Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of romiplostim in the treatment of thrombocytopenia in pediatric patients with Immune thrombocytopenia purpura (ITP) as measured by durable platelet response.

Official Title
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A Phase 3 Randomized, Double Blind, Placebo Controlled Study to Determine the Safety and Efficacy of Romiplostim in Thrombocytopenic Pediatric Subjects With Immune Thrombocytopenia (ITP)

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

Intervention / Treatment
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* Drug: Romiplostim
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of primary ITP according to the American Society of Hematology (ASH) guidelines at least 6 months prior to screening, regardless of splenectomy status Subject must be refractory to a prior ITP therapy, having relapsed after at least 1 prior ITP therapy, or ineligible for other ITP therapies; prior therapy includes first-line therapies Age ≥ 1 year and < 18 years at the time of providing informed consent The mean of 2 platelet counts taken during the screening period must be ≤ 30 x 10^9/L with neither count > 35 x 10^9/L A serum creatinine concentration ≤ 1.5 times the laboratory normal range (for each age category) during the screening period Adequate liver function; serum bilirubin ≤ 1.5 times the laboratory normal range during the screening period; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 times the laboratory normal range during the screening period Hemoglobin > 10.0 g/dL during the screening period Subject and/or subject's legally acceptable representative has provided informed consent prior to any study-specific procedure; subject has provided assent, where required 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 active or prior malignancy except adequately treated basal cell carcinoma Known history of congenital thrombocytopenia Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) Known history of H. pylori by urea breath test or stool antigen test within 6 months of enrollment or successfully treated with no evidence of infection Known history of systemic lupus erythematosus, evans syndrome, or autoimmune neutropenia Known history of antiphospholipid antibody syndrome or positive for lupus anticoagulant Known history of disseminated intravascular coagulation, hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura Previous history of venous thromboembolism or thrombotic events Previous use of romiplostim, pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), Eltrombopag, recombinant human thrombopoietin (rHuTPO) or any platelet producing agent Rituximab (for any indication) or 6-mercaptopurine (6-MP) within 14 weeks before the screening visit, or anticipated use during the time of the proposed study Splenectomy within 4 weeks of the screening visit All hematopoietic growth factors including interleukin-11 (IL-11) (oprelvekin) within 4 weeks before the screening visit Alkylating agents within 8 weeks before the screening visit or anticipated use during the time of the proposed study Vaccinations known to decrease platelet counts within 8 weeks before the screening visit Known hypersensitivity to any recombinant E coli-derived product (eg, Infergen, Neupogen, Somatropin, and Actimmune) Other criteria may apply

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romiplostim<br>Participants received once weekly subcutaneous romiplostim for 24 weeks at a starting dose of 1 µg/kg; weekly dose increases continued in increments of 1 µg/kg/week to a maximum dose of 10 µg/kg in an attempt to reach a target platelet count of ≥ 50 x 10^9/L. | Drug: Romiplostim<br>* The starting dose of romiplostim is 1 µg/kg administered weekly by subcutaneous injection. Participants will return to the clinic weekly to provide platelet counts and undergo dose titrations under the supervision of the treating physician. Weekly dose increases will continue in increments of 1 µg/kg up to a maximum dose of 10 µg/kg in an attempt to reach a target platelet count of ≥ 50 x 10^9/L. Dose adjustment will be allowed during the treatment period to maintain a platelet count between ≥ 50 x 10^9/L and ≤ 200 x 10^9/L.<br>* Other names: Nplate®;|
| Placebo Comparator: Placebo<br>Participants received weekly subcutaneous placebo for 24 weeks. | Drug: Placebo<br>* Matching placebo administered by subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Durable Platelet Response | A participant with durable platelet response was defined as achieving at least 6 weekly platelet counts of ≥ 50 x 10^9/L during the last 8 weeks of treatment (platelet counts obtained from week 18 to week 25). If a platelet count from a participant was not available (missing) in a certain week, that week was imputed as non-response for that participant. Platelet counts were not deemed as a positive response for 4 weeks after the administration of rescue medication. | Week 18 to week 25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Overall Platelet Response | Overall platelet response is defined as either a durable platelet response or transient platelet response. Durable platelet response was defined as weekly platelet count ≥ 50 x 10^9/L for 6 or more times during week 18 to week 25 measurements. Participants may not have had a weekly response within 4 weeks after receiving any rescue medication. Transient platelet response was defined as weekly platelet count ≥ 50 x 10^9/L for 4 or more times during week 2 to week 25 measurements but without durable platelet response. Participants may not have had a weekly response within 4 weeks after receiving any rescue medications. | Week 2 to week 25 | 
| Number of Weeks With Platelet Response | Number of weeks with platelet counts ≥ 50 x 10^9/L during week 2 to week 25 measurements. Participants may not have had a weekly response within 4 weeks after receiving any rescue medications. | Week 2 to week 25 | 
| Percentage of Participants Who Received Rescue Medication During the Treatment Period | Rescue medication is any medication (other than excluded medications) that is intended to increase platelet counts or prevent bleeding. | 24 weeks | 
| Total Number of Composite Bleeding Episodes | A composite bleeding episode was defined as clinically significant bleeding events or the use of a rescue medication to prevent a clinical significant bleeding event during weeks 2 through 25 of the treatment period. A clinically significant bleeding event was defined as a Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grade ≥ 2 bleeding event. | Week 2 to week 25 | 
| Number of Participants With Adverse Events | A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: fatal, life threatening (places the subject at immediate risk of death), requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect, and/or other significant medical hazard. Adverse events were graded for severity according to the CTCAE version 3.0 grading scale, where Grade 3 = moderate, Grade 4 = life-threatening and Grade 5 = fatal. Treatment-related adverse events (TRAEs) were those assessed by the investigator as possibly related to study drug. This relationship was determined by a yes or no response to the question: Is there a reasonable possibility that the event may have been caused by study drug? | From the first dose of study drug until 4 weeks after last dose; 28 weeks. | 

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