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

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

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.

Study Overview

• Status: Completed
• 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

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Bussel JB, Buchanan GR, Nugent DJ, Gnarra DJ, Bomgaars LR, Blanchette VS, Wang YM, Nie K, Jun S. A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia. Blood. 2011 Jul 7;118(1):28-36. doi: 10.1182/blood-2010-10-313908. Epub 2011 Apr 18.
• Klaassen RJ, Mathias SD, Buchanan G, Bussel J, Deuson R, Young NL, Collier A, Bomgaars L, Blanchette V. Pilot study of the effect of romiplostim on child health-related quality of life (HRQoL) and parental burden in immune thrombocytopenia (ITP). Pediatr Blood Cancer. 2012 Mar;58(3):395-8. doi: 10.1002/pbc.23312. Epub 2011 Sep 9.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: August 9, 2007
• First Submitted That Met QC Criteria: August 9, 2007
• First Posted (Estimate): August 13, 2007

Study Record Updates

• Last Update Posted (Estimate): July 25, 2014
• Last Update Submitted That Met QC Criteria: July 18, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Immune (Idiopathic) Thrombocytopenic Purpura; Pediatric Idiopathic Thrombocytopenic Purpura
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
• Other Study ID Numbers: 20060195