A Study to Assess the Effectiveness, Safety, and Pharmacokinetics of TMC435 in Combination With Peginterferon Alfa-2a and Ribavirin in Hepatitis-C Infected Patients (DRAGON)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:
NCT00996476
First received: October 15, 2009
Last updated: March 21, 2014
Last verified: March 2014
Results First Received: October 17, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Hepatitis C, Chronic
Interventions: Drug: TMC435
Drug: PegIFNα-2a
Drug: RBV

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted between 6 July 2009 and 1 April 2011 and recruited participants with chronic Hepatitis C Virus (HCV) infection from 25 study centers in Japan. A total of 93 participants were randomized, 92 treated, and 85 completed the study (1 participant in the TMC12/PR24 100 mg arm withdrew consent and did not receive study treatment).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Treatment-naïve HCV-infected participants were randomized to 1 of 5 treatment arms and received 12 weeks of TMC435 50 or 100 mg once daily with PegIFNα-2a and ribavirin (PR) followed by 12 weeks of PR (Arm 1 and 2); 24 weeks of TMC435 50 or 100 mg once daily with PR (Arms 3 and 4); and, PR for 48 weeks (Arm 5).

Reporting Groups
  Description
TMC12/PR24 50 mg Participants received TMC435 50 mg once daily with PegIFNa-2a and ribavirin (PR) for 12 weeks followed by PR until Week 24 Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels <1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435 and PR) at Week 24. All other participants continued PR until Week 48.
TMC12/PR24 100 mg Participants received TMC435 100 mg once daily plus PegIFNa-2a and ribavirin (PR) for 12 weeks followed by PR until Week 24. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels <1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435 and PR) at Week 24. All other participants continued PR until Week 48.
TMC24/PR24 50 mg Participants received TMC435 50 mg once daily plus PegIFNa-2a and ribavirin (PR) for 24 weeks. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels <1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435, PR) at Week 24. All other participants continued PR until Week 48.
TMC24/PR24 100 mg Participants received TMC435 100 mg once daily plus PegIFNa-2a and ribavirin (PR) for 24 weeks. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels <1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435 and PR) at Week 24. All other participants continued PR until Week 48.
PR48 Control Participants received PegIFNa-2a and ribavirin (PR) for 48 weeks (PR48 control group)

Participant Flow:   Overall Study
    TMC12/PR24 50 mg     TMC12/PR24 100 mg     TMC24/PR24 50 mg     TMC24/PR24 100 mg     PR48 Control  
STARTED     27     26     13     13     13  
COMPLETED     26     23     12     13     11  
NOT COMPLETED     1     3     1     0     2  
Withdrawal by Subject                 1                 2                 1                 0                 1  
Adverse Event                 0                 1                 0                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
TMC12/PR24 50 mg Participants received TMC435 50 mg once daily with PegIFNa-2a and ribavirin (PR) for 12 weeks followed by PR until Week 24 Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels <1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435 and PR) at Week 24. All other participants continued PR until Week 48.
TMC12/PR24 100 mg Participants received TMC435 100 mg once daily plus PegIFNa-2a and ribavirin (PR) for 12 weeks followed by PR until Week 24. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels <1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435 and PR) at Week 24. All other participants continued PR until Week 48.
TMC24/PR24 50 mg Participants received TMC435 50 mg once daily plus PegIFNa-2a and ribavirin (PR) for 24 weeks. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels <1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435, PR) at Week 24. All other participants continued PR until Week 48.
TMC24/PR24 100 mg Participants received TMC435 100 mg once daily plus PegIFNa-2a and ribavirin (PR) for 24 weeks. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels <1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435 and PR) at Week 24. All other participants continued PR until Week 48.
PR48 Control Participants received PegIFNa-2a and ribavirin (PR) for 48 weeks (PR48 control group)
Total Total of all reporting groups

Baseline Measures
    TMC12/PR24 50 mg     TMC12/PR24 100 mg     TMC24/PR24 50 mg     TMC24/PR24 100 mg     PR48 Control     Total  
Number of Participants  
[units: participants]
  27     26     13     13     13     92  
Age  
[units: years]
Median ( Full Range )
  53  
  ( 31 to 67 )  
  56  
  ( 22 to 69 )  
  48  
  ( 34 to 67 )  
  54  
  ( 28 to 68 )  
  54  
  ( 20 to 66 )  
  54  
  ( 20 to 69 )  
Gender  
[units: participants]
           
Female     15     16     7     5     6     49  
Male     12     10     6     8     7     43  



  Outcome Measures
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1.  Primary:   Change in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels From Baseline to Week 4   [ Time Frame: Day 1 (Baseline) and Week 4 ]

2.  Primary:   The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During the Study   [ Time Frame: Weeks 4, 12, 24 or 48, and EOT (up to Week 24 or 48) ]

3.  Primary:   The Percentage of Participants With a Decrease of Greater Than or Equal to 2 log10 IU/mL From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Through the Post-treatment Follow-up Period   [ Time Frame: Days 1 (4 hr), 1 (8 hr), 3, Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24,28, 36, 42, 48, 52, 60, 72, and EOT (up to Week 24 or 48) ]

4.  Primary:   The Percentage of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Undetectable or Below the Limit of Quantification (<1.2 log10 IU/mL Detectable) During Treatment and During Post Treatment Follow-up   [ Time Frame: Week 4, 12, 24, 36, 48, EOT (up to Week 24 or 48), and Week 60 and 72 ]

5.  Primary:   The Number of Participants With Viral Breakthrough   [ Time Frame: Up to EOT (up to Week 24 or 48) ]

6.  Primary:   The Percentage of Participants With Viral Relapse   [ Time Frame: Week 36 or 60 ]

7.  Primary:   Actual Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values up to Week 24 in the Post-treatment Follow-up Period   [ Time Frame: Baseline, Week 4, 12, 24, 48, EOT (up to Week 24 or 48), and Weeks 60 and 72 ]

8.  Primary:   The Number of Participants With Alanine Aminotransaminase (ALT) Values Within the Normal Range at the End-of-treatment (EOT)   [ Time Frame: Day 1, Weeks 24, 48, and EOT (up to Weeks 24 or 48) ]

9.  Primary:   The Percentage of Participants With Sustained Virologic Response (SVR)   [ Time Frame: SVR4 (up to Week 28 or Week 52), SVR12 (up to Weeks 36 or 60), and SVR24 (up to Weeks 48 or 72) ]

10.  Primary:   Predose Plasma Concentrations (C0h) of TMC435 (Sparse Blood Sampling)   [ Time Frame: Weeks 4, 12, and 24 ]

11.  Primary:   Predose Plasma Concentrations (C0h) of TMC435 (Intensive Blood Sampling)   [ Time Frame: Weeks 4 to 6 ]

12.  Primary:   The Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24) for TMC435   [ Time Frame: within 15 minutes and at 1, 2, 4, 6, 8, 12, and 24 hours post-dose between Week 4 and Week 6 after the initiation of treatment ]

13.  Primary:   Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435   [ Time Frame: within 15 minutes and at 1, 2, 4, 6, 8, 12, and 24 hours post-dose between Week 4 and Week 6 after the initiation of treatment ]

14.  Primary:   The Number of Participants Who Met Virologic Stopping/Continuation Rules and Completed All Study Medications   [ Time Frame: Week 24 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated. "Primary" was chosen for each outcome measure because "Exploratory" is not available as an outcome measure type.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: DIrector
Organization: Janssen Pharmaceutical K.K., Japan
phone: 81 3 44115639


No publications provided by Janssen Pharmaceutical K.K.

Publications automatically indexed to this study:

Responsible Party: Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier: NCT00996476     History of Changes
Other Study ID Numbers: CR016402, TMC435-TiDP16-C215
Study First Received: October 15, 2009
Results First Received: October 17, 2013
Last Updated: March 21, 2014
Health Authority: Japan: Japan Pharmaceuticals And Medical Devices Evaluation Center
Japan: Pharmaceuticals and Medical Devices Agency