Approval of several new agents for the treatment of HCV infection would mitigate the future need for interferon HCV treatment

RATIONALE: Romiplostim may cause the body to make platelets.

PURPOSE: This randomized phase II trial is studying how well romiplostim works 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