Romiplostim in Treating Hepatitis C-Infected Patients With Thrombocytopenia

Sponsor
University of Southern California (Other)
Overall Status
Terminated
CT.gov ID
NCT01153919
Collaborator
(none)
27
1
2
96.5
0.3

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: romiplostim
  • Drug: ribavirin
  • Other: placebo
  • Biological: PEG-interferon alfa-2a
  • Other: laboratory biomarker analysis
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. 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:
  1. 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.

  2. To assess the ability of romiplostim to enable subjects to achieve a platelet count sufficient to start antiviral therapy.

  3. 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
27 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 30, 2010
Actual Primary Completion Date :
Jul 14, 2014
Anticipated Study Completion Date :
Jul 14, 2018

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm I

Patients receive romiplostim subcutaneously once weekly for 8 weeks in the absence of disease progression or unacceptable toxicity.

Biological: romiplostim
Given subcutaneously
Other Names:
  • AMG 531
  • Amgen megakaryopoiesis protein 2
  • Nplate
  • Drug: ribavirin
    Given orally
    Other Names:
  • ICN-1229
  • Rebetol
  • RIBA
  • RTCA
  • Viramide
  • Virazole
  • Biological: PEG-interferon alfa-2a
    Given subcutaneously
    Other Names:
  • PEG-IFNA2a
  • PEGASYS
  • pegylated interferon alfa-2a
  • Other: laboratory biomarker analysis
    Correlative studies

    Placebo Comparator: Arm II

    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
    Given orally
    Other Names:
  • ICN-1229
  • Rebetol
  • RIBA
  • RTCA
  • Viramide
  • Virazole
  • Other: placebo
    Given subcutaneously
    Other Names:
  • PLCB
  • Biological: PEG-interferon alfa-2a
    Given subcutaneously
    Other Names:
  • PEG-IFNA2a
  • PEGASYS
  • pegylated interferon alfa-2a
  • Other: laboratory biomarker analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Mean platelet count for actively treated and placebo treated subjects [Weeks 6-8]

    Secondary Outcome Measures

    1. Incidence of adverse events, including clinically significant changes in laboratory values and the incidence of antibody formation [Weeks 1-24]

    2. Number of subjects in each treatment group who achieve a platelet count of greater or equal to 100,000/L [Week 8]

    3. 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]

    4. Changes in plasma HCV viral load during treatment with romiplostim alone [Weeks 1-8]

    5. Incidence of sustained viral response achieved during treatment with anti-viral therapy in combination with romiplostim [Weeks 9-24]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 USC/Norris Comprehensive Cancer Center Los Angeles California United States 90033

    Sponsors and Collaborators

    • University of Southern California

    Investigators

    • Principal Investigator: Howard Liebman, University of Southern California

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Southern California
    ClinicalTrials.gov Identifier:
    NCT01153919
    Other Study ID Numbers:
    • NC-HEM-07-5
    • NCI-2010-00358
    First Posted:
    Jun 30, 2010
    Last Update Posted:
    Apr 11, 2017
    Last Verified:
    Apr 1, 2017

    Study Results

    No Results Posted as of Apr 11, 2017