Romiplostim in Treating Hepatitis C-Infected Patients With Thrombocytopenia

Thrombocytopenia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01153919
• Other study ID #: NC-HEM-07-5
• Secondary ID: NCI-2010-00358
• Status: Terminated
• Phase: Phase 2
• First received: June 24, 2010
• Last updated: April 9, 2017
• Start date: June 30, 2010
• Est. completion date: July 14, 2018

Study information

• Verified date: April 2017
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: July 14, 2018
• Est. primary completion date: July 14, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Infection
• Thrombocytopenia

Intervention

Biological:
• romiplostim
Given subcutaneously

Drug:
• ribavirin
Given orally

Other:
• placebo
Given subcutaneously

Biological:
• PEG-interferon alfa-2a
Given subcutaneously

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of Southern California

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean platelet count for actively treated and placebo treated subjects		Weeks 6-8
Secondary	Incidence of adverse events, including clinically significant changes in laboratory values and the incidence of antibody formation		Weeks 1-24
Secondary	Number of subjects in each treatment group who achieve a platelet count of greater or equal to 100,000/L		Week 8
Secondary	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		Weeks 9-24
Secondary	Changes in plasma HCV viral load during treatment with romiplostim alone		Weeks 1-8
Secondary	Incidence of sustained viral response achieved during treatment with anti-viral therapy in combination with romiplostim		Weeks 9-24