A Long-term Safety Study of Eltrombopag in Pediatric Patients With Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP)

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02201290
• Collaborator: (none)
• Enrollment: 9
• Locations: 3
• Arm: 1
• Actual Duration (Months): 48.5
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was an open-label Phase III extension study to evaluate the long-term safety of eltrombopag in pediatric patients with chronic ITP who previously participated in study TRA115450. This study allowed dosing of eltrombopag at an individualized dose for each subject based upon platelet count. The starting dose was based on the subject's dose at the end of the TRA115450 study. The maximum dose was 75 mg daily.

Condition or Disease	Intervention/Treatment	Phase
Purpura, Thrombocytopenic, Idiopathic	Drug: Eltrombopag Tablets; Drug: Eltrombopag PfOS	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Intervention Model Description: AEs were graded using the common toxicity criteria for adverse events (CTCAE) Version 4.03. If a patient reported more than one AE with the same preferred term (PT), the AE with the greatest severity was presented. If a patient reported more than one AE within the same primary system organ class (SOC), the patient was counted only once with the greatest severity at the SOC level, where applicable. An AE with missing CTCAE grade was included in the 'All grades' column of the summary tables. In AE summaries, the primary SOC was presented alphabetically and the PTs were sorted within the primary SOC in descending frequency.AEs were graded using the common toxicity criteria for adverse events (CTCAE) Version 4.03. If a patient reported more than one AE with the same preferred term (PT), the AE with the greatest severity was presented. If a patient reported more than one AE within the same primary system organ class (SOC), the patient was counted only once with the greatest severity at the SOC level, where applicable. An AE with missing CTCAE grade was included in the 'All grades' column of the summary tables. In AE summaries, the primary SOC was presented alphabetically and the PTs were sorted within the primary SOC in descending frequency.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Extension Study of Eltrombopag in Pediatric Patients With Chronic Immune (Idiopathic) Thrombocytopenia Purpura (ITP)
• Actual Study Start Date: Jun 18, 2013
• Actual Primary Completion Date: Jul 4, 2017
• Actual Study Completion Date: Jul 4, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Eltrombopag Eligible subject will be allocated to 1 of 3 age-defined cohorts. Cohort 1: between 12 and 17 years old, Cohort 2: between 6 and 11 years old, and Cohort 3: between 1 and 5 years old. For Cohorts 1 and 2, eltrombopag tablets will be administered, however, subjects in Cohort 2 may use eltrombopag powder for oral suspension (Eltrombopag PfOS) if they have difficulty swallowing tablets and are receiving a dose of eltrombopag of < 40 mg. For Cohort 3, either eltrombopag tablets or PfOS will be administered.

Drug: Eltrombopag Tablets; Eltrombopag tablets will be white, round film coated tablets containing eltrombopag olamine equivalent to 12.5 mg, 25 mg, 50 mg and 75 mg of eltrombopag. The 12.5 mg tablet will be smaller than the 25 mg, 50 mg and 75 mg tablets. Subjects will receive maximum dose of 75 mg once daily (QD).; Drug: Eltrombopag PfOS; Eltrombopag PfOS is a reddish-brown to yellow powder contained inside an elongated sachet. Each sachet will contain eltrombopag olamine equivalent to 20 mg of eltrombopag per gram of powder. Subjects will receive maximum dose of 75 mg once daily (QD)

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events [Up to week 4 follow up period]

   Frequency of all adverse events (including Ophthalmic events) categorized using CTCAE toxicity grades and clinical laboratory test [ Time Frame: Up to Week 4 Follow-up period ] Clinical laboratory assessments and frequency of all adverse events, categorized using Common Terminology Criteria for Adverse Events (CTCAE) toxicity grades will present safety and tolerability endpoints Serious Adverse Events are below. See All Adverse Events in the following section for specifics No statistical analysis was planned for this primary outcome

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent must be obtained from the subject's guardian and accompanying informed assent from the subject (for children over 6 years old).

• Subjects must be between 1 year and <18 years of age at Day 1.

• Subjects must have enrolled in TRA115450/PETIT2 study.

• Subjects must have completed Part 1 and Part 2 of TRA115450/PETIT2 study.

• Female subjects of child-bearing potential (after menarche) must have a negative pregnancy test within 24 hours of first dose of study treatment; agree and be able to provide a blood or urine specimen for pregnancy testing during the study; agree to use effective contraception during the study and for 28 days following the last dose of study treatment, and not be lactating.

• Male subjects with a female partner of childbearing potential must agree to use effective contraception from 2 weeks prior to administration of the first dose of study treatment until 3 months after the last dose of study treatment.

Exclusion Criteria:

• Subjects with any clinically relevant abnormality, other than ITP, identified on the screening examination or any other medical condition or circumstance, which in the opinion of the investigator makes the subject unsuitable for participation in the study or suggests another primary diagnosis (e.g. Thrombocytopenia is secondary to another disease).

• Any subject considered to be a child in care, defined as one who has been placed under the control or protection of an agency, organization, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. This can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The definition of a child in care does not include a child who is adopted or who has an appointed legal guardian.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Krasnodar		Russian Federation	350007
2	Novartis Investigative Site	Moscow		Russian Federation	117997
3	Novartis Investigative Site	Saint Petersburg		Russian Federation	198205

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Statistical Analysis Plan - Nov 28, 2017
• Study Protocol - Jul 8, 2013

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02201290
• Other Study ID Numbers: 117366; CETB115BRU01; 2017-004082-27
• First Posted: Jul 28, 2014
• Last Update Posted: Jul 5, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Chronic immune thrombocytopenic purpura, ITP, eltrombopag olamine, thrombopoietin receptor agonist, pediatrics
• Additional relevant MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic

Study Results

Participant Flow

Recruitment Details	A total of 9 patients received Eltrombapag treatment during the extension study. Four patients (44.4%) completed the study while 5 patients (55.6%) discontinued from treatment and withdrew from the study.

Arm/Group Title	Eltrombopag
Arm/Group Description	treated participants
Period Title: Overall Study
STARTED	9
COMPLETED	4
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Eltrombopag
Arm/Group Description	all treated participants
Overall Participants	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.7 (3.81)
Sex: Female, Male (Count of Participants)
Female	4 44.4%
Male	5 55.6%
Race/Ethnicity, Customized (Count of Participants)
White - Caucasian	9 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events
Description	Frequency of all adverse events (including Ophthalmic events) categorized using CTCAE toxicity grades and clinical laboratory test [ Time Frame: Up to Week 4 Follow-up period ] Clinical laboratory assessments and frequency of all adverse events, categorized using Common Terminology Criteria for Adverse Events (CTCAE) toxicity grades will present safety and tolerability endpoints Serious Adverse Events are below. See All Adverse Events in the following section for specifics No statistical analysis was planned for this primary outcome
Time Frame	Up to week 4 follow up period

Outcome Measure Data

Analysis Population Description

All treated subjects

Arm/Group Title	Eltrombopag
Arm/Group Description	Adverse events by system organ class and maximum severity for all treated participants
Measure Participants	9
Number of subjects with at least one event	3 33.3%
Scleral haemorrhage	1 11.1%
Autoimmune hepatitis	1 11.1%
Epistaxis	1 11.1%

Adverse Events

Time Frame	up to week 4
Arm/Group Title	Eltrombopag
Arm/Group Description	Eltrombopag was provided to sites by GlaxoSmithKline as tablets or as dry powder for oral suspension (PfOS) sachets
All Cause Mortality
	Eltrombopag
	Affected / at Risk (%)	# Events
Total	0/9 (0%)
Serious Adverse Events
	Eltrombopag
	Affected / at Risk (%)	# Events
Total	3/9 (33.3%)
Eye disorders
Scleral haemorrhage	1/9 (11.1%)
Hepatobiliary disorders
Autoimmune hepatitis	1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/9 (11.1%)
Other (Not Including Serious) Adverse Events
	Eltrombopag
	Affected / at Risk (%)	# Events
Total	6/9 (66.7%)
Infections and infestations
Nasopharyngitis	3/9 (33.3%)
Pharyngitis	1/9 (11.1%)
Tonsillitis	1/9 (11.1%)
Investigations
Blood bilirubin increased	1/9 (11.1%)
Metabolism and nutrition disorders
Iron deficiency	1/9 (11.1%)
Nervous system disorders
Headache	2/9 (22.2%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/9 (11.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.