The primary objective of this study is to determine the safe and effective dose range of boceprevir (SCH 503034) in combination with PEG-Intron in adult subjects who have chronic hepatitis C without cirrhosis, and who have failed an adequate course of combination therapy with peginterferon-alfa plus ribavirin. A secondary objective is to explore whether ribavirin provides an additional benefit when combined with PEG-Intron plus boceprevir.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
357
100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID
1.5 mcg/kg weekly subcutaneously
200 mg capsules taken twice daily (BID) (total daily dose of 800-1400 mg/day, depending on weight \[weight-based dosing {WBD}\])
Percent of Participants Who Were Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Negative at the End of Treatment (EoT)
Sustained Viral Response (SVR) was defined as the percentage of participants with HCV-RNA undetectable at the follow-up Week 24. All percentages were based on the total number of participants originally randomized/enrolled to that particular arm. For Arm 1B, the denominator for the percentages was the number who received at least 1 dose of BOC. Arm 1A was not analyzed.
Time frame: Baseline up to Week 49
Percent of Participants Who Achieved Sustained Virologic Response (SVR)
SVR was defined as the percentage of participants with Hepatitis C Virus Ribonucleic Acid (HCV-RNA) undetectable at the follow-up Week 24. All percentages were based on the total number of participants originally randomized/enrolled to that particular arm. For Arm 1B, the denominator for the percentages was the number who received at least 1 dose of BOC. Arm 1A was not analyzed.
Time frame: Baseline up to Week 73 [24 weeks after end of treatment (EoT)]
Percent of Participants Who Achieved Sustained Viral Response (SVR) by Time to First Negative HCV-RNA
Percentage of participants who became HCV-RNA undetectable within the first 13 weeks and subsequently became HCV-RNA positive were not considered negative for this analysis.
Time frame: Baseline up to Week 73 [24 weeks after EoT]
Percentage of Participants Who Were HCV-RNA Negative at EoT After Receiving 1 Week of Treatment With PegIntron (PEG) by Log Drop
For each log drop category (\<0, 0 to 0.5, 0.5 to \<1, 1 to \<1.5, ≥1.5, and Missing), the percentage of participants receiving combination therapy who were HCV-RNA negative at EoT (Week 49) was calculated as follows: Number of participants in a log category who were HCV-RNA negative divided by the total number of participants in that log drop category (n). Percentages were NOT derived using treatment arm N values. The sum of the n values for all 6 log drop categories within a treatment arm equals the overall N for that treatment group.
Time frame: Week 1 and Week 49
Percent of Participants With Virologic Response Prior to Amendment 2
Virologic response was defined as the percentage of participants with Hepatitis C Virus Ribonucleic Acid (HCV-RNA) ≤10,000 IU/mL.
Time frame: Week 3, Week 5, Week 13
Peak Plasma Concentration of Boceprevir (BOC)
All plasma samples were assayed using a validated liquid chromatography with tandem mass spectrometric detection (LCMS/MS) method.
Time frame: All visits during treatment (baseline to Week 49) except Day 1 of Week 1
Area Under the Plasma Concentration-time Curve of Boceprevir Plasma Concentration for an 8-hour Dosing Period
All plasma samples were assayed using a validated liquid chromatography with tandem mass spectrometric detection (LCMS/MS) method. The dosing interval of 8 hours is represented as the hr in the unit of measure.
Time frame: All visits during treatment (baseline to Week 49) except Day 1 of Week 1
Trough Plasma Concentration Level
All plasma samples were assayed using a validated liquid chromatography with tandem mass spectrometric detection (LCMS/MS) method.
Time frame: All visits during treatment (baseline to Week 49) except Day 1 of Week 1
Change in Alanine Aminotransferase (ALT) Levels
Change in ALT levels during initial treatment regimen and after rolling into amendment 2 as compared to baseline.
Time frame: Baseline up to dosing change (> 25 weeks)
Number of Participants Who Were HCV-RNA Negative During Amendment 2 (AM2) for Those Who Started on Arms 2 (PEG+BOC 100), 3 (PEG+BOC 200), 4 (PEG+BOC 400 [48 Weeks]), 6 (PEG+BOC 400 [24 Weeks])
Log drop at baseline of dosing change = difference of log viral loads between baseline (closest to the treatment begin date) and dosing change baseline (virology value closest to the dosing change begin date).
Time frame: From dosing change to end of follow-up (Week 73)(up to 48 weeks)
Number of Participants Who Were HCV-RNA Negative During Amendment 2 (AM2) for Those Who Started on PegIntron (PEG) + Rebetol (RVB) + Boceprevir (BOC) 400 (Arm 5)
Log drop at baseline of dosing change = difference of log viral loads between baseline (closest to the treatment begin date) and dosing change baseline (virology value closest to the dosing change begin date).
Time frame: From dosing change to end of follow-up (Week 73)(up to 48 weeks)
Number of Participants Who Were HCV-RNA Negative During Amendment 2 (AM2) for Those Who Started on PegIntron (PEG) + Boceprevir (BOC) 800 (Arm 7)
Log drop at baseline of dosing change = difference of log viral loads between baseline (closest to the treatment begin date) and dosing change baseline (virology value closest to the dosing change begin date).
Time frame: From dosing change to end of follow-up (Week 73) (up to 48 weeks)
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