Clinical trial NCT01353911: Grazoprevir (MK-5172) Administered With Peginterferon and Ribavirin in Treatment-Naïve Participants With Chronic Hepatitis C (MK-5172-003)
Official title: A Randomized, Active-Controlled, Dose-Ranging Estimation Study to Evaluate the Safety, Tolerability, and Efficacy of Different Regimens of MK-5172 When Administered Concomitantly With Peginterferon Alfa-2b and Ribavirin in Treatment-Naïve Patients With Chronic Genotype 1 Hepatitis C Virus Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-05-16
Enrollment: 368
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 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Achieving Complete Early Viral Response (cEVR)
timeFrame: After 12 weeks of treatment with grazoprevir/boceprevir
measure: Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days
timeFrame: Treatment period plus the first 14 days of follow-up (up to 50 weeks)
measure: Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days
timeFrame: Treatment period plus the first 14 days of follow-up (up to 50 weeks)
Secondary outcomes:
measure: Median Time to First Achievement of Undetectable HCV RNA During Treatment
timeFrame: From first dose of study medication until first achievement of undetectable HCV RNA (up to 48 weeks of treatment)
measure: Percentage of Participants Achieving Rapid Viral Response (RVR)
timeFrame: After 4 weeks of treatment with grazoprevir/boceprevir
measure: Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12)
timeFrame: 12 weeks after the end of all treatment (up to 60 weeks)
measure: Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24)
timeFrame: 24 weeks after the end of all treatment (up to 72 weeks)
measure: Percentage of Participants Achieving Undetectable HCV RNA at Week 72
timeFrame: Week 72
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.