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

Thrombocytopenia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01444417
• Other study ID #: 20080279
• Secondary ID: 2010-018426-39
• Status: Completed
• Phase: Phase 3
• First received: September 29, 2011
• Last updated: February 7, 2017
• Start date: January 2012
• Est. completion date: February 2015

Study information

• Verified date: February 2017
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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.
• Placebo
Matching placebo administered by subcutaneous injection

Locations

Country	Name	City	State
Australia	Research Site	Herston	Queensland
Australia	Research Site	Parkville	Victoria
Australia	Research Site	Randwick	New South Wales
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec City	Quebec
Canada	Research Site	Toronto	Ontario
United States	Research Site	Atlanta	Georgia
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Detroit	Michigan
United States	Research Site	Fort Worth	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Iowa City	Iowa
United States	Research Site	Kansas City	Missouri
United States	Research Site	La Crosse	Wisconsin
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Louisville	Kentucky
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Brunswick	New Jersey
United States	Research Site	New Orleans	Louisiana
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orange	California
United States	Research Site	Peoria	Illinois
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	San Diego	California
United States	Research Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.

External Links

•   AmgenTrials clinical trials website