Eltrombopag vs Standard Front Line Management for Newly Diagnosed Immune Thrombocytopenia (ITP) in Children

A Phase III Study of Eltrombopag vs Standard Front Line Management for Newly Diagnosed Immune Thrombocytopenia in Children

This is an investigator initiated, multicenter, open label, randomized phase 3 study for subjects with newly diagnosed ITP from ages 1 to less than 18 years old.

Study Overview

• Status: Completed
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: Eltrombopag; Drug: Steroids; Drug: IVIG; Drug: Rho(D) Immune Globulin

Detailed Description

This is a prospective, open label, randomized, two-arm, multi-center Phase 3 trial.

Patients with newly diagnosed ITP are randomized 2:1 to receive the experimental treatment, eltrombopag, or investigator's choice of 3 standard therapies. The primary objective is to determine if the proportion of patients with platelet response is significantly greater in patients treated with eltrombopag compared to those treated with standard therapies.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • San Francisco, California, United States, 94158
      • UCSF Benioff Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida College of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Alfac Cancer and Blood Disorder Center: Scottish Rite
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children-Indiana University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospital and Clinics of Minnesota
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Levine Cancer Institute
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97227
      • Randall Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Hasbro Children's Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 14 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: 1- <18 years
• Newly diagnosed ITP (<3 months from diagnosis (first abnormal platelet count), per international working group definition17)
• Platelets <30 x 10^9/L at screening
• Requires pharmacologic treatment from the perspective of the treating clinician.

Need to treat is at the discretion of the investigator, but there should be clinical equipoise about the use of eltrombopag vs standard treatment options (patients should not, in the opinion of the investigator, require concomitant therapy at time of enrollment).

• Treatment options include one of three standard therapies, (IVIg, steroids, or Anti-D). For example, if patient has previously shown no response to IVIg or steroids and is Rh-negative, patient would not be eligible for study.

• Patient population includes both:

  1. Upfront treatment: Patient within 10 days of ITP diagnosis who has not received previous treatment OR

  2. Treatment failure: Patients who have failed standard management (observation or treatment with one or more first-line agents)

     • Failure of observation: no platelet recovery (>30 x 10^9/L) with observation >10 days from diagnosis, with need to treat
     • Poor response to first-line agent (platelets remain <30 x10^9/L)
     • Initial response to first-line agent, but response wanes and platelets fall below 30 x10^9/L
• Family willing and able to return for required lab studies

Exclusion Criteria:

• Severe bleeding: Buchanan Overall Grade 4 or 5 bleeding, or severe bleeding requiring emergent treatment at the discretion of the provider. (e.g., intracranial hemorrhage, pulmonary hemorrhage, bleeding with ongoing need for pRBC transfusion)
• Prior treatment with TPO-RA (eltrombopag or romiplostim)
• Known secondary ITP (due to lupus, CVID, ALPS)
• Known HIV (or history of HIV positivity) or Hepatitis C (screening not required if no clinical suspicion)
• Evans Syndrome: positive direct Coombs with evidence of active hemolysis (elevated lactate dehydrogenase (LDH) or reticulocyte count not attributable to recent treatment or bleeding)
• Any Malignancy
• History of stem cell transplant or solid organ transplant
• aspartate aminotransferase (AST) or ALT >2 x upper limit of normal (ULN)
• Total bilirubin >1.5 × ULN
• Subjects with liver cirrhosis (as determined by the investigator)
• Creatinine >2.5 × ULN
• Known active or uncontrolled infections not responding to appropriate therapy
• On anticoagulation or anti-platelet agents
• Known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator.
• Baseline ophthalmic problems that may potentiate cataract development

• Impaired cardiac function, such as:

  • Known prolonged QTc, with corrected QTc >450 msec
  • Other clinically significant cardio-vascular disease (e.g., uncontrolled hypertension, history of labile hypertension),
  • History of known structural abnormalities (e.g. cardiomyopathy).

• History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following:

  • Recent myocardial infarction (within last 6 months),
  • Uncontrolled congestive heart failure,
  • Unstable angina (within last 6 months),
  • Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker.)
  • Long QT syndrome, family history of idiopathic sudden death, congenital long QT syndrome or additional risk factors for cardiac repolarization abnormality, as determined by the investigator.
• Known immediate or delayed hypersensitivity reaction to eltrombopag or its excipient.

• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. Women of childbearing potential (have achieved menarche) must have a negative serum or urine pregnancy test and agree to use basic methods of contraception (if sexually active) or maintain abstinence for the duration of the study. Basic contraception methods include:

  • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
  • Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject
  • Barrier methods of contraception: Condom or Occlusive cap. For the UK: with spermicidal foam/gel/film/cream/ vaginal suppository
  • Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
• Male patients who are sexually active and do not agree to abstinence or to use a condom during intercourse while taking eltrombopag, and for 7 days after stopping treatment.
• History of alcohol/drug abuse
• Presence of a medical condition that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
• Concurrent participation in an investigational study within 30 days prior to enrollment or within 5-half-lives of the investigational product, whichever is longer. Note: parallel enrollment in a non-therapeutic trial such as disease registry or biology study is permitted.

Other Eligibility Criteria Considerations All patients and/or their parents or legal guardians must sign a written informed consent (and assent when applicable)

• Patients and/or parents who are unable to read at a grade 2 level will be excluded from the patient-reported outcome component of the study, as will non-English speaking patients and/or parents when there is no availability of translated versions in their spoken language . They will not be excluded from all other aspects of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eltrombopag; Patients randomized to eltrombopag will be treated for 12 weeks, with the possibility to continue therapy for up to 1 year depending on response.	Drug: Eltrombopag; Starting dose for eltrombopag will be based on manufacturer recommendations, and drug will be titrated to effect per guidelines.; Children 1 to 5 years: Initial: 25 mg once daily; Children ≥6 years and Adolescents: Initial: 50 mg once daily (25 mg once daily for patients of East-Asian ethnicity [e.g., Chinese, Japanese, Korean, Taiwanese]) Dose should be titrated based on platelet response. Maximum dose: 75 mg once daily.
Active Comparator: Standard first-line therapy; Subjects randomized to the standard therapy arm will receive one of three treatments at the discretion of the treating physician. Patients who previously failed standard management prior to study entry must be treated with a different agent than their original failed agent. e.g. Patient who failed steroids could receive either IVIg or anti-D if randomized to the standard treatment arm. Standard therapy will be administered as commercially available drug. Investigator may choose amongst the following: IVIg: IVIG 1 g/kg x1 (no steroids for pre-medication or adjunctive therapy); Steroids: Prednisone/Prednisolone 4 mg/kg/day (Max 120 mg/day) x 4 days; Rho(D) Immune Globulin: Anti-D globulin 75 mcg/kg x1 (no steroids for pre-medication or adjunctive therapy)	Drug: Steroids; Prednisone/Prednisolone 4mg/kg/day (Max 120 mg/day) x 4 day; Drug: IVIG; IVIG 1 g/kg x1 (no steroids for pre-medication or adjunctive therapy); Drug: Rho(D) Immune Globulin; Anti-D globulin 75 mcg/kg x1 (no steroids for pre-medication or adjunctive therapy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With a Platelet Response	To determine if the percentage of patients with a platelet response is significantly greater in patients with newly diagnosed ITP treated with eltrombopag than those treated with standard first-line treatments	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding Score	Poor bleeding score (binary) at 1, 2, 3, 4 weeks, 12 weeks, and 1 year after study enrollment defined as World Health Organization (WHO) Bleeding Scale ≥ 2 or Modified Buchanan Scale ≥ 3	1 year
Regulatory T-Cells	Absolute change in percentage of CD4+25+Foxp3+ regulatory T cells from baseline at 12 weeks and 1 year	1 year
KIT Scores	Change in parent proxy-reported Kids ITP tool (KIT) overall scores from baseline at 1 week, 4 weeks, 12 weeks, and 1 year after study enrollment	1 year
Hockenberry Fatigue Scale-Parent	Total scale intensity ratings (continuous) from the Hockenberry Fatigue Scale-Parent (FS-P) at 1 week, 4 weeks, 12 weeks, and 1 year	1 year
Cumulative Number of Rescue Therapies Required	The percentage of patients who received rescue therapy in the experimental (eltrombopag) arm vs the comparator (standard therapy) arm during the first 12 weeks of treatment	12 weeks
Platelet Response Among Patients Requiring Rescue Therapy During Weeks 1-2 of Study	Platelet response (binary), defined as ≥ 3 of 4 weeks with platelets >50 x109/L during weeks 6-12 of therapy, but patient required a rescue treatment during weeks 1-2 of study.	12 weeks
Need for Treatment	No further need for treatment (binary) after 12 weeks or 6 months of study	6 months
Treatment Response	Treatment response (binary endpoints) at 1 year defined as: CR is defined as platelet count >/= 150 x 10^9/L; Primary Remission at 1 year is defined as CR at 1 year with no second-line agents required and >/= 3 months after discontinuing most recent platelet active medication; Disease resolution at 1 year is defined as complete response (CR) at 1 year >/= 3 months after discontinuing most recent platelet active medication. May have received a second-line therapy, excluding rituximab or splenectomy.; Disease stability at 1 year is defined as platelets >/= 50 x 10^9/L but <150 x 10^9/L >/= 3 months after discontinuing most recent platelet active medication.	1 year
Number of 2nd Line Therapies	Number of 2nd-line therapies in weeks 13-52	52 weeks
Blood Iron Values	Serum iron, total iron binding capacity (TIBC), transferrin saturation, ferritin, mean corpuscular volume (MCV), and hemoglobin at 12 weeks, 6 months, and 1 year after study enrollment	1 year
Safety Evaluations	Safety evaluations as defined by: Abnormal liver function tests (LFTs): ALT ≥ 3 x upper limit of normal (ULN) in patients with normal baseline ALT ≥ 3 x baseline or ≥ 5 x ULN (whichever is lower) in patients with abnormal baseline ALT ≥ 3 x ULN AND bilirubin ≥ 1.5 x ULN (>35% direct); Incidence of adverse events; Incidence of serious adverse events	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Hospitalizations	Number of hospitalizations	1 year
Time to Response	Time to response (platelets >30x10^9/L, and at least 2-fold increase in the baseline count and absence of bleeding) (IWG definition)	1 year
Platelet-specific Endpoints	Treatment response (platelets >30x10^9/L, and at least 2-fold increase in the baseline count and absence of bleeding) (IWG definition) at 12 weeks	1 year
Time to Platelet Count	Time to platelet count >100x10^9/L and absence of bleeding (IWG definition)	1 year
Treatment Response	Treatment response (platelet count >100x10^9/L and absence of bleeding) (IWG definition) at 12 weeks	1 year
Loss of Treatment Response	Loss of treatment response (platelet count below 30x10^9/L, or less than 2-fold increase in the baseline count or bleeding) (IWG definition) at any time during the study period after achieving response during the first 12 weeks	1 year
Extreme Thrombocytosis	Extreme thrombocytosis (platelets >1 x10^12/L)	1 year
Patient-reported Outcomes Endpoints	Change in child self-reported and parent impact KIT scores from baseline at 1 week, 4 weeks, 12 weeks, and 1 year after study enrollment	1 year
Change in Hockenberry Fatigue	Change in Hockenberry fatigue (FS-C, FS-A, FS-P) scores from baseline at 1 week, 4 weeks, 12 weeks, and 1 year after study enrollment	1 year
Global Change Scale Scores	Global Change Scale scores at 1 week, 4 weeks, 12 weeks, and 1 year after study enrollment	1 year

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: Boston Children's Hospital; University of California, San Francisco
• Investigators: Principal Investigator: Amanda Grimes, MD, Baylor College of Medicine - Texas Children's Hospital

Publications and helpful links

General Publications

• Shimano KA, Grace RF, Despotovic JM, Neufeld EJ, Klaassen RJ, Bennett CM, Ma C, London WB, Neunert C. Phase 3 randomised trial of eltrombopag versus standard first-line pharmacological management for newly diagnosed immune thrombocytopaenia (ITP) in children: study protocol. BMJ Open. 2021 Aug 27;11(8):e044885. doi: 10.1136/bmjopen-2020-044885.

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2019
• Primary Completion (Actual): April 17, 2024
• Study Completion (Actual): February 26, 2025

Study Registration Dates

• First Submitted: April 25, 2019
• First Submitted That Met QC Criteria: May 3, 2019
• First Posted (Actual): May 7, 2019

Study Record Updates

• Last Update Posted (Actual): July 29, 2025
• Last Update Submitted That Met QC Criteria: July 15, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Immune Thrombocytopenia; ITP; Newly Diagnosed Immune Thrombocytopenia; Newly Diagnosed ITP
• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic; Immunologic Factors; Physiological Effects of Drugs; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: H-42131 ICON 3; CETB115JUS33T (Other Identifier: Novartis); ICON 3 (Other Identifier: ICON Consortium)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No