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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

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ClinicalTrials.gov Identifier: NCT01479868
Recruitment Status : Completed
First Posted : November 28, 2011
Results First Posted : October 29, 2014
Last Update Posted : October 29, 2014
Sponsor:
Information provided by (Responsible Party):
Janssen R&D Ireland

Study Description
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Brief Summary:
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 or disease Intervention/treatment Phase
Hepatitis C Virus Genotype-1 Drug: TMC435 Drug: Pegylated interferon alpha-2a Drug: Ribavirin Phase 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 109 participants
Intervention Model: Single Group Assignment
Masking: None (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)
Study Start Date : October 2011
Actual Primary Completion Date : August 2013
Actual Study Completion Date : August 2013

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U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
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.


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12) [ Time Frame: 12 weeks after end of treatment (Week 24 or 48) ]
    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 :
  1. Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24) [ Time Frame: 24 weeks after end of treatment (Week 24 or 48) ]
    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.

  2. 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 ]
    Percentage of participants with HCV RNA less than (<) 25 IU/mL undetectable (undet.) or detectable (det.)/undetectable at specific time points were observed.

  3. Percentage of Participants With On-treatment Failure [ Time Frame: Week 1 to 48 ]
    Participants were considered as an on-treatment failure if, at actual end of treatment (EOT), there was confirmed detectable HCV RNA levels.

  4. Percentage of Participants With Viral Breakthrough [ Time Frame: Week 1 to 48 ]
    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.

  5. Percentage of Participants With Viral Relapse [ Time Frame: Week 1 to 72 ]
    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.

  6. Percentage of Participants With Normalized Alanine Aminotransferase Levels [ Time Frame: Baseline up to Week 72 ]
    Participants with normalized alanine aminotransferase levels observed whose alanine aminotransferase levels were out of range at Baseline.

  7. Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure [ Time Frame: Baseline to Week 72. ]
    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.

  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: Week 1 to Week 72 ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01479868


  Show 32 Study Locations
Sponsors and Collaborators
Janssen R&D Ireland
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Janssen R&D Ireland
ClinicalTrials.gov Identifier: NCT01479868     History of Changes
Obsolete Identifiers: NCT01727323
Other Study ID Numbers: CR018334
TMC435-TiDP16-C212 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: November 28, 2011    Key Record Dates
Results First Posted: October 29, 2014
Last Update Posted: October 29, 2014
Last Verified: October 2014

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