Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Study to Assess the Safety, Tolerability and Efficacy of TMC435 Along With Pegylated Interferon Alpha-2a (Pegasys) and Ribavirin (Copegus) Triple Therapy in Chronic Hepatitis C Genotype-1 Infected Patients Co-infected With Human Immunodeficiency Virus-Type 1

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen R&D Ireland
ClinicalTrials.gov Identifier:
NCT01479868
First received: October 18, 2011
Last updated: October 28, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to evaluate the safety and tolerability of TMC435 along with pegylated interferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) triple therapy in hepatitis C virus genotype-1 infected subjects, co-infected with human immunodeficiency virus-type 1, and to evaluate the number of patients with sustained virologic response (SVR) at 12 weeks after the planned end of treatment.


Condition Intervention Phase
Hepatitis C Virus Genotype-1
Drug: TMC435
Drug: Pegylated interferon alpha-2a
Drug: Ribavirin
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of TMC435 Plus PegIFNα-2a (Pegasys) and Ribavirin (Copegus) Triple Therapy in Chronic Hepatitis C Genotype-1 Infected Subjects Who Are Co-infected With Human Immunodeficiency Virus Type 1 (HIV-1)

Resource links provided by NLM:


Further study details as provided by Janssen R&D Ireland:

Primary Outcome Measures:
  • Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12) [ Time Frame: 12 weeks after end of treatment (Week 24 or 48) ] [ Designated as safety issue: No ]
    The SVR 12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 25 international unit per milliliter (IU/mL) undetectable at the actual end of treatment (EOT), and HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable at 12 Weeks after end of treatment.


Secondary Outcome Measures:
  • Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24) [ Time Frame: 24 weeks after end of treatment (Week 24 or 48) ] [ Designated as safety issue: No ]
    The SVR 24 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 25 international unit per milliliter (IU/mL) undetectable at the actual end of treatment (EOT), and HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable at 24 weeks after end of treatment.

  • Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable [ Time Frame: Week 4, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Percentage of participants with HCV RNA less than (<) 25 IU/mL undetectable (undet.) or detectable (det.)/undetectable at specific time points were observed.

  • Percentage of Participants With On-treatment Failure [ Time Frame: Week 1 to 48 ] [ Designated as safety issue: No ]
    Participants were considered as an on-treatment failure if, at actual end of treatment (EOT), there was confirmed detectable HCV RNA levels.

  • Percentage of Participants With Viral Breakthrough [ Time Frame: Week 1 to 48 ] [ Designated as safety issue: No ]
    Confirmed increase of more than 1 log10 IU per mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of more than 100 IU per mL in participants whose HCV RNA levels had previously been below the limit of quantification (less than 25 IU per mL detectable) or undetectable (less than 25 IU per mL undetectable), while on study therapy.

  • Percentage of Participants With Viral Relapse [ Time Frame: Week 1 to 72 ] [ Designated as safety issue: No ]
    Participants were considered to have a viral relapse when, at actual end of treatment, HCV RNA levels were less than 25 IU per mL undetectable; and during the follow-up period, HCV RNA levels were more than or equal to 25 IU per mL.

  • Percentage of Participants With Normalized Alanine Aminotransferase Levels [ Time Frame: Baseline up to Week 72 ] [ Designated as safety issue: No ]
    Participants with normalized alanine aminotransferase levels observed whose alanine aminotransferase levels were out of range at Baseline.

  • Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure [ Time Frame: Baseline to Week 72. ] [ Designated as safety issue: No ]
    Participants had confirmed HIV virologic failure if HIV viral load values were greater than or equal to 50 or 200 copies/mL among those who previously had less than 50 copies/mL.

  • Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load [ Time Frame: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4+ Cell Count [ Time Frame: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72 ] [ Designated as safety issue: No ]
  • Change From Baseline in CD4+ Cell Count in Percentage [ Time Frame: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72 ] [ Designated as safety issue: No ]
  • Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: Week 1 to Week 72 ] [ Designated as safety issue: Yes ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to Day 126 that were absent before treatment or that worsened relative to pre-treatment state.


Enrollment: 109
Study Start Date: October 2011
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TMC435 + pegylated interferon alpha-2a + ribavirin
Patients will be administered TMC435 150 mg along with pegylated interferon alpha-2a 180 microgram and ribavirin 1000 or 1200 mg for 12 weeks. Pegylated interferon alpha-2a and ribavirin will only be continued until 24 to 48 weeks.
Drug: TMC435
TMC435 150 mg will be administered once daily for 12 weeks along with peginterferon alpha-2a and ribavirin.
Drug: Pegylated interferon alpha-2a
Pegylated interferon alpha-2a 180 microgram will be administered as subcutaneous injection of 0.5 mL until 24 to 48 weeks.
Drug: Ribavirin
Ribavirin 1000 or 1200 mg twice daily will be administered each day until 24 to 48 weeks.

Detailed Description:

This is an open-label (all the people know the identity of the intervention), single arm (study will be conducted in a single group) clinical study, to evaluate the safety, tolerability and efficacy of TMC435 along with pegylated interferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) triple therapy in adult chronic hepatitis C (CHC) genotype-1 infected patients who are co-infected with human immunodeficiency virus-type 1 (HIV-1). The study consists of 3 phases, screening phase (Week -6), treatment phase, and a follow-up phase (up to 24 weeks). In the treatment phase, patients will be classified based on their experience with previous hepatitis C virus (HCV) treatment as follows: 1) HCV treatment-naive (patients who never received medication for the treatment of HCV); 2) prior HCV relapsers (patients who received at least 24 weeks of a PegIFNα-2a and RBV-based therapy and relapsed within 1 year after the last medication intake); and 3) prior HCV non-responders (can be further classified as, null responders: patients having at least 1 prior documented course of PegIFNα-2a and RBV therapy for at least 12 consecutive weeks; or partial responders: patients having at least 20 consecutive weeks which has not been discontinued due to intolerability to PegIFNα-2a and RBV therapy). All patients will receive TMC435 once daily along with PegIFNα-2a and RBV for 12 weeks. Patients who are continuing treatment only with PegIFNα-2a and RBV will follow until 24 or 48 weeks. Pharmacokinetics will be measured after collection of blood samples. Safety evaluations for adverse events, clinical laboratory tests, electrocardiogram, vital signs, physical examinations, and specific toxicities will be performed throughout the study. The total duration of treatment is approximately of 24 weeks.

  Eligibility

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

Inclusion Criteria:

  • A liver biopsy required within 3 years prior to screening unless the patient has a contraindication for a liver biopsy
  • Patients with bridging fibrosis or cirrhosis and without a liver biopsy result within 2 years prior screening must have an ultrasound taken within 2 months prior to the screening visit or during screening with no findings suspicious for hepatocellular carcinoma (HCC)
  • Genotype-1 hepatitis C virus (HCV) infection
  • Plasma HCV ribonucleic acid (RNA) of more than 10,000 IU per mL
  • Documented human immunodeficiency virus-type 1 (HIV-1) infection at least 6 months prior to screening

Exclusion Criteria:

  • Patient showing evidence of hepatic decompensation (ie, history or current evidence of ascites, bleeding varices or hepatic encephalopathy, albumin serum concentration less than 3.3 gm per dL, prolonged prothrombin time [PT] expressed as international normalized ratio [INR] more than 1.5)
  • Any liver disease of non-HCV etiology
  • Co-infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive)
  • An acute HIV-1 infection; or HIV-2 infection
  • Change in antiretroviral (ARV) regimen within the last 4 weeks prior screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01479868

  Hide Study Locations
Locations
United States, California
Los Angeles, California, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Florida
Orlando, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
United States, Illinois
Chicago, Illinois, United States
United States, New Jersey
Newark, New Jersey, United States
United States, New York
Albany, New York, United States
New York, New York, United States
United States, Texas
Dallas, Texas, United States
Houston, Texas, United States
Canada, Ontario
Toronto, Ontario, Canada
Canada, Quebec
Montreal, Quebec, Canada
France
Lyon, France
Montpellier Cedex 5, France
Nantes, France
Paris, France
Germany
Berlin, Germany
Bonn, Germany
Düsseldorf, Germany
Frankfurt, Germany
Freiburg, Germany
Hamburg, Germany
Köln, Germany
Portugal
Amadora, Portugal
Lisboa, Portugal
Porto, Portugal
Puerto Rico
San Juan, Puerto Rico
Spain
Badalona, Spain
Elche, Spain
Madrid, Spain
United Kingdom
Brighton, United Kingdom
London, United Kingdom
Sponsors and Collaborators
Janssen R&D Ireland
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen R&D Ireland
ClinicalTrials.gov Identifier: NCT01479868     History of Changes
Obsolete Identifiers: NCT01727323
Other Study ID Numbers: CR018334, TMC435-TiDP16-C212
Study First Received: October 18, 2011
Results First Received: August 26, 2014
Last Updated: October 28, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Germany: Ethics Commission

Keywords provided by Janssen R&D Ireland:
Hepatitis C virus genotype-1
Human immunodeficiency virus-type 1
HCV-1
HIV-1
TMC435
Pegylated interferon alpha-2a
PegIFNα-2a
Pegasys
Ribavirin
RBV
Copegus

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Immunologic Deficiency Syndromes
Virus Diseases
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Immune System Diseases
Lentivirus Infections
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Interferon-alpha
Interferons
Peginterferon alfa-2a
Ribavirin
Anti-Infective Agents
Antimetabolites
Antineoplastic Agents
Antiviral Agents

ClinicalTrials.gov processed this record on November 20, 2014