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

A Phase III Study to Evaluate the Safety, Tolerability, and Efficacy of MK-7009 When Administered Concomitantly With Peginterferon Alfa-2b and Ribavirin in Japanese Patients With Chronic Hepatitis C Infection Who Were Non-responders to Previous Treatment

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01405560

Enrollment

Registered

2011-07-29

Start date

2011-09-02

Completion date

2013-03-29

Last updated

2018-10-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatitis C, Chronic

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 \[SVR24\]).

Interventions

DRUGVaniprevir

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

BIOLOGICALpeg-IFN

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

DRUGribavirin

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to 70 Years

Healthy volunteers

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 (partial responder or null responder) * 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

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Achieving Sustained Virologic Response (SVR)24	24 weeks after 24 weeks of study therapy (up to 48 weeks)	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	From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)	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.
Percentage of Participants Who Discontinued Study Drug Due to an AE	From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)	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

Measure	Time frame	Description
Percentage of Participants Achieving Undetectable HCV Ribonucleic Acid (RNA) at the End of Treatment (EOT)	At Week 24	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.
Percentage of Participants Achieving SVR12	12 weeks after 24 weeks of study therapy (up to 36 weeks)	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.
Mean Change From Baseline in HCV RNA (Log 10)	Baseline, Week 2, Week 4, Week 8, Week 12, Week 24	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.
Percentage of Participants Achieving Rapid Virologic Response (RVR)	At Week 4	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)	At Week 12	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.

Participant flow

Recruitment details

Japanese patients 20-70 years old (inclusive) with chronic, compensated, genotype 1 Hepatitis C (HCV) infection and HCV ribonucleic acid (RNA) levels ≥5.0 log IU/mL peripheral blood at screening, who had failed to respond to prior interferon treatment, were recruited from 10 sites in Japan.

Pre-assignment details

42 participants were randomized to receive 24 weeks of vaniprevir in combination with 24 weeks of peg-IFN α-2b (peg-IFN) and ribavirin (RBV).

Participants by arm

Arm	Count
Vaniprevir 24 Week Arm Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment	42
Total	42

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Physician Decision	1

Baseline characteristics

Characteristic	Vaniprevir 24 Week Arm
Age, Continuous	57.4 years STANDARD_DEVIATION 9.2
Sex: Female, Male Female	17 Participants
Sex: Female, Male Male	25 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	42 / 42
serious Total, serious adverse events	3 / 42

Outcome results

Primary

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.

Time frame: 24 weeks after 24 weeks of study therapy (up to 48 weeks)

Population: Full Analysis Set (FAS) population; all randomized participants who received at least one dose of study treatment.

Arm	Measure	Value (NUMBER)
Vaniprevir 24 Week Arm	Percentage of Participants Achieving Sustained Virologic Response (SVR)24	61.9 percentage of participants

Primary

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)

Population: All Participants Treated (APaT) Population; all participants receiving at least one dose of study treatment

Arm	Measure	Value (NUMBER)
Vaniprevir 24 Week Arm	Percentage of Participants Who Discontinued Study Drug Due to an AE	2.4 percentage of participants

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 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.

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

Population: All Participants Treated (APaT) Population; all participants receiving at least one dose of study treatment

Arm	Measure	Group	Value (NUMBER)
Vaniprevir 24 Week Arm	Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study	With ≥1 specific AEs	78.6 percentage of participants
Vaniprevir 24 Week Arm	Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study	anaemia	40.5 percentage of participants
Vaniprevir 24 Week Arm	Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study	GI AEs	52.4 percentage of participants
Vaniprevir 24 Week Arm	Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study	neutropenia	40.5 percentage of participants
Vaniprevir 24 Week Arm	Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study	bilirubin increased	7.1 percentage of participants

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.

Time frame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 24