Study of Quadruple Therapy With Eltrombopag for Chronic Hepatitis C

SQUELCH-C is an investigator-initiated, single arm, non-blinded pilot study on the use of
eltrombopag in combination with ribavirin, pegylated-interferon, and boceprevir, for patients
who would not otherwise be treatment candidates because of low platelet counts (less than
75x10^9/L).

Administration of the drugs ribavirin and boceprevir will be standard of care, with one
exception for interferon.

The total drug treatment period for the study patient will range from 32 - 56 weeks,
depending on liver disease stage and viral response. Follow-up will take place at 12 and 24
weeks post treatment to evaluate for sustained viral response. Total study participation may
require 1.5 years.

Inclusion Criteria:

- Male and female patients at least 18 years of age.

- Require a platelet count below 75 x 10^9 /L at time of screening.

- The patients must meet the eligibility criteria for all drugs involved.

- Only genotype 1 (a, b, indeterminate, or mixed).

- Confirmed history of chronic hepatitis C.

- Cirrhotic patients will be included.

- Liver imaging within 1 year to exclude hepatocellular carcinoma (HCC) is required in
patients with cirrhosis.

- Patients without evidence of cirrhosis but meeting platelet criteria will also be
admitted to study.

- Subjects must be able to provide informed consent, comply with drug administration
instructions, and be able to complete each study visit.

- Ability to cover costs of ribavirin, interferon, and boceprevir will also be required.

- Female subjects are eligible if: Non-pregnant, non-childbearing potential, or of
childbearing potential and willing to perform complete abstinence or correctly use a
form of birth control during intercourse [barrier method, intrauterine device,
hormonal therapy, or surgical sterilization in females or male partner]. They must
also be willing to have pregnancy tests performed every 4- weeks until 6 months after
completion of ribavirin.

- Male study participants must agree to use a condom and their female partner must
partake in one of the contraceptive methods discussed above until 6 months after
completion of ribavirin therapy.

Exclusion Criteria:

- A history of chronic infection (i.e., HIV or HBV) or a previous organ transplantation.

- A history of a platelet disorder.

- A poorly controlled underlying medical illness (i.e., diabetes, hypertension, coronary
artery disease, congestive heart failure, etc.).

- Any contraindication to any study drugs as mentioned in their respective prescribing
information.

- Patients with decompensated cirrhosis defined as current evidence for ascites,
encephalopathy, infection or variceal bleeding. All patients should be considered
Child-Pugh Class A.

- Patients with AST/ALT levels ≥ 500 IU/L will be excluded on presumption of another
active liver disease.

- Patients must not be pregnant or nursing.

- The study physician maintains the right to exclude a patient for a medical condition
not listed above or based off laboratory values indicating chronic disease discovered
at screening.

- Patients with eye disease may be excluded from this study if the ophthalmologist does
not recommend treatment.

- Subjects with known hypersensitivity reactions (such as Stevens-Johnson syndrome,
toxic, epidermal necrolysis, and erythema multiforme to ribavirin) to study drugs or
any component of the products.

- Subjects with autoimmune hepatitis, hemoglobinopathies (e.g., thalassemia major,
sickle-cell anemia), creatinine clearance less than 50 mL/min.

- Co-administration of drugs that are highly dependent on CYP3A4/5 for clearance and
CYP3A4/5 inducers (See Table 2 in boceprevir prescribing information).