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

Chronic Hepatitis C Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00423670
• Other study ID #: P03523
• Secondary ID: EudraCT No. 2006
• Status: Completed
• Phase: Phase 2
• First received: January 17, 2007
• Last updated: February 16, 2015
• Start date: January 2007
• Est. completion date: November 2008

Study information

• Verified date: February 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 765
• Est. completion date: November 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• boceprevir (SCH 503034)
200 mg capsules taken as 800 mg orally three times daily (TID)
• peginterferon-alfa 2b (PegIntron)
1.5 µg/kg subcutaneously (SC) once weekly (QW)
• ribavirin
200 mg capsules in doses of 800 to 1400 mg/day (based on weight) taken orally divided twice daily
• ribavirin (low-dose)
200 mg capsules in doses of 400 to 1000 mg/day (based on weight) taken orally divided twice daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Sustained Virologic Response (SVR)	Participants with undetectable HCV-RNA at FW 24 up to EOF had achieved SVR.; Participants missing data at FW 24 were considered to achieve SVR if; he/she had undetectable HCV-RNA at FW 12 or later; he/she returned later to the study center and had undetectable HCV-RNA.; HCV-RNA in plasma samples was detected with reverse-transcriptase-polymerase chain reaction (RT-PCR) assay, with a lower limit of detection (LLD) of 29 international units/mL (IU/mL).; A participant in Arm 2 with undetectable HCV-RNA at FW 24 had detectable HCV-RNA after FW 24. He is not considered to achieve SVR.	From follow-up week (FW) 24 up to end of follow-up (EOF)	No
Secondary	Number of Participants With SVR Based on a 4-week lead-in Treatment With PegIntron and Ribavirin	Number of participants with SVR (undetectable plasma HCV-RNA at FW 24 up to EOF). To assess the effect of lead-in treatment on SVR, participants with (Arm 3 and Arm 5) or without (Arm 2 and Arm 4) lead-in were pooled.; Participants missing data at FW 24 were considered to achieve SVR if; he/she had undetectable HCV-RNA at FW 12 or later; he/she returned later to the study center and had undetectable HCV-RNA.; HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.	From FW 24 up to EOF	No
Secondary	Number of Participants With SVR Based on Duration of Boceprevir Treatment	Number of participants with SVR (undetectable plasma HCV-RNA at FW 24 up to EOF). Participants from treatment arms receiving boceprevir for 28-weeks (Arm 2 and Arm 3) were pooled, and those receiving boceprevir for 48-weeks (Arm 4 and Arm 5) were pooled for the analysis.; Participants missing data at FW 24 were considered to achieve SVR if; he/she had undetectable HCV-RNA at FW 12 or later; he/she returned later to the study center and had undetectable HCV-RNA.; HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.	From FW 24 up to EOF	No
Secondary	Number of Participants Negative for HCV-RNA at FW 12	Participants who had undetectable plasma HCV-RNA at FW 12. Also reported are participants for whom the HCV-RNA values were missing. 36 participant who switched over to Arm 8 from Arm 1, are included in the missing values for Arm 1.; HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.	At FW 12	No
Secondary	Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization	Participants who had undetectable HCV-RNA at 72 weeks post randomization are reported. Participants with missing HCV-RNA values at 72 weeks post randomization are also reported.; HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.	72 weeks post randomization	No
Secondary	Number of Participants With an Early Virologic Response (EVR) That Achieved SVR	Participants with undetectable HCV-RNA at TW 12 have EVR, and with undetectable HCV-RNA at FW 24 (up to EOF) achieved SVR.; Participants missing data at FW 24 were considered to achieve SVR if; he/she had undetectable HCV-RNA at FW 12 or later; if he/she returned later to the study center and had undetectable HCV-RNA.; HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.	At TW 12, and at FW 24 up to EOF	No
Secondary	Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR	Treatment-naïve adults with CHC genotype 1 were assigned study medication. Participants with undetectable HCV-RNA at FW 12 that achieved SVR (have undetectable HCV-RNA at FW 24 (up to EOF) are reported.; Participants missing data at FW 24 were considered to achieve SVR if; he/she had undetectable HCV-RNA at FW 12 or later; if he/she returned later to the study center and had undetectable HCV-RNA.; HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.	At FW 12 and FW 24 up to EOF	No
Secondary	Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR	Participants with undetectable HCV-RNA at 72 weeks post randomization that achieved SVR (have undetectable HCV-RNA at FW 24 up to EOF) are reported.; Participants missing data at FW 24 were considered to achieve SVR if; he/she had undetectable HCV-RNA at FW 12 or later; if he/she returned later to the study center and had undetectable HCV-RNA.; HCV-RNA in plasma samples was detected an the RT-PCR assay. The lower limit of detection (LLD) was 29 IU/mL.	At FW 24 up to EOF and at 72 weeks post randomization	No