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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 3

Conditions: Hepatitis C, Chronic

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01288209

CR017689

TMC435HPC3004 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 106 patients

Sex: All

Ages: 20 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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106 participants in 2 patient groups

TMC435 100 mg 12 Wks + PR24/48

Experimental group

Description:

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.

Treatment:

Drug: Ribavirin (RBV)

Drug: Peginterferon alfa-2a (PegIFNα-2a )

Drug: TMC435

TMC435 100 mg 24 Wks + PR24/48

Experimental group

Description:

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.

Treatment:

Drug: Ribavirin (RBV)

Drug: Peginterferon alfa-2a (PegIFNα-2a )

Drug: TMC435