NCT01444417 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2017-02-09

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Percentage of Participants With a Durable Platelet Response

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outcome · POSTED

Percentage of Participants With an Overall Platelet Response

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outcome · POSTED

Number of Weeks With Platelet Response

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outcome · POSTED

Percentage of Participants Who Received Rescue Medication During the Treatment Period

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outcome · POSTED

Total Number of Composite Bleeding Episodes

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outcome · POSTED

Number of Participants With Adverse Events

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
maximum Age: 17 Years
minimum Age: 1 Year
sex: ALL
std Ages: CHILD

Treatment arms and interventions

arm Groups

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.
intervention Names
Drug: Romiplostim
label
Romiplostim
type
EXPERIMENTAL
description
Participants received weekly subcutaneous placebo for 24 weeks.
intervention Names
Drug: Placebo
label
Placebo
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Romiplostim
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.
name
Romiplostim
other Names
AMG 531
Nplate®
type
DRUG
arm Group Labels
Placebo
description
Matching placebo administered by subcutaneous injection
name
Placebo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: TRIPLE
who Masked: PARTICIPANT
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 62
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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.
measure
Percentage of Participants With a Durable Platelet Response
time Frame
Week 18 to week 25

secondary Outcomes

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.
measure
Percentage of Participants With an Overall Platelet Response
time Frame
Week 2 to week 25
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.
measure
Number of Weeks With Platelet Response
time Frame
Week 2 to week 25
description
Rescue medication is any medication (other than excluded medications) that is intended to increase platelet counts or prevent bleeding.
measure
Percentage of Participants Who Received Rescue Medication During the Treatment Period
time Frame
24 weeks
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.
measure
Total Number of Composite Bleeding Episodes
time Frame
Week 2 to week 25
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?"
measure
Number of Participants With Adverse Events
time Frame
From the first dose of study drug until 4 weeks after last dose; 28 weeks.

Full 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.

Source references

references

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.
pmid
27103127
type
DERIVED