Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2b, Safety and Efficacy Study of Boceprevir in Patients Coinfected With HIV and Hepatitis C (Protocol No. P05411)
Brief Summary: The primary objective of this trial is to compare the efficacy of boceprevir (SCH 503034) 800 mg three times a day (TID) orally (PO) in combination with peginterferon alfa-2b (PegIFN-2b) 1.5 µg/kg weekly (QW) subcutaneously (SC) plus weight-based dosing (WBD) of ribavirin (RBV) (600 mg/day to 1400 mg/day) PO to therapy with PegIFN-2b + RBV alone in adult participants coinfected with human immunodeficiency virus (HIV) and previously untreated chronic hepatitis C virus (HCV) genotype 1.

Boceprevir is a potent, orally administered, novel serine protease inhibitor, specifically designed to inhibit the HCV nonstructural protein 3 (NS3) protease and, thereby, inhibit viral replication in HCV-infected host cells. The mechanism of inhibition represents a new mechanism of action compared to both interferon alfa and ribavirin. Based on previous experience with PegIFN-2b and RBV in combination with boceprevir in the HCV-monoinfected population, this combination treatment is expected to provide significant benefit to the HIV/HCV coinfected population. Given the high unmet medical need of these participants and the benefit of the addition of boceprevir to PegIFN-2b/RBV, it is important to demonstrate the safety and efficacy of boceprevir in combination with PegIFN-2b/RBV in participants coinfected with HIV/HCV.

This is a randomized, multi-center trial, double-blinded for boceprevir or placebo in combination with open-label PegIFN-2b/RBV in participants coinfected with HIV and previously untreated chronic HCV (genotype 1), to be conducted in conformance with Good Clinical Practice (GCP). This trial consists of two arms, one control arm (Arm 1) and one experimental arm (Arm 2). Participants in the control arm (Arm 1) may receive boceprevir/PegIFN-2b/RBV via a crossover arm.


Options:
A: Inclusion Criteria:

* \>=18 and \<=65 years of age
* Body weight \>=40 and \<=125 kg
* Documented history of HIV infection for greater than 6 months prior to Day 1
* On an optimized anti-retroviral treatment regimen (OTR) with stable HIV disease with CD4 \>=200 cells/µL and HIV-1 RNA viral load \<50 copies/mL
* Documented chronic hepatitis C (CHC) genotype 1 infection (greater than 6 months prior to Day 1)
* Use of acceptable methods of contraception 2 weeks prior to Day 1 and at least 6 months or longer after treatment
* Liver biopsy with histology consistent with CHC and no other etiology

Exclusion Criteria:

* Participants who received prior treatment for hepatitis C other than herbal remedies except those with known hepatotoxicity
* Coinfected with hepatitis B virus (Hepatitis B surface antigen (HBsAg) positive) and/or demonstrating signs and symptoms consistent with concomitant infection
* Evidence of decompensated liver disease
* Participants who have changed their anti-retroviral regimen within the last 3 months prior to Day 1 or had first initiated anti-retroviral therapy within the last 6 months prior to Day 1
* Use of certain HIV medications will not be allowed. Medications will be reviewed by the Investigator
* History of clinically significant opportunistic infections (except oral thrush) within the last year prior to Day 1
* Current evidence of substance abuse within 3 years of the Screening Visit
* History of a clinical diagnosis within the past 6 months of substance abuse prior to Day 1
* Participants receiving opiate agonist substitution therapy but not enrolled in an opiate substitution maintenance program
* History of marijuana use deemed excessive by the Investigator
* Infected with HIV-2
* Use of any HIV protease inhibitor without the coadministration of ritonavir within one month of Day 1 and throughout the period of the trial
* Participants receiving any of the following medication(s) within 2 weeks prior to the Day 1 visit: alfuzosin, antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, and quinidine), ergot derivatives, cisapride, lovastatin, simvastatin, pimozide, triazolam, and orally administered midazolam.

Key Laboratory Exclusion Criteria:

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

  * Hemoglobin \<11 g/dL for females and \<12 g/dL for males
  * Neutrophils \<1500/mm\^3 (blacks/African-Americans: \<1200/mm\^3)
  * Platelets \<100,000/mm\^3
  * Direct bilirubin \>1.5 x ULN (upper limit of normal) of the laboratory reference range. Total bilirubin \>1.6 mg/dL unless history of Gilbert's disease or antiretroviral regimen contains atazanavir. If Gilbert's disease is the proposed etiology, this must be documented in the participant's chart
* Alpha fetoprotein (AFP):

  * AFP \>100 ng/mL OR
  * AFP 50 to 100 ng/mL (requires a liver ultrasound and participants with findings suspicious for hepatocellular carcinoma are excluded)
B: Key Inclusion Criteria:

* Documented chronic genotype 1 or genotype 4 HCV infection
* Naïve to all HCV antiviral treatment(s)
* Agree to IL28B genotyping
* A body mass index \>18 kg/m2 but not exceeding 36 kg/m2
* Liver biopsy obtained within 3 years (36 calendar months) prior to the Day 1 visit, with a fibrosis classification of non-cirrhotic. If no recent (\<36 months) liver biopsy is available, a study qualifying biopsy must be performed prior to Baseline (Day 1)
* All fertile males and females must use two forms of effective contraception between them during treatment and during the 24 weeks after treatment ends
* Otherwise healthy as determined by the medical history, physical examination, ECG findings, and clinical laboratory measurements performed at Screening

Key Exclusion Criteria:

* Positive test at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody
* History of any other clinically significant chronic liver disease
* History of ascites, variceal hemorrhage, hepatic encephalopathy, or conditions consistent with decompensated liver disease
* Positive results on urine screen for drugs of abuse test at Screening (unless used as medical treatment, e.g., with a prescription)
* History of alcohol/drug abuse or dependence within 6 months of the study start (unless participating in a controlled rehabilitation program)
* Screening ECG corrected QT interval value greater than 450 ms and/or clinically significant ECG findings
* A personal or family history of Torsade de Pointes findings
* Pregnant or nursing women
* Males with a female partner who is pregnant
* Abnormal hematological and biochemical parameters as specified in the protocol
* History of major organ transplantation with an existing functional graft
* Thyroid dysfunction not adequately controlled
* Subjects with a history of suicide attempt or hospitalization for depression in the past 5 years and/or any current (within 6 months) severe or poorly controlled psychiatric disorder
* History or current evidence of immunologic disorder; pulmonary, cardiac, or pulmonary disease; seizure disorder; cancer or history of malignancy that in the opinion of the investigator makes the subject unsuitable for the study
* Participation in a clinical study with an investigational drug, biologic, or device within 3 months prior to first dose administration
C: Inclusion Criteria:

* Age \> 18 with chronic genotype 2 or 3 HCV infection
* HCV RNA \> 10,000 IU/mL at screening
* Subjects must be treatment naive or treatment experienced
* Presence or absence of cirrhosis; a liver biopsy may be required
* Healthy according to medical history and physical examination with the exception of HCV diagnosis
* Agree to use two forms of highly effective contraception for the duration of the study and 6 months after the last dose of study medication

Exclusion Criteria:

* Prior use of any other inhibitor of the HCV NS5B Polymerase
* History of any other clinically significant chronic liver disease
* Evidence of or history of decompensated liver disease
* HIV or chronic hepatitis B virus (HBV) infection
* Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers)
* Chronic use of immunosuppressive agents or immunomodulatory agents
* History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study or not be in the best interest of the subject in the opinion of the investigator
D: Inclusion criteria:

1. Chronic hepatitis C infection, diagnosed by positive anti-HCV antibodies and detected HCV RNA at screening in addition to:

   1. positive anti-HCV antibodies or detected HCV RNA at least 6 months prior to screening; or,
   2. liver biopsy consistent with chronic HCV infection.
2. HCV genotype 1 infection confirmed by genotypic testing at screening.
3. Therapy-naïve to interferon, pegylated interferon, ribavirin or any antiviral / immunomodulatory drug for acute or chronic HCV infection.
4. HCV RNA = 1,000 IU/mL at screening
5. Documentation of a liver biopsy within 3 years or fibroscan within 6 months prior to randomization.

   Note: If cirrhosis has been previously demonstrated on a biopsy, then biopsies obtained more than 3 years before randomization need not be repeated. Biopsies may be waived for patients who would be placed at risk from the procedure. Inability to do a liver biopsy in patients at risk for the procedure should not exclude such patients from a trial.
6. Age 18 to 70 years
7. Female patients:

   1. with documented hysterectomy,
   2. who have had both ovaries removed,
   3. with documented tubal ligation,
   4. who are post-menopausal with last menstrual period at least 12 months prior to screening, or
   5. of childbearing potential with a negative serum pregnancy test at screening and Day 1, that, if sexually active, agree to use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of ribavirin in addition to the consistent and correct use of a condom. Patients must agree not to breast-feed at any time from the date of screening until 7 months after the last dose of ribavirin.

   Medically accepted methods of contraception for females in this trial are ethinyl estradiol containing contraceptives, diaphragm with spermicide substance and intra-uterine device.

   Male patients:
   1. who are documented to be sterile, or
   2. who are without pregnant female partner(s) and consistently and correctly use a condom while their female partner(s) (if of child-bearing potential) use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of ribavirin. It is in the responsibility of the male patient to ensure that his partner(s) is not pregnant prior to screening into the study or becomes pregnant during the treatment and the observation phase. Female partners of childbearing potential should perform monthly pregnancy tests from the date of screening until 7 months after the last dose of ribavirin (tests will be provided by the sponsor).
8. Signed informed consent form prior to trial participation

Exclusion criteria:

1. HCV infection of mixed genotype (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening
2. Evidence of acute or chronic liver disease due to causes other than chronic HCV infection. Incidental steatosis diagnosed by biopsy is not an exclusion criterion.
3. HIV co-infection
4. Hepatitis B virus (HBV) infection based on presence of HBs-Ag
5. Active malignancy, or history of malignancy within the last 5 years prior to screening (with an exception of appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix)
6. Active or, history of alcohol or illicit drug abuse other than cannabis within the past 12 months
7. A condition that is defined as one which in the opinion of investigator may put the patient at risk because of participation in this study, may influence the results of this study, or limit the patients ability to participate in this study
8. Usage of any investigational drugs within 30 days prior to screening, or planned usage of an investigational drug during the course of this study.
9. Received concomitant systemic antiviral, hematopoietic growth factor, or immunomodulatory treatment within 30 days prior to randomization. Patients being treated with oral antivirals such as acyclovir, famciclovir or valacyclovir for recurrent herpes simplex infection; or with oseltamivir or zanamivir for influenza A infection, may be screened.
10. Received silymarin (milk thistle), glycyrrhizin, or Sho-saiko-to (SST) within 28 days prior to randomization and throughout the treatment phase of this trial.
11. Known hypersensitivity to any ingredient of the study drugs.
12. Alpha fetoprotein value \> 100 ng/mL at screening; if \> 20 ng/mL and = 100 ng/mL, patients may be included if there is no evidence of liver cancer in an appropriate imaging study (e.g., ultrasound, CT scan, or MRI) within last 6 months prior to randomization (Visit 2).

Other exclusion criteria related to pegylated interferon and/or ribavirin restrictions are not listed here.

Answer: A