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Romiplostim in Treating Hepatitis C-Infected Patients With Thrombocytopenia

This study is currently recruiting participants.
Verified November 2012 by USC/Norris Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
USC/Norris Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01153919
First received: June 24, 2010
Last updated: November 29, 2012
Last verified: November 2012
History of Changes
  Purpose

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 Intervention Phase
Hepatitis C Infection
Thrombocytopenia
 Biological: romiplostim
Drug: ribavirin
Other: placebo
Biological: PEG-interferon alfa-2a
Other: laboratory biomarker analysis
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by USC/Norris Comprehensive Cancer Center:

Primary Outcome Measures:
  • Mean platelet count for actively treated and placebo treated subjects [ Time Frame: Weeks 6-8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of adverse events, including clinically significant changes in laboratory values and the incidence of antibody formation [ Time Frame: Weeks 1-24 ] [ Designated as safety issue: Yes ]
  • Number of subjects in each treatment group who achieve a platelet count of greater or equal to 100,000/L [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Changes in plasma HCV viral load during treatment with romiplostim alone [ Time Frame: Weeks 1-8 ] [ Designated as safety issue: No ]
  • Incidence of sustained viral response achieved during treatment with anti-viral therapy in combination with romiplostim [ Time Frame: Weeks 9-24 ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: March 2010
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 > 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 Name: PLCB
Biological: PEG-interferon alfa-2a
Given subcutaneously
Other Names:
  • PEG-IFNA2a
  • PEGASYS
  • pegylated interferon alfa-2a
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01153919

Contacts
Contact: Laurie Hornor, RN 323-865-3978 Laurie.Hornor@med.usc.edu

Locations
United States, California
USC/Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Laurie A. Hornor, RN     323-865-3978     Laurie.Hornor@med.usc.edu    
Contact: Zeno Ashai     323-865-0463     zeno.ashai@med.usc.edu    
Principal Investigator: Howard A. Liebman            
Sponsors and Collaborators
USC/Norris Comprehensive Cancer Center
Investigators
Principal Investigator: Howard Liebman USC/Norris Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: USC/Norris Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01153919     History of Changes
Other Study ID Numbers: NC-HEM-07-5, NCI-2010-00358
Study First Received: June 24, 2010
Last Updated: November 29, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Thrombocytopenia
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Blood Platelet Disorders
Hematologic Diseases
Interferon-alpha
 Interferon Alfa-2a
Interferons
Ribavirin
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 23, 2013