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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00423670
First received: January 17, 2007
Last updated: March 17, 2014
Last verified: March 2014

January 17, 2007
March 17, 2014
January 2007
August 2008   (final data collection date for primary outcome measure)
Number of Participants With Sustained Virologic Response (SVR) [ Time Frame: From follow-up week (FW) 24 up to end of follow-up (EOF) ] [ Designated as safety issue: No ]

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

  1. he/she had undetectable HCV-RNA at FW 12 or later
  2. 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.

Not Provided
Complete list of historical versions of study NCT00423670 on ClinicalTrials.gov Archive Site
  • Number of Participants With SVR Based on a 4-week lead-in Treatment With PegIntron and Ribavirin [ Time Frame: From FW 24 up to EOF ] [ Designated as safety issue: No ]

    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

    1. he/she had undetectable HCV-RNA at FW 12 or later
    2. 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.

  • Number of Participants With SVR Based on Duration of Boceprevir Treatment [ Time Frame: From FW 24 up to EOF ] [ Designated as safety issue: No ]

    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

    1. he/she had undetectable HCV-RNA at FW 12 or later
    2. 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.

  • Number of Participants Negative for HCV-RNA at FW 12 [ Time Frame: At FW 12 ] [ Designated as safety issue: No ]

    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.

  • Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization [ Time Frame: 72 weeks post randomization ] [ Designated as safety issue: No ]

    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.

  • Number of Participants With an Early Virologic Response (EVR) That Achieved SVR [ Time Frame: At TW 12, and at FW 24 up to EOF ] [ Designated as safety issue: No ]

    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

    1. he/she had undetectable HCV-RNA at FW 12 or later
    2. 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.

  • Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR [ Time Frame: At FW 12 and FW 24 up to EOF ] [ Designated as safety issue: No ]

    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

    1. he/she had undetectable HCV-RNA at FW 12 or later
    2. 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.

  • Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR [ Time Frame: At FW 24 up to EOF and at 72 weeks post randomization ] [ Designated as safety issue: No ]

    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

    1. he/she had undetectable HCV-RNA at FW 12 or later
    2. 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.

Not Provided
Not Provided
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Safety and Efficacy of SCH 503034 in Previously Untreated Subjects With Chronic Hepatitis C Infected With Genotype 1 (Study P03523)
A Safety and Efficacy Study of SCH 503034 in Previously Untreated Subjects With Chronic Hepatitis C Infected With Genotype 1

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Hepatitis C
  • Drug: boceprevir (SCH 503034)
    200 mg capsules taken as 800 mg orally three times daily (TID)
    Other Name: Boceprevir, Victrelis, SCH 503034
  • Drug: peginterferon-alfa 2b (PegIntron)
    1.5 μg/kg subcutaneously (SC) once weekly (QW)
  • Drug: ribavirin
    200 mg capsules in doses of 800 to 1400 mg/day (based on weight) taken orally divided twice daily
  • Drug: ribavirin (low-dose)
    200 mg capsules in doses of 400 to 1000 mg/day (based on weight) taken orally divided twice daily
  • Active Comparator: 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.

    Interventions:
    • Drug: peginterferon-alfa 2b (PegIntron)
    • Drug: ribavirin
  • Experimental: 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.
    Interventions:
    • Drug: boceprevir (SCH 503034)
    • Drug: peginterferon-alfa 2b (PegIntron)
    • Drug: ribavirin
  • Experimental: 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.
    Interventions:
    • Drug: boceprevir (SCH 503034)
    • Drug: peginterferon-alfa 2b (PegIntron)
    • Drug: ribavirin
  • Experimental: 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.
    Interventions:
    • Drug: boceprevir (SCH 503034)
    • Drug: peginterferon-alfa 2b (PegIntron)
    • Drug: ribavirin
  • Experimental: 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.
    Interventions:
    • Drug: boceprevir (SCH 503034)
    • Drug: peginterferon-alfa 2b (PegIntron)
    • Drug: ribavirin
  • Experimental: 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.
    Interventions:
    • Drug: boceprevir (SCH 503034)
    • Drug: peginterferon-alfa 2b (PegIntron)
    • Drug: ribavirin
  • Experimental: 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.
    Interventions:
    • Drug: boceprevir (SCH 503034)
    • Drug: peginterferon-alfa 2b (PegIntron)
    • Drug: ribavirin (low-dose)
  • Experimental: 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.

    Interventions:
    • Drug: boceprevir (SCH 503034)
    • Drug: peginterferon-alfa 2b (PegIntron)
    • Drug: ribavirin
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. 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. Epub 2010 Aug 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
765
November 2008
August 2008   (final data collection date for primary outcome measure)

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.
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00423670
P03523, EudraCT No. 2006-002543-92
Yes
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP