Comparative Effectiveness and Tolerability of Boceprevir vs Telaprevir

This is a randomized clinical trial comparing the effectiveness and safety of boceprevir and
telaprevir.

Recruitment of current eligible subjects will occur during their regular appointments at the
Hepatitis C clinic. Eligible patients will have already been cleared for Hepatitis C
treatment through their screening period which is including blood work, liver biopsy, urine
collection/analysis, pregnancy screening and behavioral/mental health screening. On one of
their standard visits to the Hepatitis C clinic, the health care provider(who is also
research staff) or research staff will provide a consent form that the patient may take home
and read more about the study.

On the day of enrollment, which will also be the first day of treatment, health care
providers within the Hepatitis C clinic will describe the study to the patient or refer them
to one of the research for completion of these tasks. The consent form will be explained in
detail at this meeting, and the patient will have the opportunity to ask questions and make
comments about the study.

Study subjects will initially be stratified into 6 groups (1a. treatment naives without
cirrhosis and b. with compensated cirrhosis ; 2a. prior treatment experienced non-responders
without cirrhosis and b. with cirrhosis; 3a. prior treatment experienced relapsers without
cirrhosis and b. with cirrhosis). Patients in each of these groups will be randomized using
random number table and allocation concealment will be achieved by using serially numbered,
opaque, sealed envelopes into one of two study groups. The first group will receive
boceprevir with Peg-IFN and ribavirin as indicated by package insert, and the second group
will receive telaprevir with Peg-IFN and ribavirin as indicated by its package insert. All
other stratified groups will receive protease inhibitor therapy as indicated by the FDA
product labeling.

Safety and effectiveness assessments will be conducted at study entry, PI therapy week 0, 2,
4, 8, 12, 16, 20, 24, 28, 32, 36, 42 and 48, if applicable. Those are SOC visits during the
treatment period and they will include blood tests, complete review of systems, and physical
exams. Patients in all groups will be assessed for sustained viral response (SVR) at 12 and
24 weeks after the last dose of the medication is administered.

Identical to SOC, safety and effectiveness assessments will be determine by health care
providers and the adjudication committee, the latter of which will be unaware of the
treatment arm of the patients. Members of the adjudication committee will be independent of
the treating clinicians, and will be responsible for adjudicating the following outcomes:

- Viral response

- Adverse effects

- Decision regarding treatment discontinuation, based on adverse effect or virological
failure

Inclusion Criteria:

1. At least 18 years of age

2. Have HCV genotype 1 infection and evidence of chronic hepatitis, as confirmed by a
liver biopsy completed within three years prior to enrollment in the study, patients
with cirrhosis will not need to undergo biopsy. Patients with compensated liver
cirrhosis will be eligible. Patients who have previously been treated under standard
of care (Peg-IFN, Ribavrin) and were non-responders, partial responders, or relapsers
will also be eligible.

3. Platelet count >60,000/mm3

4. Absolute neutrophil count > 1000/mm3

5. Hemoglobin >11.0 g/dL for females or >12.0 g/dL for males

6. Serum creatinine
7. Adequately controlled DM

8. Normal or adequately controlled TSH on prescription medication

9. All other clinical laboratory values within normal limits, unless judged not
clinically significant by the investigator

10. Sterile or infertile (defined as vasectomy, tubal ligation, postmenopausal, or
hysterectomy), or willing to use an approved method of double-barrier contraception
(hormonal plus barrier or barrier plus barrier, eg, diaphragm plus condom) from the
time of first dose administration until 6 months after the last dose

11. Capable of understanding instructions, adhering to study schedules and requirements,
and willing to provided informed consent

Exclusion Criteria:

1. Positive HIV or HbsAg serology

2. Severe psychiatric or neuropsychiatric disorders including, but not limited to
uncontrolled severe depression, history of suicidal ideations or suicide attempt(s),
as determinate by SOC psychological evaluation 3 History or clinical manifestations
of significant metabolic, hematological, pulmonary, ischemic or unstable heart
disease, gastrointestinal, neurological, renal, urological, endocrine, ophthalmologic
(including severe retinopathy), or immune mediated disease

4. Chronic hepatic diseases other than hepatitis C 5. Organ or bone marrow transplant 6.
Chronic (greater than 30 days) use of immunosuppressive medications including steroids in
doses equivalent to 10 mg of prednisone or higher, 30 days prior to and anytime during the
course of the study 7. Female patients who are breast-feeding or have a positive pregnancy
test at any time during the study 8. Males whose female partners are pregnant 9. Patients
who have had a malignancy diagnosed and/or treated within the past 3 years, except for
localized squamous or basal cell cancers treated by local excision 10. Patients who have
participated in a clinical trial and have received an investigational drug within 30 days
prior to screening 11. Current alcoholism or drug addiction