Grazoprevir (MK-5172) Administered With Peginterferon and Ribavirin in Treatment-Naïve Participants With Chronic Hepatitis C (MK-5172-003)

August 16, 2018 updated by: Merck Sharp & Dohme LLC

A Randomized, Active-Controlled, Dose-Ranging Estimation Study to Evaluate the Safety, Tolerability, and Efficacy of Different Regimens of MK-5172 When Administered Concomitantly With Peginterferon Alfa-2b and Ribavirin in Treatment-Naïve Patients With Chronic Genotype 1 Hepatitis C Virus Infection

This study will evaluate the safety, tolerability, and antiviral activity of grazoprevir (MK-5172) when administered in combination with peginterferon alfa-2b (Peg-IFN) and ribavirin (RBV) in treatment-naïve (TN) participants with chronic hepatitis C.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Amendment 4 unblinded treatment after an interim analysis for all subsequently enrolled TN participants (the Second Cohort) who were receiving grazoprevir 400 or 800 mg daily, and they were down-dosed to 100 mg daily between Treatment Week (TW) 3 and TW12 for the remainder of the 12-week treatment course.

Amendment 5 allowed treatment-naïve participants with chronic hepatitis C and compensated cirrhosis to be enrolled and receive open-label grazoprevir 100 mg in combination with Peg-IFN and RBV, without a corresponding control arm.

Study Type

Interventional

Enrollment (Actual)

368

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Has previously documented chronic hepatitis C genotype 1 (CHC GT 1) infection
  • Has hepatitis C virus (HCV) ribonucleic acid (RNA value) ≥10,000 IU/mL
  • Body weight ≥40 kg (88 lbs) and ≤125 kg (275 lbs)
  • Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs and symptoms of decompensated liver disease
  • Had a liver biopsy within 3 years of screening or between screening and Day 1 with histology consistent with CHC and no evidence of cirrhosis or hepatocellular carcinoma or no other cause for chronic liver disease (for participants with compensated cirrhosis, any liver biopsy demonstrating cirrhosis regardless of length of time since biopsy)
  • Female of childbearing potential or a male with female sexual partner who is of childbearing potential agrees to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations
  • For participants with compensated cirrhosis, evidence of cirrhosis without evidence of hepatocellular carcinoma (confirmed by ultrasound within 4 weeks prior)

Exclusion Criteria:

  • Is pregnant, breastfeeding, or plans to become pregnant or donate eggs
  • Is human immunodeficiency virus (HIV) positive or known to be co-infected with hepatitis B virus
  • Has received prior approved or investigational treatment for hepatitis C
  • Has evidence of hepatocellular carcinoma or is under evaluation for hepatocellular carcinoma
  • For participants with compensated cirrhosis: alphafetoprotein level of ≥100 ng/mL
  • Has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years
  • Has evidence or history of chronic hepatitis not caused by HCV
  • Is diabetic and/or hypertensive with clinically significant ocular examination findings: retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or any other clinically significant abnormality
  • Has any known medical condition that could interfere with participation in and completion of the study
  • Pre-existing psychiatric condition including but not limited to moderate or severe depression, suicidal or homicidal ideation or attempt, schizophrenia, psychosis, bipolar disorder, post traumatic stress disorder, or mania
  • Is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent
  • Member or family member of study staff

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Grazoprevir 100 mg
TN non-cirrhotic (NC) participants receive Grazoprevir 100 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.
Drug: Grazoprevir
Orally once daily in AM. Blinded or open-label depending on treatment arm.
Drug: Placebo for Boceprevir
Four capsules orally three times daily.
Drug: Peg-interferon alfa-2b
1.5 μg/kg/week subcutaneous injection.
Other Names:
  • PegIntron
  • Peg-IFN alfa-2b
Drug: Ribavirin
300 mg to 700 mg orally twice daily.
Other Names:
  • Rebetol
Experimental: Grazoprevir 200 mg
TN NC participants receive Grazoprevir 200 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.
Drug: Grazoprevir
Orally once daily in AM. Blinded or open-label depending on treatment arm.
Drug: Placebo for Boceprevir
Four capsules orally three times daily.
Drug: Peg-interferon alfa-2b
1.5 μg/kg/week subcutaneous injection.
Other Names:
  • PegIntron
  • Peg-IFN alfa-2b
Drug: Ribavirin
300 mg to 700 mg orally twice daily.
Other Names:
  • Rebetol
Experimental: Grazoprevir 400 mg
TN NC participants receive Grazoprevir 400 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.
Drug: Grazoprevir
Orally once daily in AM. Blinded or open-label depending on treatment arm.
Drug: Placebo for Boceprevir
Four capsules orally three times daily.
Drug: Peg-interferon alfa-2b
1.5 μg/kg/week subcutaneous injection.
Other Names:
  • PegIntron
  • Peg-IFN alfa-2b
Drug: Ribavirin
300 mg to 700 mg orally twice daily.
Other Names:
  • Rebetol
Experimental: Grazoprevir 800 mg
TN NC participants receive Grazoprevir 800 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.
Drug: Grazoprevir
Orally once daily in AM. Blinded or open-label depending on treatment arm.
Drug: Placebo for Boceprevir
Four capsules orally three times daily.
Drug: Peg-interferon alfa-2b
1.5 μg/kg/week subcutaneous injection.
Other Names:
  • PegIntron
  • Peg-IFN alfa-2b
Drug: Ribavirin
300 mg to 700 mg orally twice daily.
Other Names:
  • Rebetol
Active Comparator: Boceprevir 800 mg
TN NC participants start a 4 week lead-in with Peg-IFN + RBV, then receive Boceprevir 800 mg + Peg-IFN + RBV for 24 weeks followed by 0 or 20 weeks of Peg-IFN + RBV, based on response guided therapy.
Drug: Peg-interferon alfa-2b
1.5 μg/kg/week subcutaneous injection.
Other Names:
  • PegIntron
  • Peg-IFN alfa-2b
Drug: Ribavirin
300 mg to 700 mg orally twice daily.
Other Names:
  • Rebetol
Drug: Boceprevir
Four 200 mg capsules orally three times daily.
Other Names:
  • Victrelis
Drug: Placebo for Grazoprevir
Orally once daily in AM.
Experimental: Grazoprevir 400 mg/100 mg
As the result of an interim analysis, TN NC participants assigned to the 400 mg grazoprevir group were unblinded and transitioned to 100 mg grazoprevir once daily + Peg-IFN + RBV and will remain in the study.
Drug: Grazoprevir
Orally once daily in AM. Blinded or open-label depending on treatment arm.
Drug: Peg-interferon alfa-2b
1.5 μg/kg/week subcutaneous injection.
Other Names:
  • PegIntron
  • Peg-IFN alfa-2b
Drug: Ribavirin
300 mg to 700 mg orally twice daily.
Other Names:
  • Rebetol
Experimental: Grazoprevir 800 mg/100 mg
As the result of an interim analysis, TN NC participants assigned to the 800 mg grazoprevir group were unblinded and transitioned to 100 mg grazoprevir once daily + Peg-IFN + RBV and will remain in the study.
Drug: Grazoprevir
Orally once daily in AM. Blinded or open-label depending on treatment arm.
Drug: Peg-interferon alfa-2b
1.5 μg/kg/week subcutaneous injection.
Other Names:
  • PegIntron
  • Peg-IFN alfa-2b
Drug: Ribavirin
300 mg to 700 mg orally twice daily.
Other Names:
  • Rebetol
Experimental: OL Grazoprevir 100 mg
TN cirrhotic participants receive open-label Grazoprevir 100 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.
Drug: Grazoprevir
Orally once daily in AM. Blinded or open-label depending on treatment arm.
Drug: Peg-interferon alfa-2b
1.5 μg/kg/week subcutaneous injection.
Other Names:
  • PegIntron
  • Peg-IFN alfa-2b
Drug: Ribavirin
300 mg to 700 mg orally twice daily.
Other Names:
  • Rebetol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Achieving Complete Early Viral Response (cEVR)
Time Frame: After 12 weeks of treatment with grazoprevir/boceprevir
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). cEVR was defined as undetectable HCV RNA (target not detected [TND]) at Week 12. 95% confidence intervals provided based on the Clopper-Pearson method.
After 12 weeks of treatment with grazoprevir/boceprevir
Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days
Time Frame: Treatment period plus the first 14 days of follow-up (up to 50 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 SPONSOR's 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 SPONSOR's product, was also an AE.
Treatment period plus the first 14 days of follow-up (up to 50 weeks)
Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days
Time Frame: Treatment period plus the first 14 days of follow-up (up to 50 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 SPONSOR's 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 SPONSOR's product, was also an AE.
Treatment period plus the first 14 days of follow-up (up to 50 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Time to First Achievement of Undetectable HCV RNA During Treatment
Time Frame: From first dose of study medication until first achievement of undetectable HCV RNA (up to 48 weeks of treatment)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. Undetectable HCV RNA (target not detected [TND]) was defined as below the 9.3 IU/ml limit of detection. Kaplan Meier summary statistics were calculated for each treatment arm.
From first dose of study medication until first achievement of undetectable HCV RNA (up to 48 weeks of treatment)
Percentage of Participants Achieving Rapid Viral Response (RVR)
Time Frame: After 4 weeks of treatment with grazoprevir/boceprevir
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). RVR was defined as undetectable (TND) HCV RNA at Week 4 of study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.
After 4 weeks of treatment with grazoprevir/boceprevir
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12)
Time Frame: 12 weeks after the end of all treatment (up to 60 weeks)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). SVR12 was defined as undetectable (TND) HCV RNA at 12 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.
12 weeks after the end of all treatment (up to 60 weeks)
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24)
Time Frame: 24 weeks after the end of all treatment (up to 72 weeks)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). SVR24 was defined as undetectable (TND) HCV RNA at 24 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.
24 weeks after the end of all treatment (up to 72 weeks)
Percentage of Participants Achieving Undetectable HCV RNA at Week 72
Time Frame: Week 72
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. Undetectable HCV RNA (target not detected [TND]) was defined as below the 9.3 IU/ml limit of detection. 95% confidence intervals provided based on the Clopper-Pearson method.
Week 72

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 27, 2011

Primary Completion (Actual)

January 20, 2013

Study Completion (Actual)

March 10, 2015

Study Registration Dates

First Submitted

May 12, 2011

First Submitted That Met QC Criteria

May 13, 2011

First Posted (Estimate)

May 16, 2011

Study Record Updates

Last Update Posted (Actual)

September 14, 2018

Last Update Submitted That Met QC Criteria

August 16, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5172-003
  • 2011-000759-18 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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