Trial Outcomes & Findings for Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients (NCT NCT01444417)

Last Updated: 2017-02-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

62 participants

Primary outcome timeframe

Week 18 to week 25

Results posted on

2017-02-09

Participant Flow

This study was conducted at 27 centers in the United States, Canada, and Australia. Participants were enrolled from 24 January 2012 to 03 September 2014.

Participants who met eligibility criteria were enrolled and stratified by the following 3 age categories: ≥ 1 to \< 6 years; 6 to \< 12 years; and 12 to \< 18 years.

Participant milestones

Participant milestones
Measure	Placebo Participants received weekly subcutaneous placebo for 24 weeks.	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.
Overall Study STARTED	20	42
Overall Study Received Treatment	19	42
Overall Study COMPLETED	18	41
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received weekly subcutaneous placebo for 24 weeks.	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.
Overall Study Ineligibility Determined	0	1
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=20 Participants Participants received weekly subcutaneous placebo for 24 weeks.	Romiplostim n=42 Participants 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.	Total n=62 Participants Total of all reporting groups
Age, Continuous	9.4 years STANDARD_DEVIATION 4.7 • n=5 Participants	9.7 years STANDARD_DEVIATION 4.1 • n=7 Participants	9.6 years STANDARD_DEVIATION 4.3 • n=5 Participants
Age, Customized ≥ 1 - < 6 years	4 participants n=5 Participants	8 participants n=7 Participants	12 participants n=5 Participants
Age, Customized ≥ 6 - < 12 years	9 participants n=5 Participants	18 participants n=7 Participants	27 participants n=5 Participants
Age, Customized ≥ 12 - < 18 years	7 participants n=5 Participants	16 participants n=7 Participants	23 participants n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	24 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	18 Participants n=7 Participants	27 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants
Race/Ethnicity, Customized Multiple	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized White	15 participants n=5 Participants	26 participants n=7 Participants	41 participants n=5 Participants
Platelets	19.9 10^9/L STANDARD_DEVIATION 19.3 • n=5 Participants	17.5 10^9/L STANDARD_DEVIATION 10.7 • n=7 Participants	18.3 10^9/L STANDARD_DEVIATION 13.9 • n=5 Participants

PRIMARY outcome

Timeframe: Week 18 to week 25

Population: Efficacy analysis set (all randomized participants)

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received weekly subcutaneous placebo for 24 weeks.	Romiplostim n=42 Participants 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.
Percentage of Participants With a Durable Platelet Response	10.0 percentage of participants Interval 1.2 to 31.7	52.4 percentage of participants Interval 36.4 to 68.0

SECONDARY outcome

Timeframe: Week 2 to week 25

Population: Efficacy analysis set

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.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received weekly subcutaneous placebo for 24 weeks.	Romiplostim n=42 Participants 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.
Percentage of Participants With an Overall Platelet Response	20.0 percentage of participants Interval 5.7 to 43.7	71.4 percentage of participants Interval 55.4 to 84.3

SECONDARY outcome

Timeframe: Week 2 to week 25

Population: Efficacy analysis set

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.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received weekly subcutaneous placebo for 24 weeks.	Romiplostim n=42 Participants 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.
Number of Weeks With Platelet Response	1.0 weeks Interval 0.0 to 22.0	12.0 weeks Interval 0.0 to 24.0

SECONDARY outcome

Timeframe: 24 weeks

Population: Efficacy analysis set

Rescue medication is any medication (other than excluded medications) that is intended to increase platelet counts or prevent bleeding.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received weekly subcutaneous placebo for 24 weeks.	Romiplostim n=42 Participants 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.
Percentage of Participants Who Received Rescue Medication During the Treatment Period	45.0 percentage of participants Interval 23.1 to 68.5	40.5 percentage of participants Interval 25.6 to 56.7

SECONDARY outcome

Timeframe: Week 2 to week 25

Population: Efficacy analysis set

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.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received weekly subcutaneous placebo for 24 weeks.	Romiplostim n=42 Participants 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.
Total Number of Composite Bleeding Episodes	4.0 bleeding episodes Standard Deviation 6.9	1.9 bleeding episodes Standard Deviation 4.2

SECONDARY outcome

Timeframe: From the first dose of study drug until 4 weeks after last dose; 28 weeks.

Population: Safety analysis set (all participants who received at least one dose of study drug)

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?"

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received weekly subcutaneous placebo for 24 weeks.	Romiplostim n=42 Participants 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.
Number of Participants With Adverse Events Any adverse event (AE)	19 participants	41 participants
Number of Participants With Adverse Events Serious adverse events (SAE)	1 participants	10 participants
Number of Participants With Adverse Events AE leading to discontinuation of study drug	0 participants	0 participants
Number of Participants With Adverse Events AE leading to discontinuation from study	0 participants	0 participants
Number of Participants With Adverse Events Grade 3 AE	3 participants	6 participants
Number of Participants With Adverse Events Grade 4 AE	1 participants	2 participants
Number of Participants With Adverse Events Grade 5 AE	0 participants	0 participants
Number of Participants With Adverse Events Treatment-related adverse events (TRAE)	5 participants	11 participants
Number of Participants With Adverse Events Treatment-related serious adverse events	0 participants	1 participants
Number of Participants With Adverse Events TRAE leading to discontinuation of study drug	0 participants	0 participants
Number of Participants With Adverse Events TRAE leading to discontinuation from study	0 participants	0 participants
Number of Participants With Adverse Events TRAE Grade 3	0 participants	1 participants
Number of Participants With Adverse Events TRAE Grade 4	0 participants	0 participants
Number of Participants With Adverse Events TRAE Grade 5	0 participants	0 participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Romiplostim

Serious events: 10 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=19 participants at risk Participants received weekly subcutaneous placebo for 24 weeks.	Romiplostim n=42 participants at risk 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.
Nervous system disorders Petit Mal Epilepsy	0.00% 0/19 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.4% 1/42 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Haematuria	5.3% 1/19 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/42 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Nephrotic Syndrome	0.00% 0/19 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.4% 1/42 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/19 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.8% 2/42 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/19 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.4% 1/42 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/19 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.4% 1/42 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	0.00% 0/19 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.4% 1/42 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	0.00% 0/19 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.4% 1/42 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pyrexia	0.00% 0/19 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.4% 1/42 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Bronchiolitis	0.00% 0/19 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.4% 1/42 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Urinary Tract Infection	0.00% 0/19 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.4% 1/42 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Animal Bite	5.3% 1/19 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/42 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Contusion	0.00% 0/19 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.4% 1/42 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	0.00% 0/19 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.8% 2/42 • From the first dose of study drug until 4 weeks after last dose; 28 weeks. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER