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Safety and Efficacy of SCH 503034 in Previously Untreated Subjects With Chronic Hepatitis C Infected With Genotype 1 (Study P03523)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00423670
First received: January 17, 2007
Last updated: February 16, 2015
Last verified: February 2015
Results First Received: May 13, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Chronic Hepatitis C
Interventions: Drug: boceprevir (SCH 503034)
Drug: peginterferon-alfa 2b (PegIntron)
Drug: ribavirin
Drug: ribavirin (low-dose)

  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

765 participants were screened in the study, 598 were randomized of which 3 participants were not

treated (Arm 1-7). Participants were assigned to Part I (with standard dosing for ribavirin) or Part II (to explore low-dose ribavirin). All participants that completed or discontinued treatment were scheduled to enter follow-up phase per protocol.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants in Arm 1 (Part I) who had detectable Hepatitis C Virus-ribonucleic acid (HCV-RNA) at Treatment Week (TW) 24 were offered boceprevir in addition to PegIntron and ribavirin for an additional 24 weeks of treatment, and switched to a new arm, Arm 8.

Reporting Groups
  Description
Arm 1. PEG +RBV for 48 Wks (Part I)

PegIntron (1.5 μg/kg, once weekly [QW]) plus ribavirin (800 to 1400 mg/day) for 48 weeks.

• Participants with detectable HCV-RNA levels after 24 weeks of treatment had the option of crossing over to receive 24 weeks of PegIntron, ribavirin, and boceprevir (800 mg, thrice a day [TID]) for 24 additional weeks. Total treatment duration was up to 54 weeks.

Arm 2. PEG + RBV + BOC for 28 Wks (Part I) Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead-in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
Arm 4. PEG +RBV + BOC for 48 Wks (Part I) Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
Arm 5. PEG + RBV + BOC (From Wk 4) for 44 Wks (Part I) PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead-in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
Arm 6. PEG + RBV + BOC for 48 Wks (Part II) PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 8. PEG + RBV + BOC (From Wk 24) for 48 Wks (Part I) Participants that started in Arm 1 and had detectable HCV-RNA levels after 24 weeks of treatment had the option of receiving boceprevir (800 mg TID) with PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day). Participants that took the option of crossing over to receive 24 weeks of PegIntron, ribavirin, and boceprevir (800 mg TID) for 24 additional weeks constitute Arm 8. The total treatment duration was up to 54 weeks.

Participant Flow for 2 periods

Period 1:   Treatment Period
    Arm 1. PEG +RBV for 48 Wks (Part I)   Arm 2. PEG + RBV + BOC for 28 Wks (Part I)   Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)   Arm 4. PEG +RBV + BOC for 48 Wks (Part I)   Arm 5. PEG + RBV + BOC (From Wk 4) for 44 Wks (Part I)   Arm 6. PEG + RBV + BOC for 48 Wks (Part II)   Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)   Arm 8. PEG + RBV + BOC (From Wk 24) for 48 Wks (Part I)
STARTED   104   107   103   103   103   16   59   36 [1] 
COMPLETED   52   77   76   63   76   8   28   15 
NOT COMPLETED   52   30   27   40   27   8   31   21 
Switched to Arm 8 at TW 24                36                0                0                0                0                0                0                0 
Adverse Event                8                12                15                20                9                4                7                2 
Protocol-defined clinical event                0                7                4                12                5                4                16                15 
Lost to Follow-up                2                1                3                1                6                0                3                1 
Subject withdrew (not treatment related)                3                9                4                4                5                0                3                0 
Investigator decision                0                0                0                0                0                0                0                1 
Non-compliance with protocol                3                1                1                3                2                0                2                2 
[1] Arm 8 were Arm 1 participants that were positive for HCV-RNA at TW 24 and had the option to switch.

Period 2:   Follow-up Period
    Arm 1. PEG +RBV for 48 Wks (Part I)   Arm 2. PEG + RBV + BOC for 28 Wks (Part I)   Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)   Arm 4. PEG +RBV + BOC for 48 Wks (Part I)   Arm 5. PEG + RBV + BOC (From Wk 4) for 44 Wks (Part I)   Arm 6. PEG + RBV + BOC for 48 Wks (Part II)   Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)   Arm 8. PEG + RBV + BOC (From Wk 24) for 48 Wks (Part I)
STARTED   97   100   96   96   91   14   50   35 
COMPLETED   94   84   85   91   89   14   41   32 
NOT COMPLETED   3   16   11   5   2   0   9   3 
Lost to Follow-up                0                12                8                3                1                0                5                0 
Subject withdrew (not treatment related)                1                4                2                1                1                0                1                1 
Non-compliance with protocol                2                0                1                1                0                0                3                2 



  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
Arm 1. PEG +RBV for 48 Wks (Part I)

PegIntron (1.5 μg/kg QW) plus ribavirin (800 to 1400 mg/day) for 48 weeks.

• Participants with detectable HCV-RNA levels after 24 weeks of treatment had to receive 24 weeks of PegIntron, ribavirin and boceprevir (800 mg TID) for 24 additional weeks. Total treatment duration was up to 54 weeks.

Arm 2. PEG + RBV + BOC for 28 Wks (Part I) Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
Arm 4. PEG +RBV + BOC for 48 Wks (Part I) Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
Arm 6. PEG + RBV + BOC for 48 Wks (Part II) PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Total Total of all reporting groups

Baseline Measures
   Arm 1. PEG +RBV for 48 Wks (Part I)   Arm 2. PEG + RBV + BOC for 28 Wks (Part I)   Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)   Arm 4. PEG +RBV + BOC for 48 Wks (Part I)   Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)   Arm 6. PEG + RBV + BOC for 48 Wks (Part II)   Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)   Total 
Overall Participants Analyzed 
[Units: Participants]
 104   107   103   103   103   16   59   595 
Age [1] 
[Units: Years]
Mean (Standard Deviation)
 48.3  (6.9)   46.4  (8.0)   47.7  (7.4)   46.7  (8.8)   47.6  (8.3)   50.3  (8.5)   48.7  (5.8)   47.5  (7.7) 
[1] Overall age characteristics were displayed for Arm 1 through Arm 7. Participants from Arm 1 (Part I) who had detectable HCV-RNA at TW 24, had the option to switch to a new arm, Arm 8.
Gender [1] 
[Units: Participants]
               
Female   34   44   52   40   45   7   18   240 
Male   70   63   51   63   58   9   41   355 
[1] Overall gender characteristics were displayed for Arm 1 through Arm 7. Participants from Arm 1 (Part I) who had detectable HCV-RNA TW 24, had the option to switch to a new arm, Arm 8.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Sustained Virologic Response (SVR)   [ Time Frame: From follow-up week (FW) 24 up to end of follow-up (EOF) ]

2.  Secondary:   Number of Participants With SVR Based on a 4-week lead-in Treatment With PegIntron and Ribavirin   [ Time Frame: From FW 24 up to EOF ]

3.  Secondary:   Number of Participants With SVR Based on Duration of Boceprevir Treatment   [ Time Frame: From FW 24 up to EOF ]

4.  Secondary:   Number of Participants Negative for HCV-RNA at FW 12   [ Time Frame: At FW 12 ]

5.  Secondary:   Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization   [ Time Frame: 72 weeks post randomization ]

6.  Secondary:   Number of Participants With an Early Virologic Response (EVR) That Achieved SVR   [ Time Frame: At TW 12, and at FW 24 up to EOF ]

7.  Secondary:   Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR   [ Time Frame: At FW 12 and FW 24 up to EOF ]
  Hide Outcome Measure 7

Measure Type Secondary
Measure Title Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR
Measure Description

Treatment-naïve adults with CHC genotype 1 were assigned study medication. Participants with undetectable HCV-RNA at FW 12 that achieved SVR (have undetectable HCV-RNA at FW 24 (up to EOF) are reported.

Participants missing data at FW 24 were considered to achieve SVR if

  1. he/she had undetectable HCV-RNA at FW 12 or later
  2. if he/she returned later to the study center and had undetectable HCV-RNA.

HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.

Time Frame At FW 12 and FW 24 up to EOF  
Safety Issue No  

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.
Participants with undetectable HCV-RNA at FW 12.

Reporting Groups
  Description
Arm 1. PEG +RBV for 48 Wks (Part I)

PegIntron (1.5 μg/kg QW) plus ribavirin (800 to 1400 mg/day) for 48 weeks.

• Participants with detectable HCV-RNA levels after 24 weeks of treatment had to receive 24 weeks of PegIntron, ribavirin and boceprevir (800 mg TID) for 24 additional weeks. Total treatment duration was up to 54 weeks.

Arm 2. PEG + RBV + BOC for 28 Wks (Part I) Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
Arm 4. PEG +RBV + BOC for 48 Wks (Part I) Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
Arm 6. PEG + RBV + BOC for 48 Wks (Part II) PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.

Measured Values
   Arm 1. PEG +RBV for 48 Wks (Part I)   Arm 2. PEG + RBV + BOC for 28 Wks (Part I)   Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)   Arm 4. PEG +RBV + BOC for 48 Wks (Part I)   Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)   Arm 6. PEG + RBV + BOC for 48 Wks (Part II)   Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) 
Participants Analyzed 
[Units: Participants]
 39   60   59   69   76   8   21 
Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR 
[Units: Participants]
             
HCV-RNA negative at EOF   39   58   58   69   76   8   20 
HCV-RNA positive at EOF   0   2   1   0   0   0   1 
Missing HCV-RNA at EOF   0   0   0   0   0   0   0 

No statistical analysis provided for Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR



8.  Secondary:   Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR   [ Time Frame: At FW 24 up to EOF and at 72 weeks post randomization ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
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