Clinical trial NCT01710501: 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)
Official title: A Phase II Randomized, Dose Ranging, Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of Different Doses of MK-5172 When Administered Concomitantly With Peginterferon Alfa-2b and Ribavirin in Treatment Naïve Subjects With Chronic Hepatitis C Virus Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis C (CHC)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-10-19
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12)
timeFrame: 12 weeks after end of treatment (up to 36 weeks total)
measure: Number of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days
timeFrame: 14 days following last dose of study drug (up to 26 weeks)
measure: Number of Participants Discontinued From Study Treatment Due to AEs During the Treatment Period and First 14 Follow-up Days
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Percentage of Participants Achieving Undetectable HCV RNA During Treatment by Time Point
timeFrame: From Treatment Week (TW) 2 through end of treatment (up to 24 weeks)
measure: Percentage of Participants Achieving HCV RNA <25 IU/mL During Treatment by Time Point
timeFrame: From TW 2 through end of treatment (up to 24 weeks)
measure: Percentage of Participants Achieving SVR4
timeFrame: 4 weeks after end of treatment (up to 28 weeks total)
measure: Percentage of Subjects Achieving SVR24
timeFrame: 24 weeks after end of treatment (up to 48 weeks total)
measure: Number of Participants Developing Post-baseline Antiviral Resistance to Grazoprevir Among Participants Not Achieving SVR24 Response
timeFrame: From Day 1 up to Follow-up Week 24 (up to 48 weeks total)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.