Safety and Efficacy of SCH 503034 in Previously Untreated Subjects With Chronic Hepatitis C Infected With Genotype 1 (Study P03523)

NCT ID: NCT00423670

Last Updated: 2017-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 765 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2008-11-30

Brief Summary

This was an open-label, randomized safety and efficacy trial in adult, treatment-naïve Chronic Hepatitis C (CHC) participants with genotype 1 infection. The study conducted in 2 parts, compared standard-of-care PegIntron (1.5 μg/kg, once weekly [QW]), plus ribavirin (800 to 1400 mg/day), for 48 weeks to five treatment paradigms containing boceprevir (SCH 503034) 800 mg thrice a day (TID). The five treatments included boceprevir (BOC) plus standard-of-care for 28 or 48 weeks, with and without a 4-week lead-in with PegIntron (PEG) and ribavirin (RBV), and exploration of PegIntron plus low-dose ribavirin (400 to 1000 mg/day) plus boceprevir for 48 weeks.

Detailed Description

The study was conducted in 2 parts.

Part 1 of the study had 5 arms using weight based ribavirin 800-1400 mg/day and compared:

• PegIntron and ribavirin for 48 weeks (Arm 1 - Control)
• PegIntron, ribavirin, and boceprevir for 28 weeks (Arm 2)
• Lead-in with PegIntron and ribavirin for 4 weeks followed by PegIntron, ribavirin and boceprevir for 24 weeks (Arm 3)
• PegIntron, ribavirin and boceprevir for 48 weeks (Arm 4)
• Lead-in with PegIntron and ribavirin for 4 weeks, followed by PegIntron, ribavirin and boceprevir for 44 weeks (Arm 5)

Participants from Arm 1 receiving PegIntron and ribavirin that were HCV positive after 24 weeks of treatment had the option to receive boceprevir in combination with PegIntron and ribavirin for an additional 24 weeks. All participants from Arm 1 that started boceprevir after Week 24 formed the crossover arm (Arm 8).

Part 2 of the study assessed the safety and efficacy of low dose ribavirin (400-1000 mg/day) and compared:

• PegIntron, ribavirin (800-1400 mg/day) and boceprevir for 48 weeks (Arm 6)
• PegIntron, low-dose ribavirin (400-1000 mg/day) and boceprevir for 48 weeks (Arm 7)

Follow-up for all participants was up to 72 weeks after randomization.

Conditions

Chronic Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1. PEG +RBV for 48 Wks (Part I)

Participants treated with PegIntron (1.5 μg/kg, once weekly [QW]) and Ribavirin (800 to 1400 mg/day) for 48 weeks.

Participants with detectable HCV-RNA levels after 24 weeks of treatment had the option of crossing over to receive 24 weeks of PegIntron (1.5 μg/kg, QW), Ribavirin (800 to 1400 mg/day), and boceprevir (800 mg three times daily [TID]) for 24 additional weeks. The participants that crossed over to receive boceprevir formed Arm 8. The total treatment duration was up to 54 weeks.

Group Type: ACTIVE_COMPARATOR

peginterferon-alfa 2b (PegIntron)

Intervention Type: DRUG

1.5 μg/kg subcutaneously (SC) once weekly (QW)

ribavirin

Intervention Type: DRUG

200 mg capsules in doses of 800 to 1400 mg/day (based on weight) taken orally divided twice daily

Arm 2. PEG + RBV + BOC for 28 Wks (Part I)

Participants receiving boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.

Group Type: EXPERIMENTAL

boceprevir (SCH 503034)

Intervention Type: DRUG

200 mg capsules taken as 800 mg orally three times daily (TID)

peginterferon-alfa 2b (PegIntron)

Intervention Type: DRUG

1.5 μg/kg subcutaneously (SC) once weekly (QW)

ribavirin

Intervention Type: DRUG

200 mg capsules in doses of 800 to 1400 mg/day (based on weight) taken orally divided twice daily

Arm 3. PEG + RBV + BOC (from Wk 4) for 24 Wks (Part I)

Participants receiving a lead-in treatment with PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks, followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.

Group Type: EXPERIMENTAL

boceprevir (SCH 503034)

Intervention Type: DRUG

200 mg capsules taken as 800 mg orally three times daily (TID)

peginterferon-alfa 2b (PegIntron)

Intervention Type: DRUG

1.5 μg/kg subcutaneously (SC) once weekly (QW)

ribavirin

Intervention Type: DRUG

200 mg capsules in doses of 800 to 1400 mg/day (based on weight) taken orally divided twice daily

Arm 4. PEG +RBV + BOC for 48 Wks (Part I)

Participants receiving boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.

Group Type: EXPERIMENTAL

boceprevir (SCH 503034)

Intervention Type: DRUG

200 mg capsules taken as 800 mg orally three times daily (TID)

peginterferon-alfa 2b (PegIntron)

Intervention Type: DRUG

1.5 μg/kg subcutaneously (SC) once weekly (QW)

ribavirin

Intervention Type: DRUG

200 mg capsules in doses of 800 to 1400 mg/day (based on weight) taken orally divided twice daily

Arm 5. PEG + RBV + BOC (from Wk 4) for 44 Wks (Part I)

Participants receiving a lead-in treatment with PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks, followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.

Group Type: EXPERIMENTAL

boceprevir (SCH 503034)

Intervention Type: DRUG

200 mg capsules taken as 800 mg orally three times daily (TID)

peginterferon-alfa 2b (PegIntron)

Intervention Type: DRUG

1.5 μg/kg subcutaneously (SC) once weekly (QW)

ribavirin

Intervention Type: DRUG

200 mg capsules in doses of 800 to 1400 mg/day (based on weight) taken orally divided twice daily

Arm 6. PEG + RBV + BOC for 48 Wks (Part II)

Participants receiving PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks during Part II of the study. Part II was initiated after participants were fully enrolled for Part I.

Group Type: EXPERIMENTAL

boceprevir (SCH 503034)

Intervention Type: DRUG

200 mg capsules taken as 800 mg orally three times daily (TID)

peginterferon-alfa 2b (PegIntron)

Intervention Type: DRUG

1.5 μg/kg subcutaneously (SC) once weekly (QW)

ribavirin

Intervention Type: DRUG

200 mg capsules in doses of 800 to 1400 mg/day (based on weight) taken orally divided twice daily

Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)

Participants receiving PegIntron (1.5 μg/kg QW), low-dose ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks (Arm 7) during Part II of the study. Part II was initiated after participants were fully enrolled for Part I.

Group Type: EXPERIMENTAL

boceprevir (SCH 503034)

Intervention Type: DRUG

200 mg capsules taken as 800 mg orally three times daily (TID)

peginterferon-alfa 2b (PegIntron)

Intervention Type: DRUG

1.5 μg/kg subcutaneously (SC) once weekly (QW)

ribavirin (low-dose)

Intervention Type: DRUG

200 mg capsules in doses of 400 to 1000 mg/day (based on weight) taken orally divided twice daily

Arm 8. PEG + RBV + BOC (from Wk 24) for 48 Wks (Part I)

Participants that started in Arm 1 and had detectable HCV-RNA levels after 24 weeks of treatment had the option of receiving boceprevir (800 mg TID) with

PegIntron (1.5 μg/kg QW), and ribavirin (800 to 1400 mg/day). Participants that took the option of crossing over to receive PegIntron, ribavirin, and boceprevir (800 mg TID) for 24 additional weeks constitute Arm 8. The total treatment duration was up to 54 weeks.

Group Type: EXPERIMENTAL

boceprevir (SCH 503034)

Intervention Type: DRUG

200 mg capsules taken as 800 mg orally three times daily (TID)

peginterferon-alfa 2b (PegIntron)

Intervention Type: DRUG

1.5 μg/kg subcutaneously (SC) once weekly (QW)

ribavirin

Intervention Type: DRUG

200 mg capsules in doses of 800 to 1400 mg/day (based on weight) taken orally divided twice daily

Interventions

boceprevir (SCH 503034)

200 mg capsules taken as 800 mg orally three times daily (TID)

Intervention Type: DRUG

peginterferon-alfa 2b (PegIntron)

1.5 μg/kg subcutaneously (SC) once weekly (QW)

Intervention Type: DRUG

ribavirin

200 mg capsules in doses of 800 to 1400 mg/day (based on weight) taken orally divided twice daily

Intervention Type: DRUG

ribavirin (low-dose)

200 mg capsules in doses of 400 to 1000 mg/day (based on weight) taken orally divided twice daily

Intervention Type: DRUG

Other Intervention Names

Boceprevir, Victrelis, SCH 503034

Eligibility Criteria

Inclusion Criteria

• Age between 18 and 60 years;
• Body weight between 45 and 125 kg;
• Documented chronic hepatitis C genotype 1;
• Liver biopsy with histology consistent with chronic hepatitis and no other etiology for chronic liver disease within of 5 years of Day 1;
• Participant and participant's partner(s) must each agree to use acceptable methods of contraception 2 weeks prior to Day 1 and at least 6 months after the last dose of study medication;
• Written informed consent.

Exclusion Criteria

Include, but are not limited to, the following:

• Prior treatment for hepatitis C;
• Co-infection with HIV or hepatitis B virus (HBsAg positive);
• Evidence of decompensated liver disease;
• Diabetic and hypertensive participants with clinically significant ocular exam findings;
• Pre-existing psychiatric condition, including but not limited to:

• Current moderate or severe depression;
• History of depression associated with any of the following:

• Hospitalization for depression;
• Electroconvulsive therapy for depression;
• Depression that resulted in a prolonged absence from work and/or significant disruption of daily functions;
• Suicidal or homicidal ideation and/or attempt;
• History of severe psychiatric disorders (including but not limited to schizophrenia, psychosis, bipolar disorder, post-traumatic stress disorder or mania);
• Past history or current use of lithium;
• Past history or current use of antipsychotic drugs for listed conditions.
• Substance abuse within protocol specified timeframes;
• Pre-existing medical conditions that could interfere with the participant's participation in and completion of the study, including but not limited to chronic pulmonary disease, cardiac dysfunction or immunologically-mediated disease;
• Active or suspected malignancy or history of malignancy within the past 5 years;
• Participants who are pregnant or nursing; participants who intend to become pregnant during the study period. Male participants with partners who are, or intend to become, pregnant during the study period.
• Treatment with any investigational drug or participation in any clinical trial 30 days within Screening;
• Hemoglobin <12 g/dL for females and <13 g/dL for males;
• Neutrophils <1500 mm^3; Blacks: <1200/mm^3;
• Platelets <100,000/mm^3;
• Other clinically significant laboratory test abnormalities.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Kwo PY, Lawitz EJ, McCone J, Schiff ER, Vierling JM, Pound D, Davis MN, Galati JS, Gordon SC, Ravendhran N, Rossaro L, Anderson FH, Jacobson IM, Rubin R, Koury K, Pedicone LD, Brass CA, Chaudhri E, Albrecht JK; SPRINT-1 investigators. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. Lancet. 2010 Aug 28;376(9742):705-16. doi: 10.1016/S0140-6736(10)60934-8. Epub 2010 Aug 6.

Reference Type: DERIVED

PMID: 20692693 (View on PubMed)

Other Identifiers

EudraCT No. 2006-002543-92

Identifier Type: -

Identifier Source: secondary_id

P03523

Identifier Type: -

Identifier Source: org_study_id