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

Hepatitis C, Chronic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01405937
• Other study ID #: 7009-044
• Status: Completed
• Phase: Phase 3
• Start date: August 29, 2011
• Est. completion date: March 12, 2013

Study information

• Verified date: September 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: March 12, 2013
• Est. primary completion date: February 26, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 70 Years

Eligibility

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 a, IFN ß, 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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• vaniprevir
vaniprevir capsules containing 150 mg vaniprevir, orally, two in the morning and two in the evening for 12 or 24 weeks

Biological:
• peg-IFN
peg-IFN 1.5 µg/kg once per week, subcutaneously (SC) for 24 weeks

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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) infectio — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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. 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)
Primary	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 (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.	From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Primary	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	Percentage of Participants Achieving SVR12	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.	12 weeks after 24 weeks of study therapy (up to 36 weeks)
Secondary	Percentage of Participants Achieving Rapid Virologic Response (RVR)	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.	At Week 4
Secondary	Percentage of Participants Achieving Complete Early Virologic Response (cEVR)	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.	At Week 12
Secondary	Percentage of Participants Achieving Undetectable HCV RNA at the End of Treatment (EOT)	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.	At Week 24
Secondary	Mean Change From Baseline in HCV RNA (Log 10)	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".	Baseline, Week 2, Week 4, Week 8, Week 12, Week 24