a study of the combination regimen grazoprevir (mk-5172) and elbasvir (mk-8742) ± ribavirin in participants with chronic hepatitis c (mk-5172-035)

Conditions: Hepatitis C

Summary: this is a study of the safety and efficacy of grazoprevir (mk-5172) in combination with elbasvir (mk-8742) ± ribavirin (rbv). the primary efficacy endpoint will be sustained virologic response 12 weeks after the end of all study therapy (svr12) in each of the treatment arms.

part a is being done in treatment-naïve (tn), genotype 1 (gt1), interferon eligible, non-cirrhotic (n-c) participants with chronic hepatitis c (chc). participants will be assigned randomly to 1 of 2 treatment arms in which they will receive grazoprevir 100 mg once daily (qd) + elbasvir 20 mg or 50 mg qd and twice daily (bid) rbv, or to a treatment arm in which they will receive grazoprevir 100 mg qd + elbasvir 50 mg qd without rbv. treatment will last 12 weeks. in part b, participants with hepatitis c virus (hcv) gt1 and hcv ribonucleic acid (rna) levels of ≥10,000 iu/ml will be randomly assigned to a study arm, based on absence or presence of cirrhosis (c), whether they are tn or had poor response to previous antiviral therapy (null responders \[nr\]), or whether co-infected with human immunodeficiency virus (hiv); these participants will receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) ± rbv. treatment will last 8 to 18 weeks dependent on arm assignment. in part c, tn, n-c participants with hcv gt1b and hcv rna levels of ≥10,000 iu/ml will be randomly assigned to receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) ± rbv. treatment will last 8 weeks. in part d, tn n-c participants with hcv gt3 and hcv rna levels of ≥10,000 iu/ml will be randomly assigned to receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) + rbv for 12 or 18 weeks.

Eligibility criteria:
inclusion criteria: all participants * chc genotype 1 (gt1) virus infection (parts a, b, and c) or gt3 virus infection (part d) * female participants of childbearing potential or male participant with female partners of childbearing potential, must use two acceptable methods of birth control from ≥2 weeks prior to day 1 until ≥6 months after last dose of study drug, or longer if dictated by local regulations part a - 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 advanced fibrosis, cirrhosis and/or hepatocellular carcinoma by biopsy or noninvasive testing (fibroscan and/or fibrotest) parts b, c, and d * treatment naïve with or without cirrhosis, or * prior treatment failure to peg-ifn/ribavirin with or without cirrhosis, or * co-infected with human immunodeficiency virus (hiv) without cirrhosis * absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease * liver disease staging assessment by liver biopsy or noninvasive testing (fibroscan and/or fibrotest) exclusion criteria: all participants * non-gt1 hcv infection (part a, part b, and part c) or a non-gt3 hcv infection (part d) including a mixed gt infection (with a non-gt1 \[part a, part b, and part c\] or non-gt3 \[part d\]) or a non-typeable genotype * evidence of hepatocellular carcinoma (hcc) or is under evaluation for hcc * currently participating or participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another study * diabetic and/or hypertensive with clinically significant ocular examination findings * history of depression associated with hospitalization for depression, electroconvulsive therapy, or resulting in prolonged absence from work and/or significant disruption of daily functions * suicidal or homicidal ideations and/or attempt, or history of severe psychiatric disorders * clinical diagnosis of substance abuse * current history of seizure disorder, stroke, or transient ischemic attack * immunologically mediated disease * chronic pulmonary disease * clinically significant cardiac abnormalities/dysfunction * active clinical gout within the last year * hemoglobinopathy or myelodysplastic syndromes * history of organ transplants including hematopoietic stem cell transplants * poor venous access * indwelling venous catheter * history of gastric surgery or malabsorption disorders * severe concurrent disease * evidence of active or suspected malignancy, or a history of malignancy, ≤5 years before * pregnant, lactating, expecting to conceive or donate eggs * male participant with pregnant female partner * member/family member of the investigational study or sponsor staff directly involved with this study * evidence or history of chronic hepatitis not caused by hcv part a * not treatment-naïve * documented to be hiv positive * taking or planning to take significant inducers or inhibitors of cyp3a4 substrates or herbal supplements 2 weeks prior to start of study medications parts b, c, and d * previously received any hcv direct-acting antivirals * requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial * for participants diagnosed with diabetes mellitus, documented hba1c \>8.5%