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

NCT ID: NCT01288209

Last Updated: 2014-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2012-09-30

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.

Detailed Description

This is a randomized (study drug assigned by chance), 2-arm, open-label study to evaluate the efficacy and safety of TMC435 (also referred to as jnj-38733214-aaa) in combination with the standard of care (SoC) therapy consisting of peginterferon alfa-2a (PegIFNα-2a ) and ribavirin (RBV) administered according to the manufacturer's prescribing information in adult, genotype 1 hepatitis C virus (HCV)-infected participants who failed to respond to previous interferon (IFN)-based therapy in Japan. The study objective is to evaluate the efficacy of TMC435 by the proportion of participants with undetectable HCV ribonucleic acid (RNA). Participants will receive 12 weeks of treatment with TMC435 (100 mg) once daily plus PegIFNα-2a (P) and RBV P) followed by 12 or 36 weeks of treatment with PR OR participants will receive 24 weeks of treatment with TMC435 (100 mg) once daily plus PR followed by 24 weeks of treatment with PR. TMC435 is a 100-mg capsule and will be taken orally (via the mouth). Treatment with PR will last 24 or 48 weeks: Pegylated interferon is supplied as a vial containing 1.0 mL solution with 180 mcg PegIFNα-2a and will be injected by a syringe under the skin once weekly. Ribavirin is given as 200-mg tablets (daily dose: 600-1000 mg based on body weight), and taken orally by mouth two times a day after meals. Participants will receive oral capsules of TMC435 (100 mg) once daily up to Week 12 or 24.

Conditions

Hepatitis C, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TMC435 100 mg 12 Wks + PR24/48

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.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

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

Peginterferon alfa-2a (PegIFNα-2a )

Intervention Type: 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.

Ribavirin (RBV)

Intervention Type: 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.

TMC435 100 mg 24 Wks + PR24/48

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.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

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

Peginterferon alfa-2a (PegIFNα-2a )

Intervention Type: 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.

Ribavirin (RBV)

Intervention Type: 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.

Interventions

TMC435

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

Intervention Type: DRUG

Peginterferon alfa-2a (PegIFNα-2a )

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.

Intervention Type: DRUG

Ribavirin (RBV)

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.

Intervention Type: DRUG

Other Intervention Names

PEGASYS; COPEGUS

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Pharmaceutical K.K.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Pharmaceutical K.K. Clinical Trial

Role: STUDY_DIRECTOR

Janssen Pharmaceutical K.K.

Locations

Amagasaki, , Japan

Ichikawa, , Japan

Kagoshima, , Japan

Kanazawa, , Japan

Kawasaki, , Japan

Kitakyushu, , Japan

Kumamoto, , Japan

Kurume, , Japan

Kyoto, , Japan

Matsumoto, , Japan

Musashino, , Japan

Nishinomiya, , Japan

Osaka, , Japan

Ōsaka-sayama, , Japan

Sakai, , Japan

Sapporo, , Japan

Suita, , Japan

Tokyo, , Japan

Yokohama, , Japan

Countries

Japan

Other Identifiers

TMC435HPC3004

Identifier Type: OTHER

Identifier Source: secondary_id

CR017689

Identifier Type: -

Identifier Source: org_study_id