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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Hepatitis C, Chronic

Treatments: Drug: Ribavirin; Drug: Grazoprevir; Drug: Peg-interferon alfa-2b; Drug: Placebo for Boceprevir; Drug: Placebo for Grazoprevir; Drug: Boceprevir

Study type: Interventional

Funder types: Industry

Identifiers

NCT01353911

2011-000759-18 (EudraCT Number)

5172-003

Details and patient eligibility

About

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.

Full 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.

Enrollment: 368 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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368 participants in 8 patient groups

Grazoprevir 100 mg

Experimental group

Description:

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.

Treatment:

Drug: Grazoprevir

Drug: Placebo for Boceprevir

Drug: Peg-interferon alfa-2b

Drug: Ribavirin

Grazoprevir 200 mg

Experimental group

Description:

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.

Treatment:

Drug: Grazoprevir

Drug: Placebo for Boceprevir

Drug: Peg-interferon alfa-2b

Drug: Ribavirin

Grazoprevir 400 mg

Experimental group

Description:

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.

Treatment:

Drug: Grazoprevir

Drug: Placebo for Boceprevir

Drug: Peg-interferon alfa-2b

Drug: Ribavirin

Grazoprevir 800 mg

Experimental group

Description:

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.

Treatment:

Drug: Grazoprevir

Drug: Placebo for Boceprevir

Drug: Peg-interferon alfa-2b

Drug: Ribavirin

Boceprevir 800 mg

Active Comparator group

Description:

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.

Treatment:

Drug: Boceprevir

Drug: Placebo for Grazoprevir

Drug: Peg-interferon alfa-2b

Drug: Ribavirin

Grazoprevir 400 mg/100 mg

Experimental group

Description:

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.

Treatment:

Drug: Grazoprevir

Drug: Peg-interferon alfa-2b

Drug: Ribavirin

Grazoprevir 800 mg/100 mg

Experimental group

Description:

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.

Treatment:

Drug: Grazoprevir

Drug: Peg-interferon alfa-2b

Drug: Ribavirin

OL Grazoprevir 100 mg

Experimental group

Description:

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.

Treatment:

Drug: Grazoprevir

Drug: Peg-interferon alfa-2b

Drug: Ribavirin