Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Efficacy, Tolerability, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including PegIFNa-2a and Ribavirin in HCV Genotype 1 Infected Subjects Who Failed Previous Standard Therapy
Brief Summary: The purpose of this study is to determine the efficacy, safety and tolerability of different regimens of TMC435 with standard treatment compared to standard treatment alone in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who has failed previous treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV).


Options:
A: Inclusion Criteria:

* Subjects must have a qualifying regimen defined as peginterferon alfa-2a/ribavirin or peginterferon alfa-2b/ribavirin for a minimum of 12 weeks.
* During the qualifying regimen, subjects must have either:

  * A documented undetectable Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) within 30 days of the end-of-treatment and a subsequent detectable HCV-RNA during follow-up OR
  * A documented decline in HCV-RNA by \>=2 log10 after 12 weeks of treatment.
* Subject must have previously documented chronic hepatitis C genotype 1 infection.
* Subject must have a liver biopsy with histology consistent with chronic hepatitis C infection and no other etiology.
* Subjects with bridging fibrosis or cirrhosis must have an ultrasound within 6 months with no findings suspicious for hepatocellular carcinoma (HCC).
* Subject must be \>=18 years of age.
* Subject must weigh between 40 kg and 125 kg.
* Subject and subject's partner(s) must each agree to use acceptable methods of contraception.
* Subjects must be willing to give written informed consent.

Exclusion Criteria:

Subject will be excluded from entry if ANY of the criteria listed below are

met:

* Subjects known to be coinfected with the human immunodeficiency virus (HIV) or hepatitis B virus (hepatitis B surface antigen \[HBsAg\] positive) and/or demonstrating signs and symptoms consistent with co-infection.
* Subjects who required discontinuation of previous interferon or ribavirin regimen for an adverse event considered by the investigator to be possibly or probably related to ribavirin and/or interferon.
* Treatment with ribavirin within 90 days and any interferon alfa within 1 month of Screening.
* Treatment for hepatitis C with any investigational medication. Prior treatment with herbal remedies with known hepatotoxicity is exclusionary.
* Treatment with any investigational drug within 30 days of the randomization visit in this study.
* Participation in any other clinical trial within 30 days of randomization or intention to participate in another clinical trial during participation in this study.
* Evidence of decompensated liver disease.
* Diabetic and/or hypertensive subjects with clinically significant ocular examination findings.
* Pre-existing psychiatric condition(s).
* Clinical diagnosis of substance abuse.
* Any known pre-existing medical condition that could interfere with the subject's participation in and completion of the study.
* Evidence of 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).
* Subjects who are pregnant or nursing. Subjects who intend to become pregnant during the study period. Male subjects with partners who are or who intend to become pregnant during the study period.
* Any other condition which, in the opinion of a physician, would make the subject unsuitable for enrollment or could interfere with the subject participating in and completing the study.
* Subjects who are part of the site personnel directly involved with this study.
* Subjects who are family members of the investigational study staff.
* Subjects who had a life-threatening serious adverse event (SAE) during the screening period.
* Subjects with a history of pancreatitis, except for one episode clearly secondary to gallstone.

Laboratory Exclusion Criteria:

* Hematologic, biochemical, and serologic criteria (growth factors may not be used to achieve study entry requirements):

  * Hemoglobin (Hgb) \<12 g/dL for females and \<13 g/dL for males
  * Neutrophils \<1500/mm3 (blacks: \<1200/mm3)
  * Platelets \<100,000/mm3
  * Direct bilirubin \>1.5 x upper limit of normal (ULN) of the laboratory reference range. Total bilirubin \>1.6 mg/dL unless the subject has a history of Gilbert's disease. If Gilbert's disease is the proposed etiology, this must be documented in the subject's chart.
* Serum albumin \< lower limit of normal (LLN) of laboratory reference range.
* Thyroid-stimulating hormone (TSH) \>1.2 x ULN or \<0.8 x LLN of laboratory reference range.
* Serum creatinine \>ULN of the laboratory reference range.
* Serum glucose:

  * For subjects not previously diagnosed with diabetes mellitus:

    * \>=140 mg/dL (nonfasting) unless hemoglobin A1c subtype (HbA1c) \<=7% OR
    * \>=100 mg/dL (fasting) unless HbA1c \<=7%.
  * For subjects previously diagnosed with diabetes mellitus: HbA1c \>8.5%.
* Prothrombin time/partial thromboplastin time (PT/PTT) values \>10% above laboratory reference range.
* Anti-nuclear antibodies (ANA) \>1:320.
* Alpha fetoprotein (AFP):

  * AFP \>100 ng/mL OR
  * AFP 50 to 100 ng/mL requires a liver ultrasound and subjects with findings suspicious for HCC are excluded.
B: Inclusion Criteria:

* Must have chronic hepatitis C infection as evidenced by liver biopsy, anti-hepatitis C virus (HCV) and HCV RNA positive
* Must have chronic hepatitis C infection (genotype 1) with HCV RNA level greater than10000 IU/mL
* Patient must have failed at least 1 prior course of peg interferon (Peg-IFN-alfa-2a)/ribavirin (RBV) therapy (standard treatment)
* Must be willing to use 2 effective methods of birth control for up to 7 months after last dose of study medication

Exclusion Criteria:

* Has an evidence of decompensated liver disease
* Co-infection with any other Hepatitis C virus genotype or co-infection with the human immunodeficiency virus (HIV)
* Has a medical condition which is a contraindication to Peg-INF or RBV therapy
* Have had history of, or any current medical condition which could impact the safety of the patient in the study
C: Inclusion Criteria:

* Body Mass Index (BMI) of 18 to ≤ 37 kg/m\^2
* Clinical diagnosis of chronic HCV infection defined by positive serology for HCV for at least 6 months and detectable HCV RNA in peripheral blood ≥105 IU/mL at screening
* Participant must be infected with HCV GT1a, GT1b, or GT 3

Exclusion Criteria:

* Co-infection with GT1 and GT3
* Estimated creatinine clearance of ≤70 mL/min based on the Cockcroft-Gault equation
* History of stroke, chronic seizures, or major neurological disorder
* History of clinically significant endocrine, gastrointestinal (excepting HCV infection), cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases
* History of neoplastic disease
* Positive Hepatitis B surface antigen at the pre-study (screening) visit
* Has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks prior to the prestudy (screening) visit.
* Previous treatments (s) with nonstructural protein 5A (NS5A) inhibitors
* \<4 weeks since administration of any experimental protease inhibitor
* Previous exposure to interferon-alpha and/or ribavirin within 3 month prior to the first dose of elbasvir in the study
* Clinical or laboratory evidence of advanced or decompensated liver disease
D: Inclusion Criteria:

* Qualifying regimen defined as pegylated interferon alfa-2a plus ribavirin or pegylated interferon alfa-2b plus ribavirin for a minimum of 12 weeks.
* During qualifying regimen, participants must have either a documented undetectable HCV-RNA within 30 days of end of treatment (EOT) and a subsequent detectable HCV-RNA during follow-up or a documented decline in HCV-RNA by \>=2 log10 by Treatment Week 12
* Previously documented CHC genotype 1 infection.
* Liver biopsy with histology consistent with CHC and no other etiology.
* Participants with bridging fibrosis or cirrhosis must have an ultrasound within 6 months of the Screening Visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma (HCC).
* Participants participating in Schering-Plough Research Institute (SPRI) maintenance protocols P02570 (NCT00049842) or P02569 (NCT00048724) must have completed the study to be eligible for this protocol.
* Participants must be \>=18 years of age.
* Participants must weigh between 40 kg and 125 kg.
* Participants and participant's partner(s) must each agree to use acceptable methods of contraception for 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.
* Participants must be willing to give written informed consent.

Exclusion Criteria:

* Coinfection with the human immunodeficiency virus (HIV) or hepatitis B virus (Hepatitis B Surface Antigen \[HBsAg\] positive).
* Discontinuation of previous interferon or ribavirin regimen for an adverse event (AE) considered by the investigator to be possibly or probably related to ribavirin and/or interferon.
* Treatment with ribavirin within 90 days and any interferon-alpha within 1 month of Screening.
* Treatment for hepatitis C with any investigational medication. Prior treatment with herbal remedies with known hepatotoxicity.
* Treatment with any investigational drug within 30 days of the randomization visit.
* Participation in any other clinical trial within 30 days of randomization or intention to participate in another clinical trial.
* Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy.
* Diabetic and/or hypertensive participants with clinically significant ocular examination findings.
* Pre-existing psychiatric conditions.
* Clinical diagnosis of substance abuse of the specified drugs within the specified timeframes
* Any known pre-existing medical condition that could interfere with the participant's participation in and completion of the study.
* Evidence of 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). Participants under evaluation for malignancy are not eligible.
* Participants who are pregnant or nursing. Participants who intend to become pregnant during the study period. Male participants with partners who are, or intend to become, pregnant during the study period.
* Any other condition which, in the opinion of a physician, would make the participant unsuitable for enrollment or could interfere with the participant participating in and completing the study.
* Participants who are part of the site personnel directly involved with this study.
* Participants who are family members of the investigational study staff.
* Participants who had life-threatening serious adverse event (SAE) during screening period.
* Protocol-specified hematologic, biochemical, and serologic criteria: Hemoglobin \<12 g/dL for females and \<13 g/dL for males; Neutrophils \<1500/mm\^3 (Blacks: \<1200/mm\^3); Platelets \<100,000/mm\^3; Direct bilirubin \>1.5 x upper limit of normal (ULN).
* Serum albumin \<lower limit of normal (LLN)
* Thyroid-stimulating hormone (TSH) \>1.2 x ULN or \<0.8 x LLN of laboratory reference range, with certain exceptions.
* Serum creatinine \>ULN of the laboratory reference.
* Protocol-specified serum glucose concentrations.
* Protocol-specified alpha fetoprotein range.
* Prothrombin Time/Partial Thromboplastin Time (PT/PTT) values \>10% above laboratory reference range.
* Anti-nuclear antibodies (ANA) \>1:320.

Answer: B