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

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)

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.

Study Overview

• Status: Completed
• Conditions: Thrombocytopenia; Immune Thrombocytopenia; Idiopathic Thrombocytopenic Purpura; Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenic Purpura
• Intervention / Treatment: Drug: Romiplostim; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Research Site
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Research Site
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Research Site
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • Research Site
    • Toronto, Ontario, Canada, M5G 1X8
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H3H 1P3
      • Research Site
    • Montreal, Quebec, Canada, H3T 1C5
      • Research Site
    • Quebec City, Quebec, Canada, G1V 4G2
      • Research Site
• United States
  • California
    • Orange, California, United States, 92868
      • Research Site
    • San Diego, California, United States, 92123
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site
    • Peoria, Illinois, United States, 61615
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Research Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Research Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Research Site
  • New York
    • New York, New York, United States, 10016
      • Research Site
    • New York, New York, United States, 10021
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Research Site
    • Columbus, Ohio, United States, 43205
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15224
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Research Site
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Research Site

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:

• 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

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
Experimental: Romiplostim; 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; 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.; Other Names: Nplate®; AMG 531
Placebo Comparator: Placebo; Participants received weekly subcutaneous placebo for 24 weeks.	Drug: Placebo; Matching placebo administered by subcutaneous injection

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Tarantino MD, Bussel JB, Blanchette VS, Despotovic J, Bennett C, Raj A, Williams B, Beam D, Morales J, Rose MJ, Carpenter N, Nie K, Eisen M. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016 Jul 2;388(10039):45-54. doi: 10.1016/S0140-6736(16)00279-8. Epub 2016 Apr 18.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: September 29, 2011
• First Submitted That Met QC Criteria: September 29, 2011
• First Posted (Estimate): September 30, 2011

Study Record Updates

• Last Update Posted (Estimate): February 9, 2017
• Last Update Submitted That Met QC Criteria: February 7, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Immune Thrombocytopenia; Immune (Idiopathic) Thrombocytopenic Purpura; Pediatric Immune (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: 20080279; 2010-018426-39 (EudraCT Number)