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

NCT ID: NCT01353911

Last Updated: 2024-05-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

368 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-06-27

Study Completion Date

2015-03-10

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hepatitis C, Chronic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Grazoprevir

Intervention Type DRUG

Orally once daily in AM. Blinded or open-label depending on treatment arm.

Placebo for Boceprevir

Intervention Type DRUG

Four capsules orally three times daily.

Peg-interferon alfa-2b

Intervention Type DRUG

1.5 μg/kg/week subcutaneous injection.

Ribavirin

Intervention Type DRUG

300 mg to 700 mg orally twice daily.

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.

Group Type EXPERIMENTAL

Grazoprevir

Intervention Type DRUG

Orally once daily in AM. Blinded or open-label depending on treatment arm.

Placebo for Boceprevir

Intervention Type DRUG

Four capsules orally three times daily.

Peg-interferon alfa-2b

Intervention Type DRUG

1.5 μg/kg/week subcutaneous injection.

Ribavirin

Intervention Type DRUG

300 mg to 700 mg orally twice daily.

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.

Group Type EXPERIMENTAL

Grazoprevir

Intervention Type DRUG

Orally once daily in AM. Blinded or open-label depending on treatment arm.

Placebo for Boceprevir

Intervention Type DRUG

Four capsules orally three times daily.

Peg-interferon alfa-2b

Intervention Type DRUG

1.5 μg/kg/week subcutaneous injection.

Ribavirin

Intervention Type DRUG

300 mg to 700 mg orally twice daily.

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.

Group Type EXPERIMENTAL

Grazoprevir

Intervention Type DRUG

Orally once daily in AM. Blinded or open-label depending on treatment arm.

Placebo for Boceprevir

Intervention Type DRUG

Four capsules orally three times daily.

Peg-interferon alfa-2b

Intervention Type DRUG

1.5 μg/kg/week subcutaneous injection.

Ribavirin

Intervention Type DRUG

300 mg to 700 mg orally twice daily.

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.

Group Type ACTIVE_COMPARATOR

Boceprevir

Intervention Type DRUG

Four 200 mg capsules orally three times daily.

Placebo for Grazoprevir

Intervention Type DRUG

Orally once daily in AM.

Peg-interferon alfa-2b

Intervention Type DRUG

1.5 μg/kg/week subcutaneous injection.

Ribavirin

Intervention Type DRUG

300 mg to 700 mg orally twice daily.

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.

Group Type EXPERIMENTAL

Grazoprevir

Intervention Type DRUG

Orally once daily in AM. Blinded or open-label depending on treatment arm.

Peg-interferon alfa-2b

Intervention Type DRUG

1.5 μg/kg/week subcutaneous injection.

Ribavirin

Intervention Type DRUG

300 mg to 700 mg orally twice daily.

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.

Group Type EXPERIMENTAL

Grazoprevir

Intervention Type DRUG

Orally once daily in AM. Blinded or open-label depending on treatment arm.

Peg-interferon alfa-2b

Intervention Type DRUG

1.5 μg/kg/week subcutaneous injection.

Ribavirin

Intervention Type DRUG

300 mg to 700 mg orally twice daily.

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.

Group Type EXPERIMENTAL

Grazoprevir

Intervention Type DRUG

Orally once daily in AM. Blinded or open-label depending on treatment arm.

Peg-interferon alfa-2b

Intervention Type DRUG

1.5 μg/kg/week subcutaneous injection.

Ribavirin

Intervention Type DRUG

300 mg to 700 mg orally twice daily.

Interventions

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Grazoprevir

Orally once daily in AM. Blinded or open-label depending on treatment arm.

Intervention Type DRUG

Boceprevir

Four 200 mg capsules orally three times daily.

Intervention Type DRUG

Placebo for Grazoprevir

Orally once daily in AM.

Intervention Type DRUG

Placebo for Boceprevir

Four capsules orally three times daily.

Intervention Type DRUG

Peg-interferon alfa-2b

1.5 μg/kg/week subcutaneous injection.

Intervention Type DRUG

Ribavirin

300 mg to 700 mg orally twice daily.

Intervention Type DRUG

Other Intervention Names

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Victrelis PegIntron Peg-IFN alfa-2b Rebetol

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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Manns MP, Vierling JM, Bacon BR, Bruno S, Shibolet O, Baruch Y, Marcellin P, Caro L, Howe AY, Fandozzi C, Gress J, Gilbert CL, Shaw PM, Cooreman MP, Robertson MN, Hwang P, Dutko FJ, Wahl J, Mobashery N. The combination of MK-5172, peginterferon, and ribavirin is effective in treatment-naive patients with hepatitis C virus genotype 1 infection without cirrhosis. Gastroenterology. 2014 Aug;147(2):366-76.e6. doi: 10.1053/j.gastro.2014.04.006. Epub 2014 Apr 12.

Reference Type RESULT
PMID: 24727022 (View on PubMed)

Howe AY, Black S, Curry S, Ludmerer SW, Liu R, Barnard RJ, Newhard W, Hwang PM, Nickle D, Gilbert C, Caro L, DiNubile MJ, Mobashery N. Virologic resistance analysis from a phase 2 study of MK-5172 combined with pegylated interferon/ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection. Clin Infect Dis. 2014 Dec 15;59(12):1657-65. doi: 10.1093/cid/ciu696. Epub 2014 Sep 28.

Reference Type DERIVED
PMID: 25266289 (View on PubMed)

Other Identifiers

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2011-000759-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

5172-003

Identifier Type: -

Identifier Source: org_study_id

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