Back to results

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

Primary Purpose

Chronic Hepatitis C

Status

Completed

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

boceprevir (SCH 503034)

peginterferon-alfa 2b (PegIntron)

ribavirin

ribavirin (low-dose)

About this trial

This is an interventional treatment trial for Chronic Hepatitis C

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Active Comparator

Experimental

Arm Label

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

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

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

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

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

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

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

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

Arm Description

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT00423670

First Posted

January 17, 2007

Last Updated

March 8, 2017

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT00423670

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

January 2007 (undefined)

Primary Completion Date

August 2008 (Actual)

Study Completion Date

November 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis C

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

765 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Active Comparator

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

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.

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

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.

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

boceprevir (SCH 503034)

Other Intervention Name(s)

Boceprevir, Victrelis, SCH 503034

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

peginterferon-alfa 2b (PegIntron)

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

ribavirin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

ribavirin (low-dose)

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Participants With Sustained Virologic Response (SVR)

Description

Time Frame

From follow-up week (FW) 24 up to end of follow-up (EOF)

Secondary Outcome Measure Information:

Title

Number of Participants With SVR Based on a 4-week lead-in Treatment With PegIntron and Ribavirin

Description

Time Frame

From FW 24 up to EOF

Title

Number of Participants With SVR Based on Duration of Boceprevir Treatment

Description

Time Frame

From FW 24 up to EOF

Title

Number of Participants Negative for HCV-RNA at FW 12

Description

Time Frame

At FW 12

Title

Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization

Description

Time Frame

72 weeks post randomization

Title

Number of Participants With an Early Virologic Response (EVR) That Achieved SVR

Description

Time Frame

At TW 12, and at FW 24 up to EOF

Title

Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR

Description

Time Frame

At FW 12 and FW 24 up to EOF

Title

Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR

Description

Time Frame

At FW 24 up to EOF and at 72 weeks post randomization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

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.

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php

Citations:

PubMed Identifier

20692693

Citation

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. Erratum In: Lancet. 2010 Oct 9;376(9748):1224. SPRINT-1 investigators [added]; multiple investigator names added.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs