A Phase III Study of TMC435 in Genotype 1, Hepatitis C-infected Participants Who Failed to Respond to Previous IFN-based Therapy

NCT01288209 | Completed Phase 3 Results

• 2 other identifiers: CR017689TMC435HPC3004
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 19

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of TMC435 in combination with peginterferon alfa-2a (PegIFNα-2a) and ribavirin in genotype 1 hepatitis C virus (HCV)-infected participants who failed to respond to previous interferon (IFN)-based therapy in Japan.

Conditions

Hepatitis C, Chronic

Keywords

Hepatitis C, Chronic; Hepatitis C; Hepatitis C virus; Interferon Alfa-2a; Ribavirin; Viral RNA

Outcome Measures

Primary Outcomes (1)

• The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 12 Weeks After the Last Dose of Treatment (SVR12)

  The table below shows the observed percentage of participants in each treatment group with a SVR12 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at the EOT (Week 24 or 48) and at 12 weeks after the last dose of treatment (Week 36 or 60).

  EOT (Week 24 or 48) and Week 36 or 60

Secondary Outcomes (10)

• The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the End of Treatment (EOT) and 24 Weeks After the Last Dose of Treatment (SVR24)

  EOT (Week 24 or 48) and Week 48 or 72

• The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up

  Day 3, Day 7, and Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 48, 60, 72, EOT, and Follow-up (FU) Weeks 4, 12, and 24

• The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)

  Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT

• The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During Treatment for Participants Who Did Not Achieve Undetectable Plasma HCV RNA Levels at Week 12

  Weeks 24, 48, EOT (Weeks 24 or 48), SVR12 (Weeks 36 or 60), and SVR24 (Weeks 48 or 72)

• The Number of Participants With Viral Breakthrough During the Study

  Up to EOT (Week 24 or 48)

Study Arms (2)

TMC435 100 mg 12 Wks + PR24/48

EXPERIMENTAL

Participants will receive TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment will be stopped at Week 24 if participants achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \< 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants will continue PR until Week 48.

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

TMC435 100 mg 24 Wks + PR24/48

EXPERIMENTAL

Participants will receive TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment will be stopped at Week 24 if participants achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \< 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants will continue PR until Week 48.

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

Interventions

TMC435 DRUG

100-mg capsule taken by mouth once daily for 12 or 24 weeks.

TMC435 100 mg 12 Wks + PR24/48; TMC435 100 mg 24 Wks + PR24/48

Peginterferon alfa-2a (PegIFNα-2a ) DRUG

PegIFNα-2a (PEGASYS) will be administered according to the manufacturer's prescribing information as 180 mcg once weekly injected subcutaneous (under the skin) for up to 24-48 weeks.

Also known as: PEGASYS

TMC435 100 mg 12 Wks + PR24/48; TMC435 100 mg 24 Wks + PR24/48

Ribavirin (RBV) DRUG

RBV (COPEGUS) will be administered according to the manufacturer's prescribing information. If body weight is \> 80 kg the total daily dose of RBV will be 1000 mg, taken by mouth as 400 mg (2 tablets of 200 mg) after breakfast and 600 mg (3 tablets of 200 mg) after supper. If body weight is \> 60 kg to \<=80 kg the total daily dose will be 800 mg, taken by mouth as 400 mg (2 tablets of 200 mg per intake) after breakfast and supper. If body weight is \<=60 kg the total daily dose of RBV will be 600 mg, taken by mouth as 200 mg (1 tablet of 200 mg) after breakfast and 400 mg (2 tablets of 200 mg) after supper. Total duration of RBV will be 24-48 weeks.

Also known as: COPEGUS

TMC435 100 mg 12 Wks + PR24/48; TMC435 100 mg 24 Wks + PR24/48

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must have chronic genotype 1 HCV infection with HCV RNA level \>= 5.0 log10 IU/mL
• Participant failed to respond to previous IFN-based therapy
• Participant must be willing to use contraceptive measures from the time of informed consent to 6 months after last dose of study medication.

You may not qualify if:

• Co-infection with any other HCV genotype or co-infection with the human immunodeficiency virus (HIV)
• Diagnosed with hepatic cirrhosis or hepatic failure
• A medical condition which is a contraindication to PegIFNα-2a or ribavirin therapy
• History of, or any current medical condition which could impact the safety of the patient in the study

Sponsors & Collaborators

• Janssen Pharmaceutical K.K.: lead

Study Sites (19)

Unknown Facility

Amagasaki, Japan

Location

Unknown Facility

Ichikawa, Japan

Location

Unknown Facility

Kagoshima, Japan

Location

Unknown Facility

Kanazawa, Japan

Location

Unknown Facility

Kawasaki, Japan

Location

Unknown Facility

Kitakyushu, Japan

Location

Unknown Facility

Kumamoto, Japan

Location

Unknown Facility

Kurume, Japan

Location

Unknown Facility

Kyoto, Japan

Location

Unknown Facility

Matsumoto, Japan

Location

Unknown Facility

Musashino, Japan

Location

Unknown Facility

Nishinomiya, Japan

Location

Unknown Facility

Osaka, Japan

Location

Unknown Facility

Ōsaka-sayama, Japan

Location

Unknown Facility

Sakai, Japan

Location

Unknown Facility

Sapporo, Japan

Location

Unknown Facility

Suita, Japan

Location

Unknown Facility

Tokyo, Japan

Location

Unknown Facility

Yokohama, Japan

Location

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

Simeprevir; peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

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: Manager
• Organization: Janssen Pharmaceutical K.K., Japan

81 3 44115639

Study Officials

• Janssen Pharmaceutical K.K. Clinical Trial

  Janssen Pharmaceutical K.K.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2011
• First Posted: February 2, 2011
• Study Start: February 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: January 24, 2014
• Results First Posted: January 24, 2014

Record last verified: 2013-12

Locations

JP (19)