Romiplostim in Treating Hepatitis C-Infected Patients With Thrombocytopenia

NCT ID: NCT01153919

Last Updated: 2017-04-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2018-07-14

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.

Conditions

Hepatitis C Infection; Thrombocytopenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm I

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

Group Type: ACTIVE_COMPARATOR

romiplostim

Intervention Type: BIOLOGICAL

Given subcutaneously

ribavirin

Intervention Type: DRUG

Given orally

PEG-interferon alfa-2a

Intervention Type: BIOLOGICAL

Given subcutaneously

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

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.

Group Type: PLACEBO_COMPARATOR

ribavirin

Intervention Type: DRUG

Given orally

placebo

Intervention Type: OTHER

Given subcutaneously

PEG-interferon alfa-2a

Intervention Type: BIOLOGICAL

Given subcutaneously

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

romiplostim

Given subcutaneously

Intervention Type: BIOLOGICAL

ribavirin

Given orally

Intervention Type: DRUG

placebo

Given subcutaneously

Intervention Type: OTHER

PEG-interferon alfa-2a

Given subcutaneously

Intervention Type: BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

AMG 531; Amgen megakaryopoiesis protein 2; Nplate; ICN-1229; Rebetol; RIBA; RTCA; Viramide; Virazole; PLCB; PEG-IFNA2a; PEGASYS; pegylated interferon alfa-2a

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Southern California

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Howard Liebman

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Locations

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Countries

United States

Other Identifiers

NCI-2010-00358

Identifier Type: -

Identifier Source: secondary_id

NC-HEM-07-5

Identifier Type: -

Identifier Source: org_study_id