Vaniprevir Administered With Pegylated-interferon and Ribavirin in Japanese Treatment-Naïve Chronic Hepatitis C Participants (MK-7009-043)

NCT01370642 | Completed Phase 3 Results DMC

• 1 other identifier: 7009-043
• Study Type: interventional
• Target: 294
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and efficacy of vaniprevir given in combination with pegylated interferon alfa-2b (peg-IFN) and ribavirin (RBV) versus treatment with peg-IFN and RBV alone in Japanese treatment-naïve participants with chronic hepatitis C (CHC) genotype (GT)1. 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 arms is superior to the percentage of participants achieving SVR24 in the control arm.

Conditions

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completion of All Study Therapy (SVR24)

  SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy.

  24 weeks after 24 or 48 weeks of study therapy (up to 72 weeks)

• Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study

  An adverse experience 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 adverse experience. For this study, safety parameters or AEs of special interest that were identified a priori constituted "Tier 1" safety endpoints that were subject to inferential testing for statistical significance. Tier 1 AEs on this study included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal adverse (GI) experiences (vomiting, nausea, and diarrhea).

  From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 72 weeks)

• Percentage of Participants Who Discontinued Study Drug Due to an AE

  An adverse experience 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 adverse experience.

  From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 72 weeks)

Secondary Outcomes (5)

• Percentage of Participants Achieving SVR12

  12 weeks after 24 or 48 weeks of study therapy (up to 60 weeks)

• Percentage of Participants Achieving Rapid Virologic Response (RVR)

  At Week 4

• Percentage of Participants Achieving Complete Early Virologic Response (cEVR)

  At Week 12

• Percentage of Participants Achieving Undetectable HCV RNA at the End of Treatment (EOT)

  At Week 24 or 48

• Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10)

  Baseline, Week 2, Week 4, Week 8, Week 12, Week 24

Study Arms (3)

Vaniprevir 12 Week Arm

EXPERIMENTAL

Participants on this arm receive 12 weeks of vaniprevir (300 mg twice daily) and then 12 weeks of placebo to vaniprevir along with 24 weeks of treatment with peg-IFN and RBV.

Drug: vaniprevir; Drug: Placebo to vaniprevir; Biological: Peg-IFN; Drug: ribavirin

Vaniprevir 24 Week Arm

EXPERIMENTAL

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; Biological: Peg-IFN; Drug: ribavirin

Control Arm

ACTIVE COMPARATOR

Participants on this arm receive 24 weeks of treatment with placebo to vaniprevir along with 48 weeks of treatment with peg-IFN and RBV.

Drug: Placebo to vaniprevir; Biological: Peg-IFN; Drug: ribavirin

Interventions

vaniprevir DRUG

Capsules containing 150 mg vaniprevir, orally, two in the morning and two in the evening for 12 or 24 weeks

Also known as: MK-7009

Vaniprevir 12 Week Arm; Vaniprevir 24 Week Arm

Placebo to vaniprevir DRUG

Placebo to vaniprevir, capsules, orally, twice daily for 12 weeks or 24 weeks

Control Arm; Vaniprevir 12 Week Arm

Peg-IFN BIOLOGICAL

Peg-IFN 1.5 μg/kg once per week, subcutaneously (SC) for 24 or 48 weeks

Also known as: PegIntron

Control Arm; Vaniprevir 12 Week Arm; Vaniprevir 24 Week Arm

ribavirin DRUG

Capsules containing 200 mg RBV orally, 3 to 5 capsules, dosage based on the participant's weight (600 mg/day to 1000 mg/day), for 24 or 48 weeks

Also known as: REBETOL®

Control Arm; Vaniprevir 12 Week Arm; Vaniprevir 24 Week Arm

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• IFN treatment naive
• No evidence of cirrhosis

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• Hayashi N, Nakamuta M, Takehara T, Kumada H, Takase A, Howe AY, Ludmerer SW, Mobashery N. Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-naive Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase III study. J Gastroenterol. 2016 Apr;51(4):390-403. doi: 10.1007/s00535-015-1120-x. Epub 2015 Sep 25.

  PMID: 26403160 RESULT

• Ludmerer SW, Hirano T, Black S, Howe AY, Chang W, Takase A, Nakamura K, Tanaka Y, Kumada H, Hayashi N, Nickle D. HCV evolutionary genetics of SVR versus virologic failure assessed from the vaniprevir phase III registration trials. Antiviral Res. 2016 Jun;130:118-29. doi: 10.1016/j.antiviral.2016.03.004. Epub 2016 Mar 3.

  PMID: 26947564 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

vaniprevir; peginterferon alfa-2b; Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2011
• First Posted: June 10, 2011
• Study Start: June 27, 2011
• Primary Completion: July 31, 2013
• Study Completion: March 17, 2014
• Last Updated: October 18, 2018
• Results First Posted: October 6, 2014

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share