Romiplostim in Treating Hepatitis C-Infected Patients With Thrombocytopenia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Double-Blind, Placebo-controlled Phase II Study to Assess the Efficacy and Safety of Romiplostim, Administered Once Weekly to Thrombocytopenic Hepatitis C (HCV) Infected Subjects Who Are Not Candidates for Antiviral Treatment With Pegylated Interferon and Ribavirin Due to Persistent Thrombocytopenia

Conditions
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Hepatitis C Infection, Thrombocytopenia

Intervention / Treatment
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* Biological: romiplostim
* Drug: ribavirin
* Other: placebo
* Biological: PEG-interferon alfa-2a
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients receive romiplostim subcutaneously once weekly for 8 weeks in the absence of disease progression or unacceptable toxicity. | Biological: romiplostim<br>* Given subcutaneously<br>* Other names: Nplate;Drug: ribavirin<br>* Given orally<br>* Other names: Virazole;Biological: PEG-interferon alfa-2a<br>* Given subcutaneously<br>* Other names: pegylated interferon alfa-2a;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Placebo Comparator: Arm II<br>Patients receive placebo subcutaneously once weekly for 8 weeks. Patients failing to achieve a platelet count of &gt; 100,000/L cross over to arm I. | Drug: ribavirin<br>* Given orally<br>* Other names: Virazole;Other: placebo<br>* Given subcutaneously<br>* Other names: PLCB;Biological: PEG-interferon alfa-2a<br>* Given subcutaneously<br>* Other names: pegylated interferon alfa-2a;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean platelet count for actively treated and placebo treated subjects |  | Weeks 6-8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events, including clinically significant changes in laboratory values and the incidence of antibody formation |  | Weeks 1-24 | 
| Number of subjects in each treatment group who achieve a platelet count of greater or equal to 100,000/L |  | Week 8 | 
| Number of patients originally receiving active treatment who maintain a platelet count &gt; 50,000/L while receiving anti-viral therapy with pegylated interferon and ribavirin |  | Weeks 9-24 | 
| Changes in plasma HCV viral load during treatment with romiplostim alone |  | Weeks 1-8 | 
| Incidence of sustained viral response achieved during treatment with anti-viral therapy in combination with romiplostim |  | Weeks 9-24 |