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)

NCT ID: NCT01710501

Last Updated: 2021-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-07
• Study Completion Date: 2014-01-29

Brief Summary

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.

Conditions

Chronic Hepatitis C (CHC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Grazoprevir 25 mg + PEG-IFN + RBV

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.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

Grazoprevir tablet, orally, once per day at assigned dose

pegylated interferon alfa-2b

Intervention Type: BIOLOGICAL

1.5 mcg/kg/week, administered as a weekly subcutaneous (SC) injection

Ribavirin

Intervention Type: DRUG

Ribavirin capsule, orally, twice daily, at a dose of 800 to 1400 mg based on participant weight

Placebo

Intervention Type: DRUG

Placebo to match grazoprevir tablets to maintain dose blinding

Grazoprevir 50 mg + PEG-IFN + RBV

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.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

Grazoprevir tablet, orally, once per day at assigned dose

pegylated interferon alfa-2b

Intervention Type: BIOLOGICAL

1.5 mcg/kg/week, administered as a weekly subcutaneous (SC) injection

Ribavirin

Intervention Type: DRUG

Ribavirin capsule, orally, twice daily, at a dose of 800 to 1400 mg based on participant weight

Placebo

Intervention Type: DRUG

Placebo to match grazoprevir tablets to maintain dose blinding

Grazoprevir 100 mg + PEG-IFN + RBV

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.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

Grazoprevir tablet, orally, once per day at assigned dose

pegylated interferon alfa-2b

Intervention Type: BIOLOGICAL

1.5 mcg/kg/week, administered as a weekly subcutaneous (SC) injection

Ribavirin

Intervention Type: DRUG

Ribavirin capsule, orally, twice daily, at a dose of 800 to 1400 mg based on participant weight

Placebo

Intervention Type: DRUG

Placebo to match grazoprevir tablets to maintain dose blinding

Interventions

Grazoprevir

Grazoprevir tablet, orally, once per day at assigned dose

Intervention Type: DRUG

pegylated interferon alfa-2b

1.5 mcg/kg/week, administered as a weekly subcutaneous (SC) injection

Intervention Type: BIOLOGICAL

Ribavirin

Ribavirin capsule, orally, twice daily, at a dose of 800 to 1400 mg based on participant weight

Intervention Type: DRUG

Placebo

Placebo to match grazoprevir tablets to maintain dose blinding

Intervention Type: DRUG

Other Intervention Names

MK-5172; SCH 054031; PegIntron™; PEG-IFN; Rebetol™; RBV

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Lagging M, Brown A, Mantry PS, Ramji A, Weilert F, Vierling JM, Howe A, Gendrano IN 3rd, Hwang P, Zhang B, Wahl J, Robertson M, Mobashery N. Grazoprevir plus peginterferon and ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection: a randomized trial. J Viral Hepat. 2016 Feb;23(2):80-8. doi: 10.1111/jvh.12464. Epub 2015 Sep 10.

Reference Type: RESULT

PMID: 26353843 (View on PubMed)

Other Identifiers

2012-003333-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

5172-038

Identifier Type: -

Identifier Source: org_study_id