Romiplostim in Treating Hepatitis C-Infected Patients With Thrombocytopenia

April 9, 2017 updated by: University of Southern California

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90033
        • USC/Norris Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of adverse events, including clinically significant changes in laboratory values and the incidence of antibody formation
Time Frame: Weeks 1-24
Weeks 1-24
Number of subjects in each treatment group who achieve a platelet count of greater or equal to 100,000/L
Time Frame: Week 8
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
Time Frame: Weeks 9-24
Weeks 9-24
Changes in plasma HCV viral load during treatment with romiplostim alone
Time Frame: Weeks 1-8
Weeks 1-8
Incidence of sustained viral response achieved during treatment with anti-viral therapy in combination with romiplostim
Time Frame: Weeks 9-24
Weeks 9-24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Southern California

Investigators

  • Principal Investigator: Howard Liebman, University of Southern California

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 30, 2010

Primary Completion (Actual)

July 14, 2014

Study Completion (Anticipated)

July 14, 2018

Study Registration Dates

First Submitted

June 24, 2010

First Submitted That Met QC Criteria

June 28, 2010

First Posted (Estimate)

June 30, 2010

Study Record Updates

Last Update Posted (Actual)

April 11, 2017

Last Update Submitted That Met QC Criteria

April 9, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NC-HEM-07-5
  • NCI-2010-00358

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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