TMC435-TiDP16-C206: A Safety and Efficacy Study in Chronic, Genotype 1, Hepatitis C Patients That Failed Previous Standard Treatment - Full Text View

Sponsor:	Tibotec Pharmaceuticals, Ireland
Information provided by:	Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:	NCT00980330

Purpose

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 patients with chronic, genotype 1, hepatitis C who have failed previous treatment with pegylated interferon (Peg-INF) and ribavirin (RBV).

Condition	Intervention	Phase
Hepatitis C	Drug: TMC435 /Peg IFNa2A/Ribavirin TMC435 placebo Drug: TMC435 /Peg IFNa2A/Ribavirin Drug: TMC435 placebo /Peg IFNa2A/Ribavirin	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase IIb, Randomized, Double-blind, Placebo-controlled Trial to Investigate the Efficacy, Tolerability, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including PegIFNa-2a and Ribavirin in HCV Genotype 1 Infected Subjects Who Failed Previous Standard Therapy

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin Peginterferon Alfa-2a

U.S. FDA Resources

Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:

The proportion of patients with undetectable HCV RNA [ Time Frame: 24 weeks after the planned end of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of patients with rapid virologic response (RVR) [ Time Frame: at Week 4 ] [ Designated as safety issue: No ]
Proportion of patients with early virologic response (EVR) and complete early virologic response (cEVR) [ Time Frame: at Week 12 ] [ Designated as safety issue: No ]
Proportion of patients with undetectable HCV-RNA (SVR 12) [ Time Frame: at Week 60 ] [ Designated as safety issue: No ]
Changes in HCV RNA levels over time [ Time Frame: 20 visits over 72-week period ] [ Designated as safety issue: No ]
PK/PD relationship of TMC435 [ Time Frame: at Week 2, 4, 8, 12, 16, 24 and 48 ] [ Designated as safety issue: No ]

Enrollment:	464
Study Start Date:	September 2009
Study Completion Date:	August 2011
Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 004 TMC435 /Peg IFNa2A/Ribavirin TMC435 placebo 24 weeks 150 mg TMC435 / 180 µg injection Peg IFNa2A/ 1000-1200 mg Ribavirin followed by 24 weeks TMC435 placebo /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin	Drug: TMC435 /Peg IFNa2A/Ribavirin TMC435 placebo 12 weeks 100 mg TMC435 / 180 µg injection Peg IFNa2A/ 1000-1200 mg Ribavirin followed by 36 weeks TMC435 placebo /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin
Experimental: 005 TMC435 /Peg IFNa2A/Ribavirin 48 weeks 100 mg TMC435 /180µg injection Peg IFNa2A/1000-1200 mg Ribavirin	Drug: TMC435 /Peg IFNa2A/Ribavirin TMC435 placebo 12 weeks 150 mg TMC435 / 180 µg injection Peg IFNa2A/ 1000-1200 mg Ribavirin followed by 36 weeks TMC435 placebo /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin Drug: TMC435 /Peg IFNa2A/Ribavirin 48 weeks 100 mg TMC435 /180µg injection Peg IFNa2A/1000-1200 mg Ribavirin
Experimental: 006 TMC435 /Peg IFNa2A/Ribavirin 48 weeks 150 mg TMC435 /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin	Drug: TMC435 /Peg IFNa2A/Ribavirin TMC435 placebo 24 weeks 100 mg TMC435 / 180 µg injection Peg IFNa2A/ 1000-1200 mg Ribavirin followed by 24 weeks TMC435 placebo /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin Drug: TMC435 /Peg IFNa2A/Ribavirin 48 weeks 150 mg TMC435 /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin
Active Comparator: 007 TMC435 placebo /Peg IFNa2A/Ribavirin 48 weeks TMC435 placebo /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin	Drug: TMC435 /Peg IFNa2A/Ribavirin TMC435 placebo 24 weeks 150 mg TMC435 / 180 µg injection Peg IFNa2A/ 1000-1200 mg Ribavirin followed by 24 weeks TMC435 placebo /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin Drug: TMC435 placebo /Peg IFNa2A/Ribavirin 48 weeks TMC435 placebo /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin
Experimental: 001 TMC435 /Peg IFNa2A/Ribavirin TMC435 placebo 12 weeks 100 mg TMC435 / 180 µg injection Peg IFNa2A/ 1000-1200 mg Ribavirin followed by 36 weeks TMC435 placebo /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin	Drug: TMC435 /Peg IFNa2A/Ribavirin 48 weeks 100 mg TMC435 /180µg injection Peg IFNa2A/1000-1200 mg Ribavirin Drug: TMC435 /Peg IFNa2A/Ribavirin TMC435 placebo 12 weeks 100 mg TMC435 / 180 µg injection Peg IFNa2A/ 1000-1200 mg Ribavirin followed by 36 weeks TMC435 placebo /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin
Experimental: 002 TMC435 /Peg IFNa2A/Ribavirin TMC435 placebo 12 weeks 150 mg TMC435 / 180 µg injection Peg IFNa2A/ 1000-1200 mg Ribavirin followed by 36 weeks TMC435 placebo /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin	Drug: TMC435 /Peg IFNa2A/Ribavirin 48 weeks 150 mg TMC435 /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin Drug: TMC435 /Peg IFNa2A/Ribavirin TMC435 placebo 12 weeks 150 mg TMC435 / 180 µg injection Peg IFNa2A/ 1000-1200 mg Ribavirin followed by 36 weeks TMC435 placebo /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin
Experimental: 003 TMC435 /Peg IFNa2A/Ribavirin TMC435 placebo 24 weeks 100 mg TMC435 / 180 µg injection Peg IFNa2A/ 1000-1200 mg Ribavirin followed by 24 weeks TMC435 placebo /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin	Drug: TMC435 placebo /Peg IFNa2A/Ribavirin 48 weeks TMC435 placebo /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin Drug: TMC435 /Peg IFNa2A/Ribavirin TMC435 placebo 24 weeks 100 mg TMC435 / 180 µg injection Peg IFNa2A/ 1000-1200 mg Ribavirin followed by 24 weeks TMC435 placebo /180 µg injection Peg IFNa2A/1000-1200 mg Ribavirin

Detailed Description:

The study is a randomized (study drug assigned by chance), double-blind (neither physician nor patient knows the name of the assigned drug), placebo-controlled Phase IIb trial with TMC435 in patients with chronic, genotype 1, hepatitis C who have failed standard treatment with pegylated interferon (Peg-INF) and ribavirin (RBV). The study will compare the efficacy, tolerability and safety of different regimens with TMC435 combined with standard treatment (Peg-INF 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. Patients 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. Treatment arms 1 and 2 will receive TMC435 with standard treatment for 12 weeks; followed by standard treatment (plus placebo) for 36 weeks. Treatment arms 3 and 4 will receive TMC435 (100 mg or 150 mg once a day) with standard treatment for 24 weeks; followed by standard treatment (plus placebo) for 24 weeks. Treatment arms 5 and 6 will receive TMC435 (100 mg or 150 mg once a day) with standard treatment for 48 weeks. Treatment arm 7 (control arm) will receive standard treatment for 48 weeks. TMC435 (either 100 mg or 150 mg) will be given by mouth once a day for either 12, 24 or 48 weeks. Placebo will be given by mouth once a day for either 24, 36 or 48 weeks. Peg-INF will be given as an injection under the skin at a dose of 180 mcg once every week for 48 weeks. RBV (either 1000 or 1200 mg, depending on your body weight) will be given by mouth twice a day for 48 weeks.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patient must have chronic hepatitis C infection (genotype 1) with HCV RNA level >= 10000 IU/mL
Patient must have failed at least 1 prior course of Peg-IFN/RBV therapy (standard treatment)
Patient must be willing to use 2 effective methods of birth control for up to 7 months after last dose of study medication

Exclusion Criteria:

Co-infection with any other Hepatitis C virus genotype or co-infection with the human immunodeficiency virus (HIV)
Evidence of decompensated liver disease
Patient has a medical condition which is a contraindication to Peg-INF or RBV therapy
History of, or any current medical condition which could impact the safety of the patient in the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00980330

Show 81 Study Locations

Sponsors and Collaborators

Tibotec Pharmaceuticals, Ireland

Investigators

Study Director:

Tibotec Pharmaceuticals Clinical Trial

Tibotec Pharmaceutical Limited

More Information

No publications provided

Responsible Party:	Compound Development Team Leader, Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:	NCT00980330 History of Changes
Other Study ID Numbers:	CR016063, TMC435-TiDP16-C206
Study First Received:	September 10, 2009
Last Updated:	January 10, 2012
Health Authority:	United States: Food and Drug Administration; Ireland: Irish Agriculture and Food Development Authority; Canada: Health Canada; Great Britain: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Tibotec Pharmaceuticals, Ireland:

Hepatitis C
Peginterferon alpha-2a
PegIFNalpha-2a
RBV
Ribavirin

Placebo
TMC435-TIDP16-C206
TMC435-C206
TMC435
HCV

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferon-alpha
Interferon Alfa-2b
Ribavirin

Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 12, 2012