P3 Study to Evaluate Efficacy and Safety of AMG 531 in Thrombocytopenic Japanese Subjects With Immune (Idiopathic) Thrombocytopenic Purpura

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of AMG 531 compared with placebo in thrombocytopenic Japanese subjects with immune (idiopathic) thrombocytopenic purpura (ITP) .

Official Title
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A Randomized, Double Blind, Placebo Controlled Phase 3 Study Evaluating the Efficacy and Safety of AMG 531 in Thrombocytopenic Japanese Subjects With Immune (Idiopathic) Thrombocytopenic Purpura

Conditions
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Idiopathic Thrombocytopenic Purpura

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese patients with diagnosis of ITP according to the diagnostic criteria proposed by Research Committee for Idiopathic Hematopoietic Disorders of the Ministry of Health, Labour and Welfare [MHLW] (revised in 1990) at least 6 months before the first screening visit The mean of the 3 scheduled platelet counts taken at the scheduled visits during the screening period must be ≤ 30 x 10^9/L, with no individual count > 35 x 10^9/L Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 Subjects must be ≥ 20 years of age at the time of obtaining the informed consent Have received at least 1 prior treatment for ITP If known Helicobacter pylori positive, having completed one course of Helicobacter pylori eradication therapy at least 12 weeks before the first screening visit A hemoglobin value taken at scheduled visit during the screening period must be ≥ 10 g/dL A serum creatinine concentration taken at scheduled visit during the screening period must be ≤ 2 mg/dL Adequate liver function, as evidenced by a total bilirubin taken at scheduled visit during the screening period ≤ 1.5 times of the upper limit of the normal range (except for patients with a confirmed diagnosis of Gilbert's Disease) or an alanine aminotransferase and aspartate aminotransferase taken at the screening visit ≤ 3 times of the upper limit of the normal range Exclusion Criteria: Any known history of bone marrow stem cell disorder. Any abnormal bone marrow findings other than those typical of ITP. 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 the first screening visit. Documented diagnosis of arterial thrombosis (eg, stroke, transient ischemic attack, or myocardial infarction); history of venous thrombosis (eg, deep vein thrombosis, pulmonary embolism) and receiving anticoagulation therapy at the first screening visit. Documented diagnosis of anti phospholipid antibody syndrome Currently receiving any treatment for ITP except oral corticosteroids, azathioprine and/or danazol administered at a constant dose and schedule from at least 4 weeks prior to the first screening visit Received intravenous immunoglobulin, anti D immunoglobulin, or any drug administered to increase platelet counts (eg, immunosuppressants except azathioprine) within 2 weeks before the first screening visit Have had a splenectomy for any reason within 12 weeks before the first screening visit Past or present participation in any study evaluating pegacaristim (polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor, KRN9000), Eltrombopag (SB 497115), recombinant human thrombopoietin, AMG 531, or other Mpl stimulation product Received hematopoietic growth factors (eg, granulocyte colony stimulating factor, macrophage colony stimulating factor, erythropoietin, interleukin 11) for any reason within 4 weeks before the first screening visit Received any anti malignancy agents (eg, cyclophosphamide, 6 mercaptopurine, vincristine, vinblastine, Interferon alfa) for any reason within 8 weeks before the first screening visit Received any monoclonal antibody drugs (eg, rituximab) for any reason within 14 weeks before the first screening visit Less than 4 weeks since receipt of any therapeutic drug or device that is not MHLW approved for any indication before the first screening visit Pregnant or breast feeding Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator Known severe drug hypersensitivity Concerns for subject's compliance with the protocol

Ages Eligible for Study
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Minimum Age: 20 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: AMG 531<br>Double blinded placebo-controlled study | Drug: AMG 531<br>* Subcutaneously administered, once a week, for 12 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Subcutaneously administered, once a week, for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weeks With Weekly Platelet Response | Number of weeks with weekly platelet response. A weekly platelet response is defined as a platelet count of ≥ 50 x 10^9/L on a weekly scheduled dose day from week 2 to week 13. | 12 weeks (Weeks 2 - 13) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increased Platelet Count From Baseline of at Least 20 x 10^9/L | An increase in platelet count of at least 20 x 10^9/L from baseline within the participant during the treatment period. Increase was calculated as the maximum observed platelet count during the treatment period minus the baseline platelet count. | Baseline, 12 weeks (Weeks 2 - 13) | 
| Change From Baseline in Mean of Last 4 Weekly Platelet Counts | Change from baseline in the mean of the last 4 weekly platelet counts from week 2 to week 13. | 12 weeks (Weeks 2 - 13) | 
| Weeks With Platelet Count Between 50 and 200 | Number of weeks with platelet count between 50 x 10^9/L and 200 x 10^9/L inclusive during week 2 to week 13. | 12 weeks (Weeks 2 - 13) | 
| Rescue Medication(s) | Requirement for rescue medication(s) during treatment by the participant | 12 weeks (Weeks 2 - 13) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMG 531, Idiopathic Thrombocytopenic Purpura, ITP, Thrombocytopenia, Japan, Placebo controlled, Phase 3