TMC435HPC3001 - An Efficacy, Safety and Tolerability Study for TMC435 vs Telaprevir in Combination With PegINFα-2a and Ribavirin in Chronic Hepatitis C Patients Who Were Null or Partial Responders to Prior PegINFα-2a and Ribavirin Therapy (ATTAIN)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen R&D Ireland
ClinicalTrials.gov Identifier:
NCT01485991
First received: November 25, 2011
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to demonstrate the efficacy of TMC435 in combination with peginterferon (PegIFN) + ribavirin (RBV) by means of establishing its non- inferiority compared to an approved regimen of telaprevir + PegIFN + RBV in patients who have previously failed PegIFN.


Condition Intervention Phase
Hepatitis C
Drug: TMC435
Drug: TVR
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Phase III in Partial and Null Responders

Resource links provided by NLM:


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

Primary Outcome Measures:
  • The proportion of patients with sustained virological response 12 weeks after the planned end of treatment (SVR12) [ Time Frame: At Week 60 ] [ Designated as safety issue: Yes ]

    Patients are considered to have reached SVR12 if both conditions below are met:

    1. at the actual end of treatment: HCV RNA levels < 25 IU/mL undetectable AND
    2. at the timepoint of SVR12 (i.e., 12 weeks after the planned end of treatment): HCV RNA levels < 25 IU/mL undetectable or HCV RNA levels < 25 IU/mL detectable


Secondary Outcome Measures:
  • The proportion of patients with sustained virological response 24 weeks after the planned end of treatment (SVR24) [ Time Frame: At Week 72 ] [ Designated as safety issue: Yes ]

    Patients are considered to have reached SVR24 if both conditions below are met:

    1. at the actual end of treatment: HCV RNA levels < 25 IU/mL undetectable AND
    2. at the timepoint of SVR24 (i.e., 24 weeks after the planned end of treatment): HCV RNA levels < 25 IU/mL undetectable or HCV RNA levels < 25 IU/mL detectable


Enrollment: 766
Study Start Date: February 2012
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TMC435/PR Drug: TMC435
TMC435 Type=exact number, unit=mg, number=150, form=capsule, route=oral use. TVR placebo Form=tablet, route=oral use. TMC435 capsule is taken once daily in addition to 2 TVR placebo tablets 3 times a day for 12 weeks, and peginterferon alfa-2a and ribavirin for 48 weeks.
Active Comparator: TVR/PR Drug: TVR
TVR Type=exact number, unit=mg, number=375, form=tablet, route=oral use. TMC435 placebo Form=capsule, route=oral use. 2 TVR tablets are taken 3 times a day together with 150 mg TMC435 placebo capsule once daily for 12 weeks, in addition to peginterferon alfa-2a and ribavirin for 48 weeks

Detailed Description:

This study is a randomized (study drug assigned by chance like flipping a coin), double-blind (neither physician nor patient knows the name of the assigned drug), double-dummy (patients receive both active and inactive pills also called placebo), 2-arm, multicenter Phase III clinical study in adult treatment experienced Chronic Hepatitis C (CHC) genotype-1 infected patients who failed to respond during at least 1 previous course of PegINFα-2a/ RBV therapy. The purpose of the trial is to study the efficacy of TMC435 in combination with PegINFα-2a and RBV for 48 weeks of treatment compared to the approved regimen of telaprevir in combination with PegINFα-2a and RBV for 48 weeks of treatment. The study will consist of a screening period (maximum 6 weeks), treatment period (48 weeks) and post-treatment period (until 72 weeks after the start of treatment). For the first 12 weeks one group of patients will take TMC435 and TVR placebo, plus PegINFα-2a and RBV. The other group will take TMC435 placebo and TVR, plus PegINFα-2a and RBV. After 12 weeks, patients in both arms will only take PegINFα-2a and RBV up to week 48. After patients stop taking study medication, they will continue to go to the doctor's office for study visits until a total of 72 weeks after they start study treatment. Patients will be monitored for safety throughout the study. Study assessments at each study visit may include, but are not limited to: blood and urine collection for testing, electrocardiogram (ECG) assessments (a measurement of the electrical activity of your heart), patient questionnaires, and physical examinations.

  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 had a liver biopsy before screening (or between the screening and baseline visit), unless patient cannot undergo such a procedure or has evidence of portal hypertension not associated with cirrhosis. For patients who had a liver biopsy performed more than 2 years prior to screening or without a biopsy (because of a contraindication or portal hypertension), a non-invasive staging assessment needs to be available. Non-invasive staging assessments include FibroScan, MR-Elastography, or FibroTest/FibroSure and must not be older than 6 months prior to screening
  • Chronicity of hepatitis C virus (HCV) infection, as confirmed by one or both of the following: presence of anti-HCV antibody and/or HCV ribonucleic acid (RNA) at least 6 months prior to the screening visit and/or presence of fibrosis on biopsy
  • Genotype 1 HCV infection with plasma HCV RNA of >10,000 IU/mL (both confirmed at screening)
  • Patient must have had at least 1 documented previous course of treatment with PegINFα-2a or PegINFα-2b in combination with ribavirin (RBV) (at least 12 weeks for null responder and 20 weeks for partial responder)

Exclusion Criteria:

  • Hepatic decompensation (impaired functioning of the liver), as indicated by significant laboratory abnormalities or other active diseases
  • Infection with Human Immunodeficiency Virus (HIV) or non genotype 1 hepatitis C
  • Liver disease not related to hepatitis C infection
  • Previous chronic hepatitis C treatment, other than PegIFN and RBV
  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: NCT01485991

  Show 142 Study Locations
Sponsors and Collaborators
Janssen R&D Ireland
Investigators
Study Director: Tibotec Pharmaceuticals Limited Clinical Trial Tibotec Pharmaceutical Limited
  More Information

No publications provided

Responsible Party: Janssen R&D Ireland
ClinicalTrials.gov Identifier: NCT01485991     History of Changes
Other Study ID Numbers: CR100677, TMC435HPC3001
Study First Received: November 25, 2011
Last Updated: May 12, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Great Britain: Medicines and Healthcare Products Regulatory Agency
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Czech Republic: State Institute for Drug Control

Keywords provided by Janssen R&D Ireland:
Hepatitis C
TMC435HPC3001
TMC435
Hepatitis C Virus (HCV)
HEP C
Genotype 1
Treatment experienced
Null responders
Partial responders

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014