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: September 26, 2014
Last verified: September 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


  Other 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.


Frequency Threshold
Threshold above which other adverse events are reported   5%  

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.

Other Adverse Events
    PegIFN-2b+RBV     PegIFN-2b+RBV+Boceprevir     Boceprevir Crossover  
Total, other (not including serious) adverse events        
# participants affected / at risk     33/34     62/64     4/4  
Blood and lymphatic system disorders        
ANAEMIA † 1      
# participants affected / at risk     8/34 (23.53%)     26/64 (40.63%)     2/4 (50.00%)  
# events     8     40     2  
NEUTROPENIA † 1      
# participants affected / at risk     2/34 (5.88%)     12/64 (18.75%)     1/4 (25.00%)  
# events     2     14     1  
THROMBOCYTOPENIA † 1      
# participants affected / at risk     0/34 (0.00%)     5/64 (7.81%)     1/4 (25.00%)  
# events     0     5     1  
Cardiac disorders        
PALPITATIONS † 1      
# participants affected / at risk     0/34 (0.00%)     2/64 (3.13%)     1/4 (25.00%)  
# events     0     2     1  
Congenital, familial and genetic disorders        
PORPHYRIA † 1      
# participants affected / at risk     0/34 (0.00%)     0/64 (0.00%)     1/4 (25.00%)  
# events     0     0     1  
Eye disorders        
DRY EYE † 1      
# participants affected / at risk     2/34 (5.88%)     2/64 (3.13%)     0/4 (0.00%)  
# events     2     3     0  
Gastrointestinal disorders        
ABDOMINAL DISCOMFORT † 1      
# participants affected / at risk     0/34 (0.00%)     2/64 (3.13%)     1/4 (25.00%)  
# events     0     2     1  
ABDOMINAL PAIN † 1      
# participants affected / at risk     3/34 (8.82%)     3/64 (4.69%)     0/4 (0.00%)  
# events     3     3     0  
ABDOMINAL PAIN UPPER † 1      
# participants affected / at risk     1/34 (2.94%)     6/64 (9.38%)     0/4 (0.00%)  
# events     1     7     0  
APHTHOUS STOMATITIS † 1      
# participants affected / at risk     0/34 (0.00%)     6/64 (9.38%)     0/4 (0.00%)  
# events     0     6     0  
CHEILITIS † 1      
# participants affected / at risk     2/34 (5.88%)     5/64 (7.81%)     1/4 (25.00%)  
# events     2     6     1  
CONSTIPATION † 1      
# participants affected / at risk     5/34 (14.71%)     4/64 (6.25%)     1/4 (25.00%)  
# events     5     4     1  
DIARRHOEA † 1      
# participants affected / at risk     6/34 (17.65%)     21/64 (32.81%)     0/4 (0.00%)  
# events     8     30     0  
DRY MOUTH † 1      
# participants affected / at risk     0/34 (0.00%)     5/64 (7.81%)     0/4 (0.00%)  
# events     0     5     0  
NAUSEA † 1      
# participants affected / at risk     11/34 (32.35%)     26/64 (40.63%)     1/4 (25.00%)  
# events     12     37     1  
ORAL PAIN † 1      
# participants affected / at risk     0/34 (0.00%)     4/64 (6.25%)     0/4 (0.00%)  
# events     0     4     0  
RECTAL HAEMORRHAGE † 1      
# participants affected / at risk     0/34 (0.00%)     0/64 (0.00%)     1/4 (25.00%)  
# events     0     0     1  
TONGUE DISCOLOURATION † 1      
# participants affected / at risk     2/34 (5.88%)     0/64 (0.00%)     0/4 (0.00%)  
# events     2     0     0  
VOMITING † 1      
# participants affected / at risk     5/34 (14.71%)     18/64 (28.13%)     0/4 (0.00%)  
# events     9     23     0  
General disorders        
ASTHENIA † 1      
# participants affected / at risk     9/34 (26.47%)     22/64 (34.38%)     2/4 (50.00%)  
# events     9     30     2  
CHILLS † 1      
# participants affected / at risk     5/34 (14.71%)     5/64 (7.81%)     0/4 (0.00%)  
# events     5     5     0  
FATIGUE † 1      
# participants affected / at risk     12/34 (35.29%)     25/64 (39.06%)     0/4 (0.00%)  
# events     15     35     0  
INFLUENZA LIKE ILLNESS † 1      
# participants affected / at risk     13/34 (38.24%)     16/64 (25.00%)     0/4 (0.00%)  
# events     29     24     0  
INJECTION SITE ERYTHEMA † 1      
# participants affected / at risk     1/34 (2.94%)     4/64 (6.25%)     0/4 (0.00%)  
# events     1     4     0  
IRRITABILITY † 1      
# participants affected / at risk     5/34 (14.71%)     10/64 (15.63%)     1/4 (25.00%)  
# events     5     11     1  
MALAISE † 1      
# participants affected / at risk     2/34 (5.88%)     3/64 (4.69%)     0/4 (0.00%)  
# events     2     3     0  
OEDEMA PERIPHERAL † 1      
# participants affected / at risk     2/34 (5.88%)     3/64 (4.69%)     0/4 (0.00%)  
# events     2     3     0  
PAIN † 1      
# participants affected / at risk     1/34 (2.94%)     5/64 (7.81%)     0/4 (0.00%)  
# events     1     5     0  
PYREXIA † 1      
# participants affected / at risk     7/34 (20.59%)     24/64 (37.50%)     1/4 (25.00%)  
# events     13     60     1  
Infections and infestations        
FOLLICULITIS † 1      
# participants affected / at risk     2/34 (5.88%)     0/64 (0.00%)     0/4 (0.00%)  
# events     2     0     0  
GINGIVAL ABSCESS † 1      
# participants affected / at risk     0/34 (0.00%)     0/64 (0.00%)     1/4 (25.00%)  
# events     0     0     1  
INFLUENZA † 1      
# participants affected / at risk     4/34 (11.76%)     6/64 (9.38%)     0/4 (0.00%)  
# events     5     7     0  
NASOPHARYNGITIS † 1      
# participants affected / at risk     4/34 (11.76%)     5/64 (7.81%)     0/4 (0.00%)  
# events     4     5     0  
ORAL CANDIDIASIS † 1      
# participants affected / at risk     2/34 (5.88%)     3/64 (4.69%)     0/4 (0.00%)  
# events     2     5     0  
RESPIRATORY TRACT INFECTION † 1      
# participants affected / at risk     1/34 (2.94%)     2/64 (3.13%)     1/4 (25.00%)  
# events     1     3     1  
SINUSITIS † 1      
# participants affected / at risk     0/34 (0.00%)     5/64 (7.81%)     1/4 (25.00%)  
# events     0     6     1  
UPPER RESPIRATORY TRACT INFECTION † 1      
# participants affected / at risk     2/34 (5.88%)     1/64 (1.56%)     0/4 (0.00%)  
# events     2     1     0  
URINARY TRACT INFECTION † 1      
# participants affected / at risk     2/34 (5.88%)     3/64 (4.69%)     0/4 (0.00%)  
# events     2     3     0  
Investigations        
GAMMA-GLUTAMYLTRANSFERASE INCREASED † 1      
# participants affected / at risk     2/34 (5.88%)     0/64 (0.00%)     0/4 (0.00%)  
# events     2     0     0  
TRANSAMINASES INCREASED † 1      
# participants affected / at risk     2/34 (5.88%)     0/64 (0.00%)     0/4 (0.00%)  
# events     2     0     0  
WEIGHT DECREASED † 1      
# participants affected / at risk     1/34 (2.94%)     8/64 (12.50%)     0/4 (0.00%)  
# events     1     9     0  
Metabolism and nutrition disorders        
DECREASED APPETITE † 1      
# participants affected / at risk     6/34 (17.65%)     22/64 (34.38%)     0/4 (0.00%)  
# events     6     22     0  
HYPERTRIGLYCERIDAEMIA † 1      
# participants affected / at risk     2/34 (5.88%)     2/64 (3.13%)     1/4 (25.00%)  
# events     2     3     1  
Musculoskeletal and connective tissue disorders        
ARTHRALGIA † 1      
# participants affected / at risk     2/34 (5.88%)     7/64 (10.94%)     0/4 (0.00%)  
# events     2     7     0  
MYALGIA † 1      
# participants affected / at risk     6/34 (17.65%)     9/64 (14.06%)     0/4 (0.00%)  
# events     7     12     0  
NECK PAIN † 1      
# participants affected / at risk     2/34 (5.88%)     2/64 (3.13%)     0/4 (0.00%)  
# events     2     2     0  
PAIN IN EXTREMITY † 1      
# participants affected / at risk     2/34 (5.88%)     3/64 (4.69%)     0/4 (0.00%)  
# events     2     3     0  
Nervous system disorders        
DIZZINESS † 1      
# participants affected / at risk     2/34 (5.88%)     8/64 (12.50%)     1/4 (25.00%)  
# events     2     9     1  
DYSGEUSIA † 1      
# participants affected / at risk     5/34 (14.71%)     18/64 (28.13%)     2/4 (50.00%)  
# events     5     18     2  
HEADACHE † 1      
# participants affected / at risk     6/34 (17.65%)     18/64 (28.13%)     0/4 (0.00%)  
# events     6     63     0  
PARAESTHESIA † 1      
# participants affected / at risk     2/34 (5.88%)     2/64 (3.13%)     0/4 (0.00%)  
# events     2     2     0  
SOMNOLENCE † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     1/4 (25.00%)  
# events     1     0     1  
Pregnancy, puerperium and perinatal conditions        
PREGNANCY † 1      
# participants affected / at risk     0/34 (0.00%)     0/64 (0.00%)     1/4 (25.00%)  
# events     0     0     1  
Psychiatric disorders        
AFFECT LABILITY † 1      
# participants affected / at risk     2/34 (5.88%)     1/64 (1.56%)     1/4 (25.00%)  
# events     2     1     1  
ANXIETY † 1      
# participants affected / at risk     5/34 (14.71%)     10/64 (15.63%)     0/4 (0.00%)  
# events     8     11     0  
APATHY † 1      
# participants affected / at risk     1/34 (2.94%)     0/64 (0.00%)     1/4 (25.00%)  
# events     1     0     1  
DEPRESSED MOOD † 1      
# participants affected / at risk     1/34 (2.94%)     1/64 (1.56%)     1/4 (25.00%)  
# events     2     1     1  
DEPRESSION † 1      
# participants affected / at risk     4/34 (11.76%)     11/64 (17.19%)     0/4 (0.00%)  
# events     4     11     0  
DRUG ABUSE † 1      
# participants affected / at risk     2/34 (5.88%)     0/64 (0.00%)     0/4 (0.00%)  
# events     2     0     0  
INSOMNIA † 1      
# participants affected / at risk     9/34 (26.47%)     15/64 (23.44%)     0/4 (0.00%)  
# events     12     17     0  
NERVOUSNESS † 1      
# participants affected / at risk     1/34 (2.94%)     1/64 (1.56%)     1/4 (25.00%)  
# events     1     1     1  
SLEEP DISORDER † 1      
# participants affected / at risk     1/34 (2.94%)     5/64 (7.81%)     0/4 (0.00%)  
# events     1     5     0  
Reproductive system and breast disorders        
METRORRHAGIA † 1      
# participants affected / at risk     2/34 (5.88%)     0/64 (0.00%)     0/4 (0.00%)  
# events     2     0     0  
Respiratory, thoracic and mediastinal disorders        
COUGH † 1      
# participants affected / at risk     6/34 (17.65%)     9/64 (14.06%)     0/4 (0.00%)  
# events     6     10     0  
DYSPNOEA † 1      
# participants affected / at risk     2/34 (5.88%)     5/64 (7.81%)     0/4 (0.00%)  
# events     2     5     0  
DYSPNOEA EXERTIONAL † 1      
# participants affected / at risk     2/34 (5.88%)     5/64 (7.81%)     0/4 (0.00%)  
# events     2     5     0  
OROPHARYNGEAL PAIN † 1      
# participants affected / at risk     2/34 (5.88%)     5/64 (7.81%)     0/4 (0.00%)  
# events     2     7     0  
PRODUCTIVE COUGH † 1      
# participants affected / at risk     2/34 (5.88%)     0/64 (0.00%)     0/4 (0.00%)  
# events     2     0     0  
Skin and subcutaneous tissue disorders        
ALOPECIA † 1      
# participants affected / at risk     6/34 (17.65%)     12/64 (18.75%)     0/4 (0.00%)  
# events     6     12     0  
DRY SKIN † 1      
# participants affected / at risk     3/34 (8.82%)     8/64 (12.50%)     0/4 (0.00%)  
# events     4     11     0  
ERYTHEMA † 1      
# participants affected / at risk     1/34 (2.94%)     4/64 (6.25%)     0/4 (0.00%)  
# events     1     4     0  
PRURITUS † 1      
# participants affected / at risk     3/34 (8.82%)     13/64 (20.31%)     1/4 (25.00%)  
# events     4     16     1  
RASH † 1      
# participants affected / at risk     0/34 (0.00%)     5/64 (7.81%)     0/4 (0.00%)  
# events     0     5     0  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 15.0



  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
No text entered.


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