A Study of TMC435 in Combination With Pegylated Interferon Alp\Fa-2a and Ribavirin in Patients Infected With Genotype 1 Hepatitis C Virus Who Never Received Treatment

NCT00882908 | Completed Phase 2 Results DMC

• 3 other identifiers: CR015799TMC435-TiDP16-C2052008-007147-13
• Study Type: interventional
• Target: 386
• Locations: 12 countries
• Sites: 65

Brief Summary

The purpose of this study is to evaluate the efficacy of 4 different regimens of TMC435 in combination with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV), defined as the proportion of patients with sustained virologic response at Week 72 (patients with undetectable plasma HCV RNA \[less than 25 IU per mL undetectable\] at the end of treatment and at Week 72), compared to the control group receiving PegIFN and RBV in combination with TMC435-matched placebo.

Conditions

Hepatitis C

Keywords

Hepatitis C; TMC435; Peginterferon alpha-2a; PegIFNalpha-2a; RBV; Ribavirin; Placebo

Outcome Measures

Primary Outcomes (1)

• The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)

  The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72.

  Week 72

Secondary Outcomes (13)

• The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Undetectable During Treatment and Follow-up

  Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)

• The Percentage of Participants Who Achieved Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Detectable or Undetectable During Treatment and Follow-up

  Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)

• The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Greater Than or Equal to 2 log10 Drop During Treatment

  Baseline (Day 1) and Weeks, 2, 4, 8, and 12

• The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)

  Week 48 or 72

• The Percentage of Participants Achieving a Rapid Virologic Response (RVR)

  Week 4

Study Arms (5)

TMC435 75 mg 12 Wks + PR 24/48

EXPERIMENTAL

Participants will receive TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

Drug: TMC435; Drug: Ribavirin (R); Drug: PegIFNα-2a (P); Drug: Placebo

TMC435 75 mg 24 Wks + PR 24/48

EXPERIMENTAL

Participants will receive TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

Drug: TMC435; Drug: Ribavirin (R); Drug: PegIFNα-2a (P); Drug: Placebo

TMC435 150 mg 12 Wks + PR 24/48

EXPERIMENTAL

Participants will receive TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

Drug: TMC435; Drug: Ribavirin (R); Drug: PegIFNα-2a (P); Drug: Placebo

TMC435 150 mg 24 Wks + PR 24/48

EXPERIMENTAL

Participants will receive TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

Drug: TMC435; Drug: Ribavirin (R); Drug: PegIFNα-2a (P); Drug: Placebo

Placebo 24 Wks + PR48

PLACEBO COMPARATOR

Participants will receive Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.

Drug: Ribavirin (R); Drug: PegIFNα-2a (P); Drug: Placebo

Interventions

TMC435 DRUG

TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.

Also known as: TMC 435

TMC435 150 mg 12 Wks + PR 24/48; TMC435 150 mg 24 Wks + PR 24/48; TMC435 75 mg 12 Wks + PR 24/48; TMC435 75 mg 24 Wks + PR 24/48

Ribavirin (R) DRUG

Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.

Also known as: COPEGUS

Placebo 24 Wks + PR48; TMC435 150 mg 12 Wks + PR 24/48; TMC435 150 mg 24 Wks + PR 24/48; TMC435 75 mg 12 Wks + PR 24/48; TMC435 75 mg 24 Wks + PR 24/48

PegIFNα-2a (P) DRUG

PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.

Also known as: PEGASYS

Placebo 24 Wks + PR48; TMC435 150 mg 12 Wks + PR 24/48; TMC435 150 mg 24 Wks + PR 24/48; TMC435 75 mg 12 Wks + PR 24/48; TMC435 75 mg 24 Wks + PR 24/48

Placebo DRUG

Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.

Placebo 24 Wks + PR48; TMC435 150 mg 12 Wks + PR 24/48; TMC435 150 mg 24 Wks + PR 24/48; TMC435 75 mg 12 Wks + PR 24/48; TMC435 75 mg 24 Wks + PR 24/48

Eligibility Criteria

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

You may qualify if:

• Patients with documented chronic genotype-1 hepatitis C infection and with plasma HCV RNA of \> 100,000 IU/mL at screening
• Patients that have not been treated before for HCV
• Patients that are of childbearing potential or have a partner of childbearing potential should agree to use 2 effective methods of contraception

You may not qualify if:

• Patients with cirrhosis or evidence of hepatic decompensation
• Co-infection with the human immunodeficiency virus (HIV)
• Any contraindication to Pegasys or Copegus therapy
• History of, or any current medical condition which could impact the safety of the patient in the study

Sponsors & Collaborators

• Tibotec Pharmaceuticals, Ireland: lead

Study Sites (71)

Unknown Facility

Los Angeles, California, United States

Location

Unknown Facility

Jacksonville, Florida, United States

Location

Unknown Facility

Orlando, Florida, United States

Location

Unknown Facility

Palm Harbor, Florida, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

New Orleans, Louisiana, United States

Location

Unknown Facility

Saint Paul, Minnesota, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Chapel Hill, North Carolina, United States

Location

Unknown Facility

Cincinnati, Ohio, United States

Location

Unknown Facility

Germantown, Tennessee, United States

Location

Unknown Facility

Charlottesville, Virginia, United States

Location

Unknown Facility

Concord, Australia

Location

Unknown Facility

Darlinghurst, Australia

Location

Unknown Facility

Fitzroy, Australia

Location

Unknown Facility

Melbourne, Australia

Location

Unknown Facility

Sydney, Australia

Location

Unknown Facility

Woolloongabba, Australia

Location

Unknown Facility

Vienna, Austria

Location

Unknown Facility

Bruges, Belgium

Location

Unknown Facility

Brussels, Belgium

Location

Unknown Facility

Edegem, Belgium

Location

Unknown Facility

Ghent, Belgium

Location

Unknown Facility

Leuven, Belgium

Location

Unknown Facility

Roeselare, Belgium

Location

Unknown Facility

Calgary, Alberta, Canada

Location

Unknown Facility

Toronto, Ontario, Canada

Location

Unknown Facility

Montreal, Quebec, Canada

Location

Unknown Facility

Aarhus, Denmark

Location

Unknown Facility

Copenhagen, Denmark

Location

Unknown Facility

Hvidovre, Denmark

Location

Unknown Facility

Kolding, Denmark

Location

Unknown Facility

Odense, Denmark

Location

Unknown Facility

Clichy, France

Location

Unknown Facility

Créteil, France

Location

Unknown Facility

Grenoble, France

Location

Unknown Facility

Lyon, France

Location

Unknown Facility

Nice, France

Location

Unknown Facility

Paris, France

Location

Unknown Facility

Vandœuvre-lès-Nancy, France

Location

Unknown Facility

Berlin, Germany

Location

Unknown Facility

Cologne, Germany

Location

Unknown Facility

Düsseldorf, Germany

Location

Unknown Facility

Frankfurt A. M., Germany

Location

Unknown Facility

Freiburg im Breisgau, Germany

Location

Unknown Facility

Hamburg, Germany

Location

Unknown Facility

Hanover, Germany

Location

Unknown Facility

Stuttgart, Germany

Location

Unknown Facility

Würzburg, Germany

Location

Unknown Facility

Auckland, New Zealand

Location

Unknown Facility

Christchurch, New Zealand

Location

Unknown Facility

Hamilton, New Zealand

Location

Unknown Facility

Bergen, Norway

Location

Unknown Facility

Nordbyhagen, Norway

Location

Unknown Facility

Oslo, Norway

Location

Unknown Facility

Tromsø, Norway

Location

Unknown Facility

Bialystok, Poland

Location

Unknown Facility

Bydgoszcz, Poland

Location

Unknown Facility

Czeladź, Poland

Location

Unknown Facility

Kielce, Poland

Location

Unknown Facility

Lodz, Poland

Location

Unknown Facility

Warsaw, Poland

Location

Unknown Facility

Moscow, Russia

Location

Unknown Facility

Nizhny Novgorod, Russia

Location

Unknown Facility

Saint Petersburg, Russia

Location

Unknown Facility

Samara, Russia

Location

Unknown Facility

Smolensk, Russia

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Seville, Spain

Location

Unknown Facility

Valencia, Spain

Location

Related Publications (3)

• Lenz O, Verbinnen T, Fevery B, Tambuyzer L, Vijgen L, Peeters M, Buelens A, Ceulemans H, Beumont M, Picchio G, De Meyer S. Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in Phase IIb/III studies. J Hepatol. 2015 May;62(5):1008-14. doi: 10.1016/j.jhep.2014.11.032. Epub 2014 Nov 28.

  PMID: 25445400 DERIVED

• Scott J, Rosa K, Fu M, Cerri K, Peeters M, Beumont M, Zeuzem S, Evon DM, Gilles L. Fatigue during treatment for hepatitis C virus: results of self-reported fatigue severity in two Phase IIb studies of simeprevir treatment in patients with hepatitis C virus genotype 1 infection. BMC Infect Dis. 2014 Aug 26;14:465. doi: 10.1186/1471-2334-14-465.

  PMID: 25164700 DERIVED

• Fried MW, Buti M, Dore GJ, Flisiak R, Ferenci P, Jacobson I, Marcellin P, Manns M, Nikitin I, Poordad F, Sherman M, Zeuzem S, Scott J, Gilles L, Lenz O, Peeters M, Sekar V, De Smedt G, Beumont-Mauviel M. Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naive genotype 1 hepatitis C: the randomized PILLAR study. Hepatology. 2013 Dec;58(6):1918-29. doi: 10.1002/hep.26641. Epub 2013 Oct 11.

  PMID: 23907700 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

Simeprevir; Ribavirin; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

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: GT60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: April 16, 2009
• First Posted: April 17, 2009
• Study Start: June 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2011
• Last Updated: June 16, 2014
• Results First Posted: June 16, 2014

Record last verified: 2014-05

Locations

AU (1); US (12); DK (5); DE (9); NZ (3); FR (7); ES (4); CA (3); BE (6); NO (4); RU (5); PL (6)