Safety and Efficacy Study of Romiplostim (AMG 531) to Treat ITP in Pediatric Subjects

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and tolerability of romiplostim (AMG 531) in the treatment of thrombocytopenia in pediatric subjects with chronic ITP. We will also evaluate the efficacy of romiplostim (AMG 531) and characterize the pharmacokinetics of romiplostim (AMG 531). It is anticipated that romiplostim (AMG 531), when given at an effective dose and schedule, will be well tolerated treatment for thrombocytopenia among pediatric subjects with chronic ITP.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-controlled Phase 1/2 Study to Determine the Safety and Efficacy of Romiplostim (AMG 531) in Thrombocytopenic Pediatric Subjects With Chronic Immune (Idiopathic) Thrombocytopenic Purpura

Conditions
-----------------
Idiopathic Thrombocytopenic Purpura, Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP), Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Before any study-specific procedure, the appropriate written informed consent must be obtained. In addition to the written informed consent, the assent of the child from those subjects capable of providing assent must also be obtained if requested by the IRB/IEC. Diagnosis of ITP according to The American Society of Hematology (ASH) Guidelines at least six months prior to screening Age ≥ 12 months and < 18 years at enrollment The mean of two platelet counts taken during the screening period must be ≤ 30 x 10^9/L with no single count >35 x 10^9/L A serum creatinine concentration ≤ 1.5 times the laboratory normal range (for each age category) Adequate liver function; serum bilirubin ≤ 1.5 times the laboratory normal range Hemoglobin >10.0 g/dL Exclusion Criteria: Known history of a 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) Known history of venous or arterial thrombotic or thromboembolic event Known history of congenital thrombocytopenia Known history of malignancy except basal cell carcinoma Known history of hepatitis B, hepatitis C, or HIV Known history of systemic lupus erythematosus, Evans Syndrome, or autoimmune neutropenia Known positive lupus anticoagulant or history of antiphospholipid antibody syndrome Known history of Disseminated Intravascular Coagulation, Hemolytic Uremic Syndrome, or Thrombotic Thrombocytopenic Purpura Currently receiving any treatment for ITP except for corticosteroids IV Ig or anti-D Ig within two weeks prior to the screening visit Rituximab (for any indication) within 14 weeks before the screening visit or anticipated use during the time of the proposed study Splenectomy within eight weeks of the screening visit Received hematopoietic growth factors including IL-11 (oprelvekin) within four weeks before the screening visit Received any alkylating agents within eight weeks before the screening visit or anticipated use during the time of the proposed study Subject is currently enrolled in or has not yet completed at least four weeks since ending other investigational device or drug trial(s), or subject is receiving investigational agent(s) Past or present participation in any study evaluating PEG-rHuMGDF, recombinant human thrombopoietin (rHuTPO), AMG 531, or related platelet product Pregnant (i.e. positive urine pregnancy test) or breast feeding Subject is not using adequate contraceptive precautions, if applicable. Known hypersensitivity to any recombinant E coli-derived product Subject has any kind of disorder that compromises the ability to comply with all study procedures

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: II.<br>5 thrombocytopenic (as defined per protocol) subjects | Drug: Placebo<br>* Starting dose of 1.0 ug/kg. Dose adjustments are made throughout the study based on individual platelet counts.<br>|
| Experimental: I.<br>15 thrombocytopenic (as defined per protocol) subjects | Drug: AMG 531<br>* Starting dose of 1.0 ug/kg. Dose adjustments are made throughout the study based on individual platelet counts.<br>* Other names: romiplostim;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Occurrence of one or more adverse events in the participant during the 12-week treatment period | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weeks With Platelet Count ≥ 50 x 10^9/L | The number of weeks with platelet count ≥ 50 x 10^9/L during the 12 week treatment period. | 12-week treatment period | 
| Bleeding Events (Grade 2 or Higher) | Total number of bleeding events (Grade 2 or higher, i.e., mild to life-threatening, as defined in the protocol) for each participant during Weeks 2-13 (end-of-study visit for non-responders) | 12-week treatment period (Weeks 2 - 13) | 
| Platelet Count ≥ 50 x 10^9/L for Two Consecutive Weeks | Participant incidence of achieving a platelet count ≥50 x 10^9/L for two consecutive weeks during the 12 week treatment period. | 12-week treatment period | 
| Increase in Platelet Count ≥ 20 x 10^9/L Above Baseline for Two Consecutive Weeks | Participant incidence of achieving an increase in platelet count ≥20 x 10^9/L above baseline for two consecutive weeks during the 12 week treatment period. | 12-week treatment period | 
| Requirement for Rescue Therapy (as Defined Per Protocol) | Participant required rescue therapy (as defined per protocol) during the 12 week treatment period. | 12-week treatment period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immune (Idiopathic) Thrombocytopenic Purpura, Pediatric Idiopathic Thrombocytopenic Purpura