A Study of TMC435350 Administered With or Without Standard of Care Therapy in Participants With Genotype 1 Hepatitis C Virus Infection

NCT ID: NCT00561353

Last Updated: 2014-05-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 121 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2010-05-31

Brief Summary

The purpose of this study is to investigate how efficient TMC435350 will work against the Hepatitis C virus genotype 1 (genotypes refer to the genetic constitution of the virus) and what the concentrations of TMC435350 in the blood are with or without pegylated interferon alpha-2a (PegIFNa-2a) or PegIFNa-2a plus ribavirin.

Detailed Description

This is a blinded (participant and study staff will not know the identity of assigned treatments), randomized (participants assigned to treatment by chance), placebo-controlled (a term used to describe a method of research in which an inactive substance referred to as a placebo is given to one group of participants, while the treatment being tested is given to another group) study to assess the effectiveness, safety, tolerability, and pharmacokinetics (to test the concentration of study drug in the blood over time) of different dose regimens of TMC435350 (hereafter referred to as TMC435) given alone or in combination with peginterferon alpha-2a (PegIFNa-2a) and ribavirin. TMC435 is a new drug that is development for the treatment of Hepatitis C virus (HCV) infection and belongs to a class of drugs that work by blocking an enzyme (protease) that the HCV needs to replicate. The combination of PegIFNa-2a and ribavirin are current standard of care (SoC) therapy for patients with chronic HCV infection. Approximately 72 participants with HCV infection who have never been treated for HCV infection (referred to as treatment-naïve participants) and 36 participants who have been treated for HCV infection (referred to as treatment-experienced participants) who did not respond to previous therapy with interferon (IFN) and who did not discontinue previous anti-HCV therapy because of adverse events [AEs]) will be included in this study. Two blinded placebo-controlled groups (referred to as "cohorts") of treatment-naïve participants will be sequentially initiated TMC435 to ensure that a higher dose is only administered if the previous lower dose is found safe and tolerable. The first group (Cohort 1) of treatment-naïve participants will receive low-doses of TMC435 or placebo for 7 days followed by 21 days of combined tritherapy with PegIFNa-2a and ribavirin OR participants will receive 28 days of tritherapy (TMC435 or placebo + PegIFNa-2a and ribavirin). After review of data from Cohort 1, a second group (Cohort 2) of treatment-naïve participants will be given higher doses of TMC435 or placebo in the same manner described for the first cohort. A third group (Cohort 3) of participants previously planned in the study will not be enrolled. After review of data from Cohort 2, a fourth group (Cohort 4) of treatment-experienced participants will be given 28 days of TMC435 (or placebo) as tritherapy with PegIFNa-2a and ribavirin to determine the maximum tolerated dose of TMC435. In addition, up to 10 HCV-infected individuals (who participated in study TMC435350-TiDP16-C101 (ClinicalTrials.gov registry number NCT00938899) will comprise Cohort 5 and will be given 28 days of TMC435 at a dose previously determined to be safe and efficacious as tritherapy with PegIFNa-2a and ribavirin. Blood samples will be taken from participants at protocol-specified time points to determine plasma concentrations of TMC435 and ribavirin and safety will be monitored throughout the study. Individuals will participate in this study for up 54 weeks (includes up to 6 weeks during the screening period followed by up to 4 weeks of study treatment with TMC435 (or placebo) and up to a maximum of 44 weeks of treatment with PegIFNa-2a and ribavirin.

Conditions

Hepatitis C, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

TMC435 25 mg (Cohort 1/Panel A and B)

Treatment-naïve participants received TMC435 25 mg once daily for 7 days followed by TMC435 25 mg once daily coadministered with peginterferon alpha-2a (PegIFNα-2a) (P) and ribavirin (R) for 21 days (Panel A) OR TMC435 25 mg once daily coadministered with PR for 28 days (Panel B).

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

TMC435 25 mg, 75 mg, 150 mg, or 200 mg capsules taken orally (by mouth) once daily for 21 or 28 days.

Peginterferon (PegIFNα-2a)

Intervention Type: DRUG

One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22

Ribavirin

Intervention Type: DRUG

200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.

TMC435 75mg (Cohort 1/Panel A and B)

Treatment-naïve participants received TMC435 75 mg once daily for 7 days followed by TMC435 75 mg once daily for 21 days with PegIFNα-2a (P) and ribavirin (R) OR TMC435 75 mg once daily coadministered with PR for 28 days (Panel B).

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

TMC435 25 mg, 75 mg, 150 mg, or 200 mg capsules taken orally (by mouth) once daily for 21 or 28 days.

Peginterferon (PegIFNα-2a)

Intervention Type: DRUG

One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22

Ribavirin

Intervention Type: DRUG

200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.

Placebo (Cohort 1/Panel A and B)

Treatment-naïve participants received placebo (identical in appearance to TMC435 25/75 mg) once daily for 7 days followed by placebo once daily coadministered with PegIFNα-2a (P) and ribavirin (R) for 21 days (Panel A) OR and Placebo once daily coadministered with PR for 28 days (Panel B).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsules identical in appearance to TMC435 capsules taken orally (by mouth) once daily for 28 days.

Peginterferon (PegIFNα-2a)

Intervention Type: DRUG

One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22

Ribavirin

Intervention Type: DRUG

200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.

TMC435 200 mg (Cohort 2, Panel A and B)

Treatment-naïve participants received TMC435 200 mg once daily for 7 days followed by TMC435 200 mg once daily coadministered with PegIFNα-2a (P) and ribavirin (R) for 21 days (Panel A) OR TMC435 200 mg once daily coadministered with PR for 28 days (Panel B).

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

TMC435 25 mg, 75 mg, 150 mg, or 200 mg capsules taken orally (by mouth) once daily for 21 or 28 days.

Peginterferon (PegIFNα-2a)

Intervention Type: DRUG

One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22

Ribavirin

Intervention Type: DRUG

200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.

Placebo (Cohort 2/Panel A and B)

Treatment-naïve participants received placebo (identical in appearance to TMC435 200 mg) once daily for 7 days followed by placebo once daily coadministered with PegIFNα-2a (P) and ribavirin (R) for 21 days (Panel A) OR placebo once daily coadministered with PR for 28 days (Panel B).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsules identical in appearance to TMC435 capsules taken orally (by mouth) once daily for 28 days.

Peginterferon (PegIFNα-2a)

Intervention Type: DRUG

One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22

Ribavirin

Intervention Type: DRUG

200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.

TMC435 75 mg (Cohort 4/Panel C)

Treatment-experienced non-responders received TMC435 75 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

TMC435 25 mg, 75 mg, 150 mg, or 200 mg capsules taken orally (by mouth) once daily for 21 or 28 days.

Peginterferon (PegIFNα-2a)

Intervention Type: DRUG

One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22

Ribavirin

Intervention Type: DRUG

200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.

TMC435 150 mg (Cohort 4/Panel C)

Treatment-experienced non-responders received TMC435 150 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

TMC435 25 mg, 75 mg, 150 mg, or 200 mg capsules taken orally (by mouth) once daily for 21 or 28 days.

Peginterferon (PegIFNα-2a)

Intervention Type: DRUG

One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22

Ribavirin

Intervention Type: DRUG

200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.

TMC435 200 mg (Cohort 4/Panel C)

Treatment-experienced non-responders received TMC435 200 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

TMC435 25 mg, 75 mg, 150 mg, or 200 mg capsules taken orally (by mouth) once daily for 21 or 28 days.

Peginterferon (PegIFNα-2a)

Intervention Type: DRUG

One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22

Ribavirin

Intervention Type: DRUG

200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.

Placebo (Cohort 4/Panel C)

Treatment-experienced non-responders received placebo once daily coadministered with PegIFNα-2a and ribavirin for 28 days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsules identical in appearance to TMC435 capsules taken orally (by mouth) once daily for 28 days.

Peginterferon (PegIFNα-2a)

Intervention Type: DRUG

One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22

Ribavirin

Intervention Type: DRUG

200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.

TMC435 200 mg (Cohort 5/Panel D)

Treatment-experienced relapsers received TMC435 200 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

TMC435 25 mg, 75 mg, 150 mg, or 200 mg capsules taken orally (by mouth) once daily for 21 or 28 days.

Peginterferon (PegIFNα-2a)

Intervention Type: DRUG

One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22

Ribavirin

Intervention Type: DRUG

200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.

Interventions

TMC435

TMC435 25 mg, 75 mg, 150 mg, or 200 mg capsules taken orally (by mouth) once daily for 21 or 28 days.

Intervention Type: DRUG

Placebo

Placebo capsules identical in appearance to TMC435 capsules taken orally (by mouth) once daily for 28 days.

Intervention Type: DRUG

Peginterferon (PegIFNα-2a)

One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22

Intervention Type: DRUG

Ribavirin

200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.

Intervention Type: DRUG

Other Intervention Names

PEGASYS; COPEGUS

Eligibility Criteria

Inclusion Criteria

Inclusion Criteria: - Documented chronic genotype 1 Hepatitis C infection - Able to comply with the protocol requirements and having good accessible veins - Amount of virus in the blood (HCV RNA) >= 10.

Exclusion Criteria

000 IU/mL, at screening - Bodyweight as defined by a Quetelet Index (Body Mass Index [BMI]) between 18 and 32 kg/m², extremes included Exclusion Criteria: - Evidence of liver cirrhosis or decompensated liver disease or any other form of non-viral hepatitis - Participants receiving or having received treatment with polymerase inhibitor or protease inhibitor, or Standard of Care therapy with COPEGUS (ribavirin) and PEGASYS (peginterferon alpha-2a) for treatment for HCV during the 6 months before screening - Male participants with female partners of childbearing potential not agreeing to use a reliable birth control method, Female, except if postmenopausal for over 2 years, or posthysterectomy, or post-tubal ligation (without reversal operation) - History or evidence of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, which would compromise the participant 's safety and/or compliance. A positive urine drug test at screening. Urine will be tested to check the current use of amphetamines, cocaine, and opioids (with the exclusion of methadone) - Participants having at least one lab toxicity that is found to be clinically significant - Participants co-infected with HIV, or Hepatitis A or B, or hepatitis B surface antigen, or active tuberculosis at screening, participants with prolonged QTc (>480 ms) value or any cardiac disease at screening, or any active clinically significant disease (e.g., cardiac dysfunction, cardio(myo)pathy, cardiac insufficiency), or medical history or physical examination findings during screening that, in the Investigator's opinion, would compromise the outcome of the trial - Participants having uncontrolled/unstable diabetes, epilepsy, a manifest psychiatric disease, non-stable methadone (or equivalent drug) use or participants having any other unstable disease, participants enrolled in another clinical trial within 90 days prior to screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tibotec Pharmaceuticals, Ireland

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tibotec Pharmaceuticals, Ireland Clinical Trial

Role: STUDY_DIRECTOR

Tibotec Pharmaceuticals, Ireland

Locations

Bruges, , Belgium

Brussels, , Belgium

Edegem, , Belgium

Ghent, , Belgium

Clichy, , France

Lyon, , France

Marseille, , France

Paris, , France

Pessac, , France

Vandœuvre-lès-Nancy, , France

Berlin, , Germany

Düsseldorf, , Germany

Freiburg im Breisgau, , Germany

Hamburg, , Germany

Hanover, , Germany

Kiel, , Germany

München, , Germany

Amsterdam-Zuidoost, , Netherlands

Bialystok, , Poland

Kielce, , Poland

Lodz, , Poland

Warsaw, , Poland

London, , United Kingdom

Plymouth, , United Kingdom

Countries

Belgium; France; Germany; Netherlands; Poland; United Kingdom

References

Benguigui L, Le Gouzouguec S, Balanca B, Ristovski M, Putet G, Butin M, Guillois B, Beissel A. A Customizable Digital Cognitive Aid for Neonatal Resuscitation: A Simulation-Based Randomized Controlled Trial. Simul Healthc. 2024 Oct 1;19(5):302-308. doi: 10.1097/SIH.0000000000000790. Epub 2024 Apr 8.

Reference Type: DERIVED

PMID: 38587329 (View on PubMed)

Lenz O, de Bruijne J, Vijgen L, Verbinnen T, Weegink C, Van Marck H, Vandenbroucke I, Peeters M, Simmen K, Fanning G, Verloes R, Picchio G, Reesink H. Efficacy of re-treatment with TMC435 as combination therapy in hepatitis C virus-infected patients following TMC435 monotherapy. Gastroenterology. 2012 Nov;143(5):1176-1178.e6. doi: 10.1053/j.gastro.2012.07.117. Epub 2012 Aug 8.

Reference Type: DERIVED

PMID: 22885330 (View on PubMed)

Manns M, Reesink H, Berg T, Dusheiko G, Flisiak R, Marcellin P, Moreno C, Lenz O, Meyvisch P, Peeters M, Sekar V, Simmen K, Verloes R. Rapid viral response of once-daily TMC435 plus pegylated interferon/ribavirin in hepatitis C genotype-1 patients: a randomized trial. Antivir Ther. 2011;16(7):1021-33. doi: 10.3851/IMP1894.

Reference Type: DERIVED

PMID: 22024518 (View on PubMed)

Other Identifiers

TMC435350-TiDP16-C201

Identifier Type: OTHER

Identifier Source: secondary_id

CR012607

Identifier Type: -

Identifier Source: org_study_id

NCT00614185

Identifier Type: -

Identifier Source: nct_alias