Hepatitis C Infection, Thrombocytopenia
Conditions
Brief summary
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
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.
Interventions
OTHERlaboratory biomarker analysis
Correlative studies
BIOLOGICALromiplostim
Given subcutaneously
DRUGribavirin
Given orally
OTHERplacebo
Given subcutaneously
BIOLOGICALPEG-interferon alfa-2a
Given subcutaneously
Sponsors
University of Southern California
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean platelet count for actively treated and placebo treated subjects | Weeks 6-8 |
Secondary
| Measure | 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 > 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 |
Countries
United States
Outcome results
None listed