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 ]

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 ]

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

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

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

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


  Serious Adverse Events
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Time Frame Adverse events were collected from randomization through Week 72.
Additional Description

One participant randomized to the boceprevir arm never received study drug.

Adverse events for the 4 participants who crossed-over to boceprevir treatment at Treatment Week 24 (TW24) are included in the assigned treatment arm (PegIFN-2b + RBV ) until TW24 and are presented separately for the period following the crossover.


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.
Boceprevir Crossover (After Treatment Week 24) PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600- 1400 mg/day, orally, divided into two daily doses) plus boceprevir (800 mg, orally, 3 times per day) for up to 44 weeks with 24 weeks post-treatment follow-up.

Serious Adverse Events
    PegIFN-2b+RBV     PegIFN-2b+RBV+Boceprevir     Boceprevir Crossover  
Total, serious adverse events        
# participants affected / at risk     7/34 (20.59%)     11/64 (17.19%)     0/4 (0.00%)  
Blood and lymphatic system disorders        
ANAEMIA † 1      
# participants affected / at risk     2/34 (5.88%)     2/64 (3.13%)     0/4 (0.00%)  
# events     2     3     0  
LYMPHADENOPATHY † 1      
# participants affected / at risk     0/34 (0.00%)     1/64 (1.56%)     0/4 (0.00%)  
# events     0     1     0  
Cardiac disorders        
VENTRICULAR FIBRILLATION † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     0/4 (0.00%)  
# events     1     0     0  
Gastrointestinal disorders        
ABDOMINAL PAIN UPPER † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     0/4 (0.00%)  
# events     1     0     0  
PANCREATITIS † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     0/4 (0.00%)  
# events     1     0     0  
Hepatobiliary disorders        
CHOLELITHIASIS † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     0/4 (0.00%)  
# events     1     0     0  
Infections and infestations        
LUNG INFECTION PSEUDOMONAL † 1      
# participants affected / at risk     0/34 (0.00%)     1/64 (1.56%)     0/4 (0.00%)  
# events     0     1     0  
PELVIC INFLAMMATORY DISEASE † 1      
# participants affected / at risk     0/34 (0.00%)     1/64 (1.56%)     0/4 (0.00%)  
# events     0     1     0  
PNEUMONIA † 1      
# participants affected / at risk     0/34 (0.00%)     2/64 (3.13%)     0/4 (0.00%)  
# events     0     2     0  
POST PROCEDURAL INFECTION † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     0/4 (0.00%)  
# events     1     0     0  
SINUSITIS † 1      
# participants affected / at risk     0/34 (0.00%)     1/64 (1.56%)     0/4 (0.00%)  
# events     0     1     0  
URINARY TRACT INFECTION † 1      
# participants affected / at risk     0/34 (0.00%)     1/64 (1.56%)     0/4 (0.00%)  
# events     0     1     0  
VULVAL ABSCESS † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     0/4 (0.00%)  
# events     1     0     0  
Injury, poisoning and procedural complications        
LIGAMENT RUPTURE † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     0/4 (0.00%)  
# events     1     0     0  
MENISCUS LESION † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     0/4 (0.00%)  
# events     1     0     0  
OVERDOSE † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     0/4 (0.00%)  
# events     1     0     0  
Metabolism and nutrition disorders        
LACTIC ACIDOSIS † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     0/4 (0.00%)  
# events     1     0     0  
Musculoskeletal and connective tissue disorders        
ARTHRALGIA † 1      
# participants affected / at risk     0/34 (0.00%)     1/64 (1.56%)     0/4 (0.00%)  
# events     0     1     0  
Nervous system disorders        
SYNCOPE † 1      
# participants affected / at risk     0/34 (0.00%)     1/64 (1.56%)     0/4 (0.00%)  
# events     0     1     0  
Psychiatric disorders        
DEPRESSION † 1      
# participants affected / at risk     0/34 (0.00%)     1/64 (1.56%)     0/4 (0.00%)  
# events     0     1     0  
SUICIDE ATTEMPT † 1      
# participants affected / at risk     0/34 (0.00%)     1/64 (1.56%)     0/4 (0.00%)  
# events     0     1     0  
Renal and urinary disorders        
RENAL FAILURE † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     0/4 (0.00%)  
# events     1     0     0  
RENAL FAILURE ACUTE † 1      
# participants affected / at risk     0/34 (0.00%)     1/64 (1.56%)     0/4 (0.00%)  
# events     0     1     0  
Respiratory, thoracic and mediastinal disorders        
PULMONARY EMBOLISM † 1      
# participants affected / at risk     0/34 (0.00%)     2/64 (3.13%)     0/4 (0.00%)  
# events     0     2     0  
PULMONARY HYPERTENSION † 1      
# participants affected / at risk     0/34 (0.00%)     1/64 (1.56%)     0/4 (0.00%)  
# events     0     1     0  
RESPIRATORY FAILURE † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     0/4 (0.00%)  
# events     1     0     0  
Surgical and medical procedures        
CHOLECYSTECTOMY † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     0/4 (0.00%)  
# events     1     0     0  
Vascular disorders        
DEEP VEIN THROMBOSIS † 1      
# participants affected / at risk     0/34 (0.00%)     1/64 (1.56%)     0/4 (0.00%)  
# events     0     1     0  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 15.0




  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
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  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