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)

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

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 Overview

• Status: Completed
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Biological: PegIntron (PEG); Drug: Ribavirin (RBV); Drug: Boceprevir (BOC)

• Study Type: Interventional
• Enrollment (Actual): 357
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1A: PegIntron (PEG) + 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.	Biological: PegIntron (PEG); 1.5 mcg/kg weekly subcutaneously; Drug: Ribavirin (RBV); 200 mg capsules taken twice daily (BID) (total daily dose of 800-1400 mg/day, depending on weight [weight-based dosing {WBD}])
Active Comparator: Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400; 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.	Biological: PegIntron (PEG); 1.5 mcg/kg weekly subcutaneously; Drug: Ribavirin (RBV); 200 mg capsules taken twice daily (BID) (total daily dose of 800-1400 mg/day, depending on weight [weight-based dosing {WBD}]); Drug: Boceprevir (BOC); 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID; Other Names: SCH 503034
Experimental: Arm 2: PegIntron (PEG) + Boceprevir (BOC) 100 (48 weeks); 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.	Biological: PegIntron (PEG); 1.5 mcg/kg weekly subcutaneously; Drug: Boceprevir (BOC); 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID; Other Names: SCH 503034
Experimental: Arm 3: PegIntron (PEG) + Boceprevir (BOC) 200 (48 Weeks); 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.	Biological: PegIntron (PEG); 1.5 mcg/kg weekly subcutaneously; Drug: Boceprevir (BOC); 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID; Other Names: SCH 503034
Experimental: Arm 4: PegIntron (PEG) + Boceprevir (BOC) 400 (48 weeks); 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.	Biological: PegIntron (PEG); 1.5 mcg/kg weekly subcutaneously; Drug: Boceprevir (BOC); 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID; Other Names: SCH 503034
Experimental: Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400; 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.	Biological: PegIntron (PEG); 1.5 mcg/kg weekly subcutaneously; Drug: Ribavirin (RBV); 200 mg capsules taken twice daily (BID) (total daily dose of 800-1400 mg/day, depending on weight [weight-based dosing {WBD}]); Drug: Boceprevir (BOC); 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID; Other Names: SCH 503034
Experimental: Arm 6: PegIntron (PEG) + Boceprevir (BOC) 400 (24 Weeks); 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.	Biological: PegIntron (PEG); 1.5 mcg/kg weekly subcutaneously; Drug: Boceprevir (BOC); 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID; Other Names: SCH 503034
Experimental: Arm 7: PegIntron (PEG) + Boceprevir (BOC) 800; 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.	Biological: PegIntron (PEG); 1.5 mcg/kg weekly subcutaneously; Drug: Boceprevir (BOC); 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID; Other Names: SCH 503034
Experimental: Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800; 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.	Biological: PegIntron (PEG); 1.5 mcg/kg weekly subcutaneously; Drug: Ribavirin (RBV); 200 mg capsules taken twice daily (BID) (total daily dose of 800-1400 mg/day, depending on weight [weight-based dosing {WBD}]); Drug: Boceprevir (BOC); 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID; Other Names: SCH 503034

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Baseline up to Week 73 [24 weeks after end of treatment (EoT)]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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).	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).	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).	From dosing change to end of follow-up (Week 73) (up to 48 weeks)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): July 1, 2007

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 8, 2005
• First Posted (Estimate): September 12, 2005

Study Record Updates

• Last Update Posted (Estimate): October 14, 2015
• Last Update Submitted That Met QC Criteria: October 13, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Protease Inhibitor; Ribavirin; PEG-Intron
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Peginterferon alfa-2b
• Other Study ID Numbers: P03659