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)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis C

Treatments: Drug: Ribavirin (RBV); Drug: Boceprevir (BOC); Biological: PegIntron (PEG)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00160251

P03659

Details and patient eligibility

About

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.

Enrollment: 357 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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357 participants in 9 patient groups

Arm 1A: PegIntron (PEG) + Ribavirin (RBV)

Active Comparator group

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.

Treatment:

Biological: PegIntron (PEG)

Drug: Ribavirin (RBV)

Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400

Active Comparator group

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.

Treatment:

Drug: Boceprevir (BOC)

Biological: PegIntron (PEG)

Drug: Ribavirin (RBV)

Arm 2: PegIntron (PEG) + Boceprevir (BOC) 100 (48 weeks)

Experimental group

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.

Treatment:

Drug: Boceprevir (BOC)

Biological: PegIntron (PEG)

Arm 3: PegIntron (PEG) + Boceprevir (BOC) 200 (48 Weeks)

Experimental group

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.

Treatment:

Drug: Boceprevir (BOC)

Biological: PegIntron (PEG)

Arm 4: PegIntron (PEG) + Boceprevir (BOC) 400 (48 weeks)

Experimental group

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.

Treatment:

Drug: Boceprevir (BOC)

Biological: PegIntron (PEG)

Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400

Experimental group

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.

Treatment:

Drug: Boceprevir (BOC)

Biological: PegIntron (PEG)

Drug: Ribavirin (RBV)

Arm 6: PegIntron (PEG) + Boceprevir (BOC) 400 (24 Weeks)

Experimental group

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.

Treatment:

Drug: Boceprevir (BOC)

Biological: PegIntron (PEG)

Arm 7: PegIntron (PEG) + Boceprevir (BOC) 800

Experimental group

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.

Treatment:

Drug: Boceprevir (BOC)

Biological: PegIntron (PEG)

Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800

Experimental group

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.

Treatment:

Drug: Boceprevir (BOC)

Biological: PegIntron (PEG)

Drug: Ribavirin (RBV)