AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of AMG 531 in the treatment of thrombocytopenia in subjects with ITP as measured by the platelet response. This study will also evaluate changes in Patient Reported Outcomes and Health Resource Utilization due to treatment with AMG 531.

Official Title
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A Randomized, Placebo Controlled Study Evaluating the Efficacy and Safety of AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy

Conditions
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Thrombocytopenia, Idiopathic Thrombocytopenic Purpura

Intervention / Treatment
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* Biological: AMG 531
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ITP according to American Society of Hematology (ASH) guidelines (Appendix F) Have completed as least 1 prior treatment for ITP (e.g., prednisone) Subjects greater than 60 years of age must have a documented history of chronic ITP with a bone marrow report to confirm the diagnosis The platelet count (calculated from the mean of the 2 counts taken during the screening and pre-treatment periods) must be: *less than 30 x 10^9/L for those subjects not receiving any ITP therapy, with no count greater than 35 x 10^9/L *less than 50 x 10^9/L for those subjects receiving a constant dose schedule of corticosteroids, azathioprine or danazol with no count greater than 55 x 10^9/L A serum creatinine concentration less than or equal to 2 mg/dl (less than or equal to 176.8 µmol/L) Adequate liver function, as evidenced by a serum bilirubin less than or equal to 1.5 times the laboratory normal range Hemoglobin greater than 11.0 g/dL Written informed consent (see Section 12.1) Exclusion Criteria: Have had a Splenectomy for any reason Any known history of bone marrow stem cell disorder (Any abnormal bone marrow findings other than those typical of ITP must be approved by Amgen before a subject may be enrolled in the study) Any active malignancy. If prior history of cancer other than basal cell carcinoma or cervical carcinoma in situ, no treatment or active disease within 5 years before randomization Documented diagnosis of arterial thrombosis (i.e., stroke, transient ischemic attack or myocardial infarction) in the past year History of venous thrombosis (i.e., deep vein thrombosis, pulmonary embolism) including those subjects who are on ant-coagulation therapy Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure [NYHA greater than class II], uncontrolled hypertension [diastolic greater than 100 mmHg] or cardiac arrhythmia) Have 3 or more of the following predisposing factors for thromboembolic events: diabetes; smoker; using oral contraceptives; on estrogen therapy; known positive for anti-phospholipid antibodies; hypertriglyceridemia; hypercholesteremia (greater than 240 mg/dL); treatment for hypertension Known positive test for human immunodeficiency virus (HIV) infection or hepatitis C virus Currently receiving any treatment for ITP except corticosteroids, azathioprine or danazol administered at a constant dose and schedule IV Ig or anti-D Ig within 2 weeks before the screening visit Rituximab (for any indication) within 14 weeks before the screening visit or anticipated use during the time of the proposed study Received hematopoietic growth factors, including IL-11 (oprelvekin) within 4 weeks before the screening visit Past or present participation in any study evaluating PEG-rHuMGDF, recombinant human thrombopoietin (rHuTPO), AMG 531 or related platelet product Received any aklylating agents within 8 weeks before the screening visit or anticipated use during the time of the proposed study Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication before the screening period - Less than 8 weeks since major surgery Pregnant or breast feeding Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator Known hypersensitivity to any recombinant E coli-derived product Concerns for subject's compliance with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 531<br>Active investigational product | Biological: AMG 531<br>* Weekly subcutaneous dosing based on screening weight and platelet count. Starting dose is at 1mcg/kg up to a maximum dose of 15mcg/kg. AMG 531 is supplied in a 5 mL single use glass vial as a sterile, white, preservative-free, lyophilized powder.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Weekly subcutaneous dosing based on screening weight and platelet count. Starting dose is at 1mcg/kg up to a maximum dose of 15mcg/kg. Placebo is supplied as a lyophilized power in a 5 mL single use glass vial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy of AMG 531 in the treatment of thrombocytopenia in subjects with ITP as measured by durable platelet response during the last 8 weeks of treatment and other platelet response parameters |  | Last 8 weeks of treatments | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the overall safety of AMG 531 |  | Entire duration of the study including the follow up period | 
| To evaluate possible reductions in the dose of concurrent ITP therapies while receiving AMG 531 |  | Entire duration of the study | 
| To evaluate changes in Patient Reported Outcomes (PRO) and Health Resource Utilization (HRU) due to treatment with AMG 531 |  | Entire duration of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immune (idiopathic) thrombocytopenic purpura, pre-splenectomy, ITP, Thrombopenia