A Safety and Effectiveness Study of TMC435 in Chronic, Genotype 1, Hepatitis C Patients Who Failed to Previous Standard Treatment (ASPIRE)

Tibotec Pharmaceutical

Status and phase: Completed; Phase 2

Conditions: Hepatitis C

Treatments: Drug: TMC435; Drug: Peg-IFN-alfa-2a (P); Drug: Placebo; Drug: Ribavirin (R)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00980330

2009-010590-20 (EudraCT Number)

CR016063

TMC435-TiDP16-C206 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to determine the efficacy, safety and tolerability of different regimens of TMC435 with standard treatment compared to standard treatment alone in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who has failed previous treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV).

Full description

The study is a randomized (study drug assigned by chance), double-blind (neither physician nor participant knows the name of the assigned drug), placebo-controlled Phase IIb trial with TMC435 in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who have failed standard treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV). The study will compare the efficacy, tolerability and safety of different regimens with TMC435 combined with standard treatment (Peg-INF-alfa-2a and RBV) versus standard treatment alone. The trial will consist of a screening period of maximum 6 weeks, a 48-week treatment period, and a 24-week follow-up period. Participants will be eligible to enroll in the trial if they failed to respond to a prior course of standard treatment or relapsed following standard treatment. Participants will be randomly assigned to receive TMC435 with standard treatment for 12 weeks followed by standard treatment (plus placebo) for 36 weeks, TMC435 (100 mg or 150 mg once a day) with standard treatment for 24 weeks followed by standard treatment (plus placebo) for 24 weeks, TMC435 (100 mg or 150 mg once a day) with standard treatment for 48 weeks, or a placebo with standard treatment for 48 weeks.

Enrollment: 463 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Must have chronic hepatitis C infection as evidenced by liver biopsy, anti-hepatitis C virus (HCV) and HCV RNA positive
• Must have chronic hepatitis C infection (genotype 1) with HCV RNA level greater than10000 IU/mL
• Patient must have failed at least 1 prior course of peg interferon (Peg-IFN-alfa-2a)/ribavirin (RBV) therapy (standard treatment)
• Must be willing to use 2 effective methods of birth control for up to 7 months after last dose of study medication

Exclusion criteria

• Has an evidence of decompensated liver disease
• Co-infection with any other Hepatitis C virus genotype or co-infection with the human immunodeficiency virus (HIV)
• Has a medical condition which is a contraindication to Peg-INF or RBV therapy
• Have had 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: Quadruple Blind

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463 participants in 7 patient groups, including a placebo group

TMC435 100 mg 12 Wks + PR48

Experimental group

Description:

Participants will receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks.

Treatment:

Drug: Ribavirin (R)

Drug: TMC435

Drug: Placebo

Drug: Peg-IFN-alfa-2a (P)

TMC435 100 mg 24 Wks + PR48

Experimental group

Description:

Participants willl receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks.

Treatment:

Drug: Ribavirin (R)

Drug: TMC435

Drug: Placebo

Drug: Peg-IFN-alfa-2a (P)

TMC435 100 mg 48 Wks + PR48

Experimental group

Description:

Participants will receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.

Treatment:

Drug: Ribavirin (R)

Drug: TMC435

Drug: Placebo

Drug: Peg-IFN-alfa-2a (P)

TMC435 150 mg 12 Wks + PR48

Experimental group

Description:

Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks.

Treatment:

Drug: Ribavirin (R)

Drug: TMC435

Drug: Placebo

Drug: Peg-IFN-alfa-2a (P)

TMC435 150 mg 24 Wks + PR48

Experimental group

Description:

Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks.

Treatment:

Drug: Ribavirin (R)

Drug: TMC435

Drug: Placebo

Drug: Peg-IFN-alfa-2a (P)

TMC435 150 mg 48 Wks + PR48

Experimental group

Description:

Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.

Treatment:

Drug: Ribavirin (R)

Drug: TMC435

Drug: Peg-IFN-alfa-2a (P)

Placebo 48 Wks + PR48

Placebo Comparator group

Description:

Participants will receive Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.

Treatment:

Drug: Ribavirin (R)

Drug: TMC435

Drug: Peg-IFN-alfa-2a (P)