Clinical trial NCT01153919: Romiplostim in Treating Hepatitis C-Infected Patients With Thrombocytopenia
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hepatitis C Infection
Thrombocytopenia
Lead sponsor: University of Southern California
Sponsor class: OTHER
First posted: 2010-06-30
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Mean platelet count for actively treated and placebo treated subjects
timeFrame: Weeks 6-8
Secondary outcomes:
measure: Incidence of adverse events, including clinically significant changes in laboratory values and the incidence of antibody formation
timeFrame: Weeks 1-24
measure: Number of subjects in each treatment group who achieve a platelet count of greater or equal to 100,000/L
timeFrame: Week 8
measure: 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
timeFrame: Weeks 9-24
measure: Changes in plasma HCV viral load during treatment with romiplostim alone
timeFrame: Weeks 1-8
measure: Incidence of sustained viral response achieved during treatment with anti-viral therapy in combination with romiplostim
timeFrame: Weeks 9-24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of Southern California
name: Howard Liebman
role: PRINCIPAL_INVESTIGATOR
References: