Back to resultsSafety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
Primary Purpose
Idiopathic Thrombocytopenic Purpura, Thrombocytopenia, Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Romiplostim
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Idiopathic Thrombocytopenic Purpura focused on measuring Immune (Idiopathic) Thrombocytopenic Purpura, Pediatric Immune (Idiopathic) Thrombocytopenic Purpura, Immune Thrombocytopenia
Eligibility Criteria
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
Sites / Locations
- Research Site
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Romiplostim
Placebo
Arm Description
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.
Participants received weekly subcutaneous placebo for 24 weeks.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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?"
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01444417
Brief Title
Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
February 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
Immune (Idiopathic) Thrombocytopenic Purpura, Pediatric Immune (Idiopathic) Thrombocytopenic Purpura, Immune Thrombocytopenia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
62 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Romiplostim
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received weekly subcutaneous placebo for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Romiplostim
Other Intervention Name(s)
AMG 531, Nplate®
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo administered by subcutaneous injection
Primary Outcome Measure Information:
Title
Percentage of Participants With a Durable Platelet Response
Description
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.
Time Frame
Week 18 to week 25
Secondary Outcome Measure Information:
Title
Percentage of Participants With an Overall Platelet Response
Description
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.
Time Frame
Week 2 to week 25
Title
Number of Weeks With Platelet Response
Description
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.
Time Frame
Week 2 to week 25
Title
Percentage of Participants Who Received Rescue Medication During the Treatment Period
Description
Rescue medication is any medication (other than excluded medications) that is intended to increase platelet counts or prevent bleeding.
Time Frame
24 weeks
Title
Total Number of Composite Bleeding Episodes
Description
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.
Time Frame
Week 2 to week 25
Title
Number of Participants With Adverse Events
Description
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?"
Time Frame
From the first dose of study drug until 4 weeks after last dose; 28 weeks.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Research Site
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Research Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Research Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Research Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Research Site
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61615
Country
United States
Facility Name
Research Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Research Site
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Research Site
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Research Site
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70118
Country
United States
Facility Name
Research Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Research Site
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Research Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Research Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89109
Country
United States
Facility Name
Research Site
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Research Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Research Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Research Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Research Site
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States
Facility Name
Research Site
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
Research Site
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Research Site
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Research Site
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8S 4K1
Country
Canada
Facility Name
Research Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Research Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3H 1P3
Country
Canada
Facility Name
Research Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Facility Name
Research Site
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1V 4G2
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
27103127
Citation
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.
Results Reference
derived
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
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