Back to resultsBoceprevir (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)
Primary Purpose
Chronic Hepatitis C
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Boceprevir (BOC)
PegIntron (PEG)
Ribavirin (RBV)
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis C focused on measuring PEG-Intron, Ribavirin, Protease Inhibitor
Eligibility Criteria
Key inclusion criteria: Documented infection with chronic hepatitis C (CHC), genotype 1. Documented failure to respond to an adequate course of treatment (minimum 12 weeks) with peginterferon-alfa plus ribavirin (failure defined as <2 log drop in HCV-RNA after 12 weeks of therapy or those who never become Hepatitis C Virus Ribonucleic Acid (HCV)-RNA negative) No evidence of cirrhosis on liver biopsy. Results of physical examination and laboratory tests within specified ranges. Abstinence from use of abused substances. Key exclusion criteria: Women who are pregnant or nursing a child. Patients with cirrhosis, co-infection with Hepatitis B or human immunodeficiency virus (HIV), and African-American patients (by protocol amendment 2, African-American patients can enroll). Previous treatment with any Hepatitis C Virus (HCV) polymerase or protease inhibitor. Patients who relapsed following response to previous treatment. Evidence of advanced liver disease, or liver disease from a cause other than CHC. Pre-existing psychiatric condition.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm Type
Active Comparator
Active Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Arm 1A: PegIntron (PEG) + Ribavirin (RBV)
Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400
Arm 2: PegIntron (PEG) + Boceprevir (BOC) 100 (48 weeks)
Arm 3: PegIntron (PEG) + Boceprevir (BOC) 200 (48 Weeks)
Arm 4: PegIntron (PEG) + Boceprevir (BOC) 400 (48 weeks)
Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400
Arm 6: PegIntron (PEG) + Boceprevir (BOC) 400 (24 Weeks)
Arm 7: PegIntron (PEG) + Boceprevir (BOC) 800
Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800
Arm Description
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.
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.
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.
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.
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.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
Peak Plasma Concentration of Boceprevir (BOC)
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 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 plasma samples were assayed using a validated liquid chromatography with tandem mass spectrometric detection (LCMS/MS) method.
Change in Alanine Aminotransferase (ALT) Levels
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])
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)
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)
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).
Full Information
NCT ID
NCT00160251
First Posted
September 8, 2005
Last Updated
October 13, 2015
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT00160251
Brief Title
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)
Official Title
PEG-Intron/REBETOL vs PEG-Intron/ SCH 503034 With and Without Ribavirin in Chronic Hepatitis C Virus Genotype 1 (HCV-1) Peginterferon Alfa/Ribavirin Nonresponders: A SCH 503034 Dose-Finding Phase 2 Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
July 2007 (Actual)
Study Completion Date
July 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C
Keywords
PEG-Intron, Ribavirin, Protease Inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
357 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1A: PegIntron (PEG) + Ribavirin (RBV)
Arm Type
Active Comparator
Arm Description
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 Title
Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400
Arm Type
Active Comparator
Arm Description
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 Title
Arm 2: PegIntron (PEG) + Boceprevir (BOC) 100 (48 weeks)
Arm Type
Experimental
Arm Description
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 Title
Arm 3: PegIntron (PEG) + Boceprevir (BOC) 200 (48 Weeks)
Arm Type
Experimental
Arm Description
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 Title
Arm 4: PegIntron (PEG) + Boceprevir (BOC) 400 (48 weeks)
Arm Type
Experimental
Arm Description
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 Title
Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400
Arm Type
Experimental
Arm Description
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 Title
Arm 6: PegIntron (PEG) + Boceprevir (BOC) 400 (24 Weeks)
Arm Type
Experimental
Arm Description
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 Title
Arm 7: PegIntron (PEG) + Boceprevir (BOC) 800
Arm Type
Experimental
Arm Description
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 Title
Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Boceprevir (BOC)
Other Intervention Name(s)
SCH 503034
Intervention Description
100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID
Intervention Type
Biological
Intervention Name(s)
PegIntron (PEG)
Intervention Description
1.5 mcg/kg weekly subcutaneously
Intervention Type
Drug
Intervention Name(s)
Ribavirin (RBV)
Intervention Description
200 mg capsules taken twice daily (BID) (total daily dose of 800-1400 mg/day, depending on weight [weight-based dosing {WBD}])
Primary Outcome Measure Information:
Title
Percent of Participants Who Were Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Negative at the End of Treatment (EoT)
Description
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
Title
Percent of Participants Who Achieved Sustained Virologic Response (SVR)
Description
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)]
Secondary Outcome Measure Information:
Title
Percent of Participants Who Achieved Sustained Viral Response (SVR) by Time to First Negative HCV-RNA
Description
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]
Title
Percentage of Participants Who Were HCV-RNA Negative at EoT After Receiving 1 Week of Treatment With PegIntron (PEG) by Log Drop
Description
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
Title
Percent of Participants With Virologic Response Prior to Amendment 2
Description
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
Title
Peak Plasma Concentration of Boceprevir (BOC)
Description
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
Title
Area Under the Plasma Concentration-time Curve of Boceprevir Plasma Concentration for an 8-hour Dosing Period
Description
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
Title
Trough Plasma Concentration Level
Description
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
Title
Change in Alanine Aminotransferase (ALT) Levels
Description
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)
Title
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])
Description
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)
Title
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)
Description
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)
Title
Number of Participants Who Were HCV-RNA Negative During Amendment 2 (AM2) for Those Who Started on PegIntron (PEG) + Boceprevir (BOC) 800 (Arm 7)
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key inclusion criteria:
Documented infection with chronic hepatitis C (CHC), genotype 1.
Documented failure to respond to an adequate course of treatment (minimum 12 weeks) with peginterferon-alfa plus ribavirin (failure defined as <2 log drop in HCV-RNA after 12 weeks of therapy or those who never become Hepatitis C Virus Ribonucleic Acid (HCV)-RNA negative)
No evidence of cirrhosis on liver biopsy.
Results of physical examination and laboratory tests within specified ranges.
Abstinence from use of abused substances.
Key exclusion criteria:
Women who are pregnant or nursing a child.
Patients with cirrhosis, co-infection with Hepatitis B or human immunodeficiency virus (HIV), and African-American patients (by protocol amendment 2, African-American patients can enroll).
Previous treatment with any Hepatitis C Virus (HCV) polymerase or protease inhibitor.
Patients who relapsed following response to previous treatment.
Evidence of advanced liver disease, or liver disease from a cause other than CHC.
Pre-existing psychiatric condition.
12. IPD Sharing Statement
Learn more about this trial
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)
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