Vaniprevir Plus PegIntron®/Ribavirin in Japanese Participants With Chronic Hepatitis C Who Are Non-responders to Previous Treatment (MK-7009-045)

NCT01405560 | Completed Phase 3 Results DMC

• 1 other identifier: 7009-045
• Study Type: interventional
• Target: 42
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and efficacy of vaniprevir (300 mg twice daily) given in combination with pegylated interferon alfa-2b (peg-IFN) and ribavirin (RBV) in Japanese participants with chronic hepatitis C (CHC) genotype (GT) 1 who have not responded to previous treatment. The primary efficacy objective is to estimate efficacy of vaniprevir, peg-IFN and RBV for 24 weeks as assessed by the percentage of participants achieving undetectable Hepatitis C Virus ribonucleic acid (HCV RNA) 24 weeks after completion of all study therapy (Sustained Viral Response 24 \[SVR24\]).

Conditions

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Achieving Sustained Virologic Response (SVR)24

  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.

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

• Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study

  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 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.

  From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)

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

  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.

  From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)

Secondary Outcomes (5)

• Percentage of Participants Achieving SVR12

  12 weeks after 24 weeks of study therapy (up to 36 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 Ribonucleic Acid (RNA) at the End of Treatment (EOT)

  At Week 24

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

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

Study Arms (1)

Vaniprevir 24 Week Arm

EXPERIMENTAL

Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment

Drug: 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 24 weeks

Also known as: MK-7009

Vaniprevir 24 Week Arm

peg-IFN BIOLOGICAL

Open-label peg-IFN alfa-2b at 1.5 μg/kg once per week, administered subcutaneously (SC) for 24 weeks

Also known as: PegIntron

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 weeks

Also known as: REBETOL®

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
• 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 (partial responder or null responder)
• 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)

• Kumada H, Mochida S, Suzuki F, Chayama K, Karino Y, Nakamura K, Fujimoto G, Howe AY, Ludmerer SW, Mobashery N. Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-experienced Japanese patients with hepatitis C virus genotype 1 (GT1b) infection: Phase 3 studies. J Gastroenterol Hepatol. 2016 Oct;31(10):1674-1683. doi: 10.1111/jgh.13328.

  PMID: 26936417 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: Vice President, Late Stage 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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2011
• First Posted: July 29, 2011
• Study Start: September 2, 2011
• Primary Completion: March 29, 2013
• Study Completion: March 29, 2013
• Last Updated: October 18, 2018
• Results First Posted: October 9, 2014

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share