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
18 Years
N/A
Both
Hepatitis C Infection, Thrombocytopenia
Trial Information
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
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 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Outcome Measure:
Mean platelet count for actively treated and placebo treated subjects
Outcome Time Frame:
Weeks 6-8
Safety Issue:
No
Principal Investigator
Howard Liebman
Investigator Role:
Principal Investigator
Investigator Affiliation:
USC/Norris Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NC-HEM-07-5
NCT ID:
NCT01153919
Start Date:
March 2010
Completion Date:
April 2015
Related Keywords:
- Hepatitis C Infection
- Thrombocytopenia
- Hepatitis
- Hepatitis A
- Hepatitis C
- Thrombocytopenia
Name | Location |
|---|---|
| USC/Norris Comprehensive Cancer Center | Los Angeles, California 90033-0800 |
