Romiplostim in Treating Hepatitis C-Infected Patients With Thrombocytopenia
Primary Purpose
Hepatitis C Infection, Thrombocytopenia
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
romiplostim
ribavirin
placebo
PEG-interferon alfa-2a
laboratory biomarker analysis
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C Infection
Eligibility 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
Sites / Locations
- USC/Norris Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Arm I
Arm II
Arm Description
Patients receive romiplostim subcutaneously once weekly for 8 weeks in the absence of disease progression or unacceptable toxicity.
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.
Outcomes
Primary Outcome Measures
Mean platelet count for actively treated and placebo treated subjects
Secondary Outcome Measures
Incidence of adverse events, including clinically significant changes in laboratory values and the incidence of antibody formation
Number of subjects in each treatment group who achieve a platelet count of greater or equal to 100,000/L
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
Changes in plasma HCV viral load during treatment with romiplostim alone
Incidence of sustained viral response achieved during treatment with anti-viral therapy in combination with romiplostim
Full Information
NCT ID
NCT01153919
First Posted
June 24, 2010
Last Updated
April 9, 2017
Sponsor
University of Southern California
1. Study Identification
Unique Protocol Identification Number
NCT01153919
Brief Title
Romiplostim in Treating Hepatitis C-Infected Patients With Thrombocytopenia
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Terminated
Why Stopped
Approval of several new agents for the treatment of HCV infection would mitigate the future need for interferon HCV treatment
Study Start Date
June 30, 2010 (Actual)
Primary Completion Date
July 14, 2014 (Actual)
Study Completion Date
July 14, 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southern California
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Infection, Thrombocytopenia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I
Arm Type
Active Comparator
Arm Description
Patients receive romiplostim subcutaneously once weekly for 8 weeks in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm II
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
romiplostim
Other Intervention Name(s)
AMG 531, Amgen megakaryopoiesis protein 2, Nplate
Intervention Description
Given subcutaneously
Intervention Type
Drug
Intervention Name(s)
ribavirin
Other Intervention Name(s)
ICN-1229, Rebetol, RIBA, RTCA, Viramide, Virazole
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
placebo
Other Intervention Name(s)
PLCB
Intervention Description
Given subcutaneously
Intervention Type
Biological
Intervention Name(s)
PEG-interferon alfa-2a
Other Intervention Name(s)
PEG-IFNA2a, PEGASYS, pegylated interferon alfa-2a
Intervention Description
Given subcutaneously
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Mean platelet count for actively treated and placebo treated subjects
Time Frame
Weeks 6-8
Secondary Outcome Measure Information:
Title
Incidence of adverse events, including clinically significant changes in laboratory values and the incidence of antibody formation
Time Frame
Weeks 1-24
Title
Number of subjects in each treatment group who achieve a platelet count of greater or equal to 100,000/L
Time Frame
Week 8
Title
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
Time Frame
Weeks 9-24
Title
Changes in plasma HCV viral load during treatment with romiplostim alone
Time Frame
Weeks 1-8
Title
Incidence of sustained viral response achieved during treatment with anti-viral therapy in combination with romiplostim
Time Frame
Weeks 9-24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Howard Liebman
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
USC/Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Romiplostim in Treating Hepatitis C-Infected Patients With Thrombocytopenia
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