A Phase 2b, Safety and Efficacy Study of Boceprevir in Patients Coinfected With HIV and Hepatitis C (P05411 AM4)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00959699
First received: July 29, 2009
Last updated: July 23, 2014
Last verified: July 2014
Results First Received: May 8, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: HIV Infections
Hepatitis C
HCV Infection
Interventions: Drug: PegIFN-2b
Drug: RBV
Drug: Placebo to Boceprevir
Drug: Boceprevir

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
One participant in the pegylated interferon alfa-2b (PegIFN-2b) + ribavirin (RBV) + boceprevir group withdrew from the study after randomization but prior to administration of any study treatment.

Reporting Groups
  Description
PegIFN-2b + RBV PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600-1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by placebo to boceprevir plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up (Control Arm). Participants who do not achieve HCV-RNA <9.3 IU/mL by Treatment Week 24 (TW24) are eligible to cross-over and receive boceprevir along with the PegIFN-2b and RBV for up to 44 weeks.
PegIFN-2b + RBV + Boceprevir PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600- 1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by boceprevir (800 mg, orally, 3 times per day) plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up.

Participant Flow for 2 periods

Period 1:   Treatment Period
    PegIFN-2b + RBV     PegIFN-2b + RBV + Boceprevir  
STARTED     34     65  
Treated     34     64  
COMPLETED     11 [1]   40  
NOT COMPLETED     23     25  
Adverse Event                 3                 13  
Lack of Efficacy                 15                 6  
Lost to Follow-up                 0                 1  
Withdrawal by Subject                 1                 3  
Non-Compliance with Protocol                 0                 1  
Did not receive treatment                 0                 1  
Futility/crossover to boceprevir                 4                 0  
[1] At TW24, 4 participants not achieving undetectable HCV-RNA crossed-over and received boceprevir.

Period 2:   Follow-up Period
    PegIFN-2b + RBV     PegIFN-2b + RBV + Boceprevir  
STARTED     33 [1]   62 [2]
COMPLETED     27     56  
NOT COMPLETED     6     6  
Lost to Follow-up                 3                 2  
Withdrawal by Subject                 3                 4  
[1] 1 participant didn't enter Follow-up; participants discontinuing treatment could enter Follow-up.
[2] 2 participants didn't enter Follow-up; participants discontinuing treatment could enter Follow-up.



  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
PegIFN-2b + RBV PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600-1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by placebo to boceprevir plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up (Control Arm). Participants who do not achieve HCV-RNA <9.3 IU/mL by Treatment Week 24 (TW24) are eligible to cross-over and receive boceprevir along with the PegIFN-2b and RBV for up to 44 weeks.
PegIFN-2b + RBV + Boceprevir PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600- 1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by boceprevir (800 mg, orally, 3 times per day) plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up.
Total Total of all reporting groups

Baseline Measures
    PegIFN-2b + RBV     PegIFN-2b + RBV + Boceprevir     Total  
Number of Participants  
[units: participants]
  34     64     98  
Age  
[units: years]
Mean ± Standard Deviation
  45.1  ± 9.8     42.9  ± 8.3     43.6  ± 8.8  
Gender  
[units: participants]
     
Female     12     18     30  
Male     22     46     68  



  Outcome Measures
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1.  Primary:   Percentage of Participants Achieving Sustained Viral Response (SVR) at Follow-up Week 24 (FW24) Among Randomized Participants Who Received At Least One Dose of Trial Medication   [ Time Frame: Up to Week 72 ]

Measure Type Primary
Measure Title Percentage of Participants Achieving Sustained Viral Response (SVR) at Follow-up Week 24 (FW24) Among Randomized Participants Who Received At Least One Dose of Trial Medication
Measure Description SVR24 is defined as undetectable plasma hepatitis C virus ribonucleic acid (HCV-RNA) at 24 weeks after the end of all study treatment. If there was no value in the FW24 visit window, the closest value available chronologically after this window was used; if a value was still missing after that, the value from Follow-up Week 12 (FW12) was used. HCV-RNA is detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL.
Time Frame Up to Week 72  
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.
All randomized participants receiving at least one dose of any study medication (Full Analysis Set); this includes 3 participants who did not enter the Follow-Up Period.

Reporting Groups
  Description
PegIFN-2b + RBV PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600-1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by placebo to boceprevir plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up (Control Arm). Participants who do not achieve HCV-RNA <9.3 IU/mL by Treatment Week 24 (TW24) are eligible to cross-over and receive boceprevir along with the PegIFN-2b and RBV for up to 44 weeks.
PegIFN-2b + RBV + Boceprevir PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600- 1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by boceprevir (800 mg, orally, 3 times per day) plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up.

Measured Values
    PegIFN-2b + RBV     PegIFN-2b + RBV + Boceprevir  
Number of Participants Analyzed  
[units: participants]
  34     64  
Percentage of Participants Achieving Sustained Viral Response (SVR) at Follow-up Week 24 (FW24) Among Randomized Participants Who Received At Least One Dose of Trial Medication  
[units: percentage of participants]
  29.4     62.5  


Statistical Analysis 1 for Percentage of Participants Achieving Sustained Viral Response (SVR) at Follow-up Week 24 (FW24) Among Randomized Participants Who Received At Least One Dose of Trial Medication
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.0008
Strata-Adjusted Difference [4] 33.7
95% Confidence Interval ( 14.1 to 53.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The methodology for 95% Confidence Interval (CI) is based on a Modified Koch approach which adjusted for Randomization Strata of Cirrhosis/Fibrosis (Yes or No). The adjustment of randomization strata of HCV-RNA (< or >= 800,000 IU/mL) was not possible due to sparse data.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The Cochran-Mantel-Haenszel p-value is adjusted for randomization strata of HCV-RNA (< or >= 800,000 IU/mL) and Cirrhosis/Fibrosis (Yes or No)
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Percentage of Participants Achieving SVR24 Among Randomized Participants Who Received At Least One Dose of Boceprevir (Experimental) or Placebo (Control)   [ Time Frame: Up to Week 72 ]

Measure Type Secondary
Measure Title Percentage of Participants Achieving SVR24 Among Randomized Participants Who Received At Least One Dose of Boceprevir (Experimental) or Placebo (Control)
Measure Description SVR24 is defined as undetectable plasma HCV-RNA 24 weeks after the end of all study treatment. If there was no value in the FW24 visit window, the closest value available chronologically after this window was used; if a value was still missing after that, the value from FW12 was used. HCV-RNA is detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL.
Time Frame Up to Week 72  
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.
All randomized participants receiving one dose of boceprevir (PegIFN-2b + RBV + Boceprevir group) or placebo to boceprevir (PegIFN-2b + RBV group), defined as the Modified Intent-to-Treat Population; this includes 2 participants who did not enter the Follow-up Period.

Reporting Groups
  Description
PegIFN-2b + RBV PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600-1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by placebo to boceprevir plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up (Control Arm). Participants who do not achieve HCV-RNA <9.3 IU/mL by Treatment Week 24 (TW24) are eligible to cross-over and receive boceprevir along with the PegIFN-2b and RBV for up to 44 weeks.
PegIFN-2b + RBV + Boceprevir PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600- 1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by boceprevir (800 mg, orally, 3 times per day) plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up.

Measured Values
    PegIFN-2b + RBV     PegIFN-2b + RBV + Boceprevir  
Number of Participants Analyzed  
[units: participants]
  33     62  
Percentage of Participants Achieving SVR24 Among Randomized Participants Who Received At Least One Dose of Boceprevir (Experimental) or Placebo (Control)  
[units: percentage of participants]
  30.3     64.5  


Statistical Analysis 1 for Percentage of Participants Achieving SVR24 Among Randomized Participants Who Received At Least One Dose of Boceprevir (Experimental) or Placebo (Control)
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.0007
Observed Difference [4] 34.2
95% Confidence Interval ( 14.5 to 53.9 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The methodology for 95% CI is based on the asymptotic normal approximation to the binomial distribution
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The Cochran-Mantel-Haenszel p-value is adjusted for randomization strata of HCV-RNA (< or >= 800,000 IU/mL) and Cirrhosis/Fibrosis (Yes or No)
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Percentage of Participants With Early Virologic Response (EVR) Who Achieved SVR24   [ Time Frame: Up to Week 12 ]

Measure Type Secondary
Measure Title Percentage of Participants With Early Virologic Response (EVR) Who Achieved SVR24
Measure Description EVR was defined as undetectable HCV-RNA at Treatment Week (TW) 2, 4, 8, or 12. HCV-RNA was detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL.
Time Frame Up to Week 12  
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.
All randomized participants receiving at least one dose of any study medication (Full Analysis Set); this includes 3 participants who did not enter the Follow-Up Period. No participants had undetectable HCV-RNA at Week 2; the “n” value in the table below represents the number of participants with EVR at that time point.

Reporting Groups
  Description
PegIFN-2b + RBV PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600-1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by placebo to boceprevir plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up (Control Arm). Participants who do not achieve HCV-RNA <9.3 IU/mL by Treatment Week 24 (TW24) are eligible to cross-over and receive boceprevir along with the PegIFN-2b and RBV for up to 44 weeks.
PegIFN-2b + RBV + Boceprevir PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600- 1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by boceprevir (800 mg, orally, 3 times per day) plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up.

Measured Values
    PegIFN-2b + RBV     PegIFN-2b + RBV + Boceprevir  
Number of Participants Analyzed  
[units: participants]
  34     64  
Percentage of Participants With Early Virologic Response (EVR) Who Achieved SVR24  
[units: percentage of participants]
   
HCV-RNA undetectable at Week 2 (n=0, 0)     0     0  
HCV-RNA undetectable at Week 4 (n=3, 3)     100     100  
HCV-RNA undetectable at Week 8 (n=5, 27)     100     92.6  
HCV-RNA undetectable at Week 12 (n=8, 38)     87.5     92.1  

No statistical analysis provided for Percentage of Participants With Early Virologic Response (EVR) Who Achieved SVR24



4.  Secondary:   Percentage of Participants With Undetectable HCV-RNA at Follow-up Week 12 (FW12)   [ Time Frame: Up to Week 60 ]

Measure Type Secondary
Measure Title Percentage of Participants With Undetectable HCV-RNA at Follow-up Week 12 (FW12)
Measure Description The virologic response at FW12 was considered SVR12 with an additional rule for handling missing data: participants with missing HCV-RNA assessment at FW12 but having non-missing, undetectable HCV-RNA assessments at both FW4 and FW24, were assumed to be responders for SVR12. HCV-RNA was detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL.
Time Frame Up to Week 60  
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.
All randomized participants receiving at least one dose of any study medication (Full Analysis Set); this includes 3 participants who did not enter the Follow-Up Period.

Reporting Groups
  Description
PegIFN-2b + RBV PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600-1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by placebo to boceprevir plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up (Control Arm). Participants who do not achieve HCV-RNA <9.3 IU/mL by Treatment Week 24 (TW24) are eligible to cross-over and receive boceprevir along with the PegIFN-2b and RBV for up to 44 weeks.
PegIFN-2b + RBV + Boceprevir PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600- 1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by boceprevir (800 mg, orally, 3 times per day) plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up.

Measured Values
    PegIFN-2b + RBV     PegIFN-2b + RBV + Boceprevir  
Number of Participants Analyzed  
[units: participants]
  34     64  
Percentage of Participants With Undetectable HCV-RNA at Follow-up Week 12 (FW12)  
[units: percentage of participants]
  26.5     62.5  

No statistical analysis provided for Percentage of Participants With Undetectable HCV-RNA at Follow-up Week 12 (FW12)



5.  Secondary:   Change From Baseline in log10 HCV-RNA at Treatment Week 4 (TW4)   [ Time Frame: Baseline and Week 4 ]

Measure Type Secondary
Measure Title Change From Baseline in log10 HCV-RNA at Treatment Week 4 (TW4)
Measure Description This is a measure of the change in the amount of HCV-RNA in the plasma at the end of 4 weeks of treatment. HCV-RNA was detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL.
Time Frame Baseline and Week 4  
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.
All randomized participants receiving at least one dose of any study medication (Full Analysis Set); this includes 3 participants who did not enter the Follow-Up Period.

Reporting Groups
  Description
PegIFN-2b + RBV PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600-1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by placebo to boceprevir plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up (Control Arm). Participants who do not achieve HCV-RNA <9.3 IU/mL by Treatment Week 24 (TW24) are eligible to cross-over and receive boceprevir along with the PegIFN-2b and RBV for up to 44 weeks.
PegIFN-2b + RBV + Boceprevir PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600- 1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by boceprevir (800 mg, orally, 3 times per day) plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up.

Measured Values
    PegIFN-2b + RBV     PegIFN-2b + RBV + Boceprevir  
Number of Participants Analyzed  
[units: participants]
  34     64  
Change From Baseline in log10 HCV-RNA at Treatment Week 4 (TW4)  
[units: participants]
   
Participants with <1 positive log drop     15     28  
Participants with >= 1 positive log drop     16     32  
Participants with undetectable HCV-RNA     3     3  
Participants with missing data     0     1  

No statistical analysis provided for Change From Baseline in log10 HCV-RNA at Treatment Week 4 (TW4)



6.  Secondary:   Percentage of Participants With HCV Virologic Breakthrough or Incomplete Virologic Response/Rebound   [ Time Frame: Up to Week 72 ]

Measure Type Secondary
Measure Title Percentage of Participants With HCV Virologic Breakthrough or Incomplete Virologic Response/Rebound
Measure Description Virologic breakthrough is defined as achieving undetectable HCV-RNA and subsequently having an HCV-RNA level of >1000 IU/mL. Incomplete Virologic Response/Rebound is defined as having a one log10 increase in HCV-RNA from the participant's nadir, with an HCV-RNA >1000 IU/mL. HCV-RNA was detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL.
Time Frame Up to Week 72  
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.
All randomized participants receiving at least one dose of any study medication (Full Analysis Set); this includes 3 participants who did not enter the Follow-Up Period.

Reporting Groups
  Description
PegIFN-2b + RBV PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600-1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by placebo to boceprevir plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up (Control Arm). Participants who do not achieve HCV-RNA <9.3 IU/mL by Treatment Week 24 (TW24) are eligible to cross-over and receive boceprevir along with the PegIFN-2b and RBV for up to 44 weeks.
PegIFN-2b + RBV + Boceprevir PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600- 1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by boceprevir (800 mg, orally, 3 times per day) plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up.

Measured Values
    PegIFN-2b + RBV     PegIFN-2b + RBV + Boceprevir  
Number of Participants Analyzed  
[units: participants]
  34     64  
Percentage of Participants With HCV Virologic Breakthrough or Incomplete Virologic Response/Rebound  
[units: percentage of participants]
   
Virologic breakthrough     0     6.3  
Incomplete response     17.6     9.4  

No statistical analysis provided for Percentage of Participants With HCV Virologic Breakthrough or Incomplete Virologic Response/Rebound




  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
No text entered.


  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: Vice President, Late Stage Development Group Leader
Organization: Merck Sharp & Dohme Corp.
e-mail: ClinicalTrialsDisclosure@merck.com


No publications provided by Merck Sharp & Dohme Corp.

Publications automatically indexed to this study:

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00959699     History of Changes
Other Study ID Numbers: P05411, MK-3034-025
Study First Received: July 29, 2009
Results First Received: May 8, 2013
Last Updated: July 23, 2014
Health Authority: United States: Food and Drug Administration