A Study of Different Doses of Grazoprevir (MK-5172) Given With Pegylated Interferon Alfa-2b and Ribavirin to Treatment-Naïve Participants With Chronic Hepatitis C (MK-5172-038)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis C (CHC)

Treatments: Drug: Ribavirin; Drug: Grazoprevir; Drug: Placebo; Biological: pegylated interferon alfa-2b

Study type: Interventional

Funder types: Industry

Identifiers

NCT01710501

5172-038

2012-003333-42 (EudraCT Number)

Details and patient eligibility

About

This is a study designed to compare the safety and efficacy of 3 different doses of grazoprevir (MK-5172) combined with pegylated interferon alfa-2b (PEG-IFN) and ribavirin (RBV) in treatment-naïve participants with genotype 1 (GT1) chronic hepatitis C (CHC). Participants will receive 12 weeks of treatment with grazoprevir combined with Peg-IFN and RBV, and depending on response at Week 4 may go on to receive an additional 12 weeks of treatment with Peg-IFN and RBV.

Enrollment: 87 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Treatment naive
• Chronic, compensated HCV GT1 infection
• Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or cirrhosis
• No evidence of cirrhosis or hepatocellular carcinoma by biopsy or noninvasive testing (e.g. FibroScan and/or FibroTest)
• Must agree to use two acceptable methods of birth control from at least 2 weeks prior to first dose and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations

Exclusion criteria

• Non-GT1 HCV infection, including a mixed GT infection (with a non-GT1) or a non-typeable genotype.
• Documented to be Human Immunodeficiency Virus (HIV) positive or co-infected with hepatitis B virus
• Hepatocellular carcinoma (HCC) or under evaluation for HCC
• Participating in or has participated in a study with an investigational compound or device within 30 days of signing informed consent
• Diabetic and/or hypertensive with clinically significant ocular examination findings
• Current or history of central nervous system trauma, seizure disorder, stroke or transient ischemic attack
• Chronic pulmonary disease
• Current or history of any clinically significant cardiac abnormalities/dysfunction
• Active clinical gout within the last year
• History of gastric surgery or history of malabsorption disorders
• Active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin)
• Pregnant, lactating, expecting to conceive or donate eggs, or male participant planning to impregnate or provide sperm donation or with a female partner who is pregnant
• Current moderate or severe depression or history of depression associated with hospitalization, electroconvulsive therapy, or severe disruption of daily functions, or suicidal or homicidal ideation and/or attempt, or history of severe psychiatric disorders
• Evidence or history of chronic hepatitis not caused by HCV

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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87 participants in 3 patient groups

Grazoprevir 25 mg + PEG-IFN + RBV

Experimental group

Description:

After a maximum of a 45 day screening window, randomized participants receive 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by Response Guided Therapy (RGT). Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their Hepatitis C virus ribonucleic acid (HCV RNA) level at Treatment Week (TW) 4.

Treatment:

Biological: pegylated interferon alfa-2b

Drug: Grazoprevir

Drug: Ribavirin

Drug: Placebo

Grazoprevir 50 mg + PEG-IFN + RBV

Experimental group

Description:

After a maximum of a 45 day screening window, randomized participants receive 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4.

Treatment:

Biological: pegylated interferon alfa-2b

Drug: Grazoprevir

Drug: Ribavirin

Drug: Placebo

Grazoprevir 100 mg + PEG-IFN + RBV

Experimental group

Description:

After a maximum of a 45 day screening window, randomized participants receive 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4.

Treatment:

Biological: pegylated interferon alfa-2b

Drug: Grazoprevir

Drug: Ribavirin

Drug: Placebo