Study of Vaniprevir Plus PegIntron®/Ribavirin in Japanese Participants With Chronic Hepatitis C Who Relapsed After Treatment (MK-7009-044)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01405937
First received: July 28, 2011
Last updated: October 3, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to evaluate the safety, tolerability, and efficacy of vaniprevir given in combination with pegylated interferon alfa-2b (PegIntron®/peg-IFN) and ribavirin (RBV) in chronic hepatitis C (CHC) Genotype I (GT 1) participants who relapsed after previous therapy with interferon-based therapy. The primary efficacy hypothesis is that the percentage of participants achieving sustained virologic response 24 weeks after completion of all study therapy (SVR24) in at least one of the vaniprevir 300 mg twice daily treatment regimens is greater than 20% (historical data of standard of care treatment).


Condition Intervention Phase
Hepatitis C, Chronic
Drug: vaniprevir
Biological: peg-IFN
Drug: ribavirin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Study to Evaluate the Safety, Tolerability, and Efficacy of MK-7009 When Concomitantly Administered With Peginterferon Alfa-2b and Ribavirin in Japanese Patients With Chronic Hepatitis C Infection Who Relapsed After Previous Treatment

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completion of All Study Therapy (SVR24) [ Time Frame: 24 weeks after 24 weeks of study therapy (up to 48 weeks) ] [ Designated as safety issue: No ]
    SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy. The percentage of participants achieving SVR24 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.

  • Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study [ Time Frame: From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks) ] [ Designated as safety issue: Yes ]
    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an AE. For this study, safety parameters or AEs of special interest that were identified a priori included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal (GI) adverse experiences (vomiting, nausea, and diarrhea). The percentage of participants with ≥1 specific AEs were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.

  • Percentage of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks) ] [ Designated as safety issue: Yes ]
    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an AE.


Secondary Outcome Measures:
  • Percentage of Participants Achieving SVR12 [ Time Frame: 12 weeks after 24 weeks of study therapy (up to 36 weeks) ] [ Designated as safety issue: No ]
    SVR12 was defined as having an undetectable HCV RNA level 12 weeks after completion of all study therapy. The percentage of participants achieving SVR12 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.

  • Percentage of Participants Achieving Rapid Virologic Response (RVR) [ Time Frame: At Week 4 ] [ Designated as safety issue: No ]
    RVR was defined as having an undetectable HCV RNA level at Week 4. The percentage of participants achieving RVR were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.

  • Percentage of Participants Achieving Complete Early Virologic Response (cEVR) [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
    cEVR was defined as having an undetectable HCV RNA level at Week 12. The percentage of participants achieving cEVR were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.

  • Percentage of Participants Achieving Undetectable HCV RNA at the End of Treatment (EOT) [ Time Frame: At Week 24 ] [ Designated as safety issue: No ]
    Participants were assessed for undetectable HCV RNA levels at the end of all study therapy. The percentage of participants with undetectable HCV RNA levels at EOT were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.

  • Mean Change From Baseline in HCV RNA (Log 10) [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 24 ] [ Designated as safety issue: No ]
    HCV RNA levels were assessed at baseline (BL) and during treatment weeks 2, 4, 8, 12, and 24 using the Roche TaqMan HCV assay, and transformed to Log 10 values. HCV RNA values below the limit of reliable quantification (LoQ) or the limit of detection (LoD) at any time point were handled as follows (imputations done for computational purposes): values below the LoQ but above the LoD were imputed with the LoQ minus 0.1; values below the LoD were imputed with the value of 0 Log IU/mL. HCV RNA levels below the LoD were considered "undetectable".


Enrollment: 51
Study Start Date: August 2011
Study Completion Date: March 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vaniprevir 12 Week Arm
Participants on this arm receive 12 weeks of vaniprevir (300 mg twice daily) along with 24 weeks of treatment with peg-IFN and RBV
Drug: vaniprevir
vaniprevir capsules containing 150 mg vaniprevir, orally, two in the morning and two in the evening for 12 or 24 weeks
Other Name: MK-7009
Biological: peg-IFN
peg-IFN 1.5 µg/kg once per week, subcutaneously (SC) for 24 weeks
Other Name: PegIntron®
Drug: ribavirin
Capsules containing 200 mg ribavirin, orally, 3 to 5 capsules, dosage based on participant weight (600 mg/day to 1000 mg/day), for 24 weeks
Other Name: REBETOL®
Experimental: Vaniprevir 24 Week Arm
Participants on this arm receive 24 weeks of vaniprevir (300 mg twice daily) along with 24 weeks of treatment with peg-IFN and RBV
Drug: vaniprevir
vaniprevir capsules containing 150 mg vaniprevir, orally, two in the morning and two in the evening for 12 or 24 weeks
Other Name: MK-7009
Biological: peg-IFN
peg-IFN 1.5 µg/kg once per week, subcutaneously (SC) for 24 weeks
Other Name: PegIntron®
Drug: ribavirin
Capsules containing 200 mg ribavirin, orally, 3 to 5 capsules, dosage based on participant weight (600 mg/day to 1000 mg/day), for 24 weeks
Other Name: REBETOL®

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Japanese participant diagnosed with compensated CHC GT 1
  • Absence of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease
  • Has received and tolerated treatment with IFN-based therapy (IFN α, IFN β, or peg-IFN) with or without use of ribavirin, but failed to respond to the prior treatment (relapse or breakthrough)
  • No evidence of cirrhosis

Exclusion Criteria:

  • Co-infection with human immunodeficiency virus (HIV)
  • Positive hepatitis B surface antigen or other evidence of active hepatitis B infection
  • Any other condition that is contraindicated or for which caution is required for treatment with peg-IFN or RBV
  • Any condition or pre-study laboratory abnormality, or history of any illness, that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs, peg-IFN and RBV, to the participant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01405937

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01405937     History of Changes
Other Study ID Numbers: 7009-044
Study First Received: July 28, 2011
Results First Received: October 3, 2014
Last Updated: October 3, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014