigui L, Le Gouzouguec S, Balanca B, Ristovski M, Putet G, Butin M, Guillois B, Beissel A. A Customizable Digital Cognitive Aid for Neonatal Resuscitation: A Simulation-Based Randomized Controlled Trial. Simul Healthc. 2024 Oct 1;19(5):302-308. doi: 10.1097/SIH.0000000000000790. Epub 2024 Apr 8.

  PMID: 38587329 DERIVED

• Lenz O, de Bruijne J, Vijgen L, Verbinnen T, Weegink C, Van Marck H, Vandenbroucke I, Peeters M, Simmen K, Fanning G, Verloes R, Picchio G, Reesink H. Efficacy of re-treatment with TMC435 as combination therapy in hepatitis C virus-infected patients following TMC435 monotherapy. Gastroenterology. 2012 Nov;143(5):1176-1178.e6. doi: 10.1053/j.gastro.2012.07.117. Epub 2012 Aug 8.

  PMID: 22885330 DERIVED

• Manns M, Reesink H, Berg T, Dusheiko G, Flisiak R, Marcellin P, Moreno C, Lenz O, Meyvisch P, Peeters M, Sekar V, Simmen K, Verloes R. Rapid viral response of once-daily TMC435 plus pegylated interferon/ribavirin in hepatitis C genotype-1 patients: a randomized trial. Antivir Ther. 2011;16(7):1021-33. doi: 10.3851/IMP1894.

  PMID: 22024518 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Simeprevir; peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Global Clinical Development Manager
• Organization: Jan-Cil France

ClinicalTrialDisclosure@its.jnj.com

Study Officials

• Tibotec Pharmaceuticals, Ireland Clinical Trial

  Tibotec Pharmaceuticals, Ireland

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2007
• First Posted: November 20, 2007
• Study Start: January 1, 2008
• Primary Completion: December 1, 2008
• Study Completion: May 1, 2010
• Last Updated: May 20, 2014
• Results First Posted: February 6, 2014

Record last verified: 2014-05

Locations

BE (4); FR (6); DE (7); PL (4); NL (1); GB (2)