Boceprevir (SCH 503034) Plus Peg-Intron, With and Without Added Ribavirin, in Patients With Chronic Hepatitis C, Genotype 1, Who Did Not Respond to Previous Treatment With Peginterferon Alfa Plus Ribavirin (Study P03659AM2)(COMPLETED)
- Conditions
- Chronic Hepatitis C
- Interventions
- Registration Number
- NCT00160251
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 357
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 3: PegIntron (PEG) + Boceprevir (BOC) 200 (48 Weeks) Boceprevir (BOC) A single dose of PEG is given first, followed 1 week later by PEG + BOC 200 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 4: PegIntron (PEG) + Boceprevir (BOC) 400 (48 weeks) Boceprevir (BOC) A single dose of PEG is given first, followed 1 week later by PEG + BOC 400 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800 Boceprevir (BOC) By second protocol amendment to P03659, participants from all arms except Arm 1A will be rolled over into PEG + RBV + BOC 800 for the remainder of the treatment period. Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800 Ribavirin (RBV) By second protocol amendment to P03659, participants from all arms except Arm 1A will be rolled over into PEG + RBV + BOC 800 for the remainder of the treatment period. Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400 Boceprevir (BOC) A single dose of PEG is given first, followed 1 week later by PEG + RBV + BOC 400 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 1A: PegIntron (PEG) + Ribavirin (RBV) PegIntron (PEG) A single dose of PEG is given first, followed 1 week later by PEG + RBV for 12 weeks. If HCV-RNA is undetected, PEG + RBV will continue for another 36 weeks. Arm 1A: PegIntron (PEG) + Ribavirin (RBV) Ribavirin (RBV) A single dose of PEG is given first, followed 1 week later by PEG + RBV for 12 weeks. If HCV-RNA is undetected, PEG + RBV will continue for another 36 weeks. Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400 Boceprevir (BOC) A single dose of PEG is given first, followed 1 week later by PEG + RBV for 12 weeks. If HCV-RNA is detectable, BOC 400 mg TID will be added for 36 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400 PegIntron (PEG) A single dose of PEG is given first, followed 1 week later by PEG + RBV for 12 weeks. If HCV-RNA is detectable, BOC 400 mg TID will be added for 36 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400 Ribavirin (RBV) A single dose of PEG is given first, followed 1 week later by PEG + RBV for 12 weeks. If HCV-RNA is detectable, BOC 400 mg TID will be added for 36 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 2: PegIntron (PEG) + Boceprevir (BOC) 100 (48 weeks) Boceprevir (BOC) A single dose of PEG is given first, followed 1 week later by PEB + BOC 100 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 2: PegIntron (PEG) + Boceprevir (BOC) 100 (48 weeks) PegIntron (PEG) A single dose of PEG is given first, followed 1 week later by PEB + BOC 100 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 3: PegIntron (PEG) + Boceprevir (BOC) 200 (48 Weeks) PegIntron (PEG) A single dose of PEG is given first, followed 1 week later by PEG + BOC 200 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 4: PegIntron (PEG) + Boceprevir (BOC) 400 (48 weeks) PegIntron (PEG) A single dose of PEG is given first, followed 1 week later by PEG + BOC 400 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400 PegIntron (PEG) A single dose of PEG is given first, followed 1 week later by PEG + RBV + BOC 400 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400 Ribavirin (RBV) A single dose of PEG is given first, followed 1 week later by PEG + RBV + BOC 400 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 6: PegIntron (PEG) + Boceprevir (BOC) 400 (24 Weeks) Boceprevir (BOC) A single dose of PEG is given first, followed 1 week later by PEG + BOC 400 for 24 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 6: PegIntron (PEG) + Boceprevir (BOC) 400 (24 Weeks) PegIntron (PEG) A single dose of PEG is given first, followed 1 week later by PEG + BOC 400 for 24 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 7: PegIntron (PEG) + Boceprevir (BOC) 800 Boceprevir (BOC) By first protocol amendment to P03659, this non-randomized arm is added. A single dose of PEG is given first, followed 1 week later by PEG + BOC 800 for 24 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 7: PegIntron (PEG) + Boceprevir (BOC) 800 PegIntron (PEG) By first protocol amendment to P03659, this non-randomized arm is added. A single dose of PEG is given first, followed 1 week later by PEG + BOC 800 for 24 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period. Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800 PegIntron (PEG) By second protocol amendment to P03659, participants from all arms except Arm 1A will be rolled over into PEG + RBV + BOC 800 for the remainder of the treatment period.
- Primary Outcome Measures
Name Time Method Percent of Participants Who Were Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Negative at the End of Treatment (EoT) Baseline up to Week 49 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.Percent of Participants Who Achieved Sustained Virologic Response (SVR) Baseline up to Week 73 [24 weeks after end of treatment (EoT)] 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.
- Secondary Outcome Measures
Name Time Method Percent of Participants Who Achieved Sustained Viral Response (SVR) by Time to First Negative HCV-RNA Baseline up to Week 73 [24 weeks after EoT] 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.
Percentage of Participants Who Were HCV-RNA Negative at EoT After Receiving 1 Week of Treatment With PegIntron (PEG) by Log Drop Week 1 and Week 49 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.Percent of Participants With Virologic Response Prior to Amendment 2 Week 3, Week 5, Week 13 Virologic response was defined as the percentage of participants with Hepatitis C Virus Ribonucleic Acid (HCV-RNA) ≤10,000 IU/mL.
Peak Plasma Concentration of Boceprevir (BOC) All visits during treatment (baseline to Week 49) except Day 1 of Week 1 All plasma samples were assayed using a validated liquid chromatography with tandem mass spectrometric detection (LCMS/MS) method.
Area Under the Plasma Concentration-time Curve of Boceprevir Plasma Concentration for an 8-hour Dosing Period All visits during treatment (baseline to Week 49) except Day 1 of Week 1 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.Trough Plasma Concentration Level All visits during treatment (baseline to Week 49) except Day 1 of Week 1 All plasma samples were assayed using a validated liquid chromatography with tandem mass spectrometric detection (LCMS/MS) method.
Change in Alanine Aminotransferase (ALT) Levels Baseline up to dosing change (> 25 weeks) Change in ALT levels during initial treatment regimen and after rolling into amendment 2 as compared to baseline.
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]) From dosing change to end of follow-up (Week 73)(up to 48 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).
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) From dosing change to end of follow-up (Week 73)(up to 48 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).
Number of Participants Who Were HCV-RNA Negative During Amendment 2 (AM2) for Those Who Started on PegIntron (PEG) + Boceprevir (BOC) 800 (Arm 7) From dosing change to end of follow-up (Week 73) (up to 48 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).