Romiplostim in Treating Hepatitis C-Infected Patients With Thrombocytopenia

PRIMARY OBJECTIVES:

I. To assess the platelet count response to administration of weekly romiplostim patients
with HCV infection whose initial platelet count is < 70,000/L.

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of romiplostim the treatment of patients with HCV
infection and thrombocytopenia; including physical symptoms and findings, hematologic, serum
chemistries and liver function tests and adverse events.

II. To assess the ability of romiplostim to enable subjects to achieve a platelet count
sufficient to start antiviral therapy.

III. To assess the ability of romiplostim to maintain platelet counts greater than 50,000/L
while receiving antiviral therapy with pegylated interferon and ribavirin.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive romiplostim subcutaneously once weekly for 8 weeks in the absence of
disease progression or unacceptable toxicity.

Arm II: Patients receive placebo subcutaneously once weekly for 8 weeks. Patients failing to
achieve a platelet count of > 100,000/L cross over to arm I.

Patients achieving a platelet count of > 100,000/L at 8 weeks receive PEG-interferon alfa-2a
subcutaneously once weekly and oral ribavirin once daily. Treatment repeats every 7 days for
24-48 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 and 36 weeks.

Inclusion

- All patients with HCV virus infection documented by detectable plasma HCV antibodies
and RNA who would be excluded by FDA criteria for antiviral treatment with
peginterferon-alpha 2a and ribavirin due to thrombocytopenia (platelets < 70,000/L);
patients cannot have received previous anti-viral therapy with interferon/ribavirin

- Liver biopsy indicating chronic hepatitis within the previous 2 years

- Mean platelet count of < 70,000/L on two repeated measurements in a two week
screening period with no single count >= 75,000/L

- Neutrophil count of >= 1000/mcl

- Hemoglobin >= 11gm/dL and no evidence of active bleeding

- Prothrombin Time (PT) INR < 1.6 seconds

- Albumin >= 2.5 gm/dL

- ALT >= 1.2 and < 10 times upper limit of normal

- No evidence of either ischemic change or cardiac injury on 12-lead electrocardiogram
(EKG)

- Negative pregnancy test and women must be using adequate contraception for at least 2
weeks prior to enrollment and while enrolled in the study

- Signed informed consent within 2 weeks of enrollment and randomization

Exclusion

- Received previous anti-viral therapy with interferon/ribavirin

- Child's Class B and C or acute decompensated liver disease

- Human Immunodeficiency Virus (HIV) infection or co-infected with hepatitis B virus

- Any untreated active infection

- Active malignancy, known primary bone marrow disorder (myelodysplasia,
myeloproliferative disease, etc.), or history of blood or bone marrow
transplantation; patients with documented hemoglobinopathies

- Active vasculitis associated with cryoglobulinemia as manifested by either renal
disease or dermatologic findings

- Positive pregnancy test or men with pregnant partners

- Creatinine and BUN of greater than twice (2x) the upper limits of normal

- History of venous or arterial thrombosis, myocardial infarction or thrombotic stroke

- Patients who in the investigators opinion will fail to be compliant or have other
contraindication to treatment on this study

- Other inherited or acquired liver disease

- Previous solid organ transplant

- Known hypersensitivity to E. coli derived recombinant proteins

- Active rheumatologic disease including Systemic Lupus Erythematosis

- Known history of Disseminated Intravascular Coagulation, Hemolytic Uremic Syndrome,
or Thrombotic Thrombocytopenic Purpura