Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body.

NCT ID: NCT01520909

Last Updated: 2015-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2014-01-31

Brief Summary

The purpose of this study is to investigate the efficacy, safety and tolerability of eltrombopag in children with previously treated chronic immune thrombocytopenia who are between 1 and 17 years of age. This is a 2 part study. In part 1, patients will be randomized to receive either eltrombopag or placebo for 13 weeks. All patients who complete part 1 will enter part 2. In part 2, all patients will receive 24 weeks of eltrombopag.

Detailed Description

This is a two part, double-blind, randomized, placebo-controlled and open-label Phase III study to investigate the efficacy, safety and tolerability of eltrombopag in pediatric patients with previously treated chronic ITP. In Part 1, patients will be randomized to receive eltrombopag or placebo in a 13-week double-blind, placebo-controlled treatment period. After completing Part 1, patients will begin Part 2, in which they will receive eltrombopag in an open-label manner during a 24-week treatment period.

Conditions

Idiopathic Thrombocytopenic Purpura

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Eltrombopag plus standard of care

Part 1, double-blind treatment group

Group Type: EXPERIMENTAL

Eltrombopag

Intervention Type: DRUG

Thrombopoietin receptor agonist

Placebo plus standard of care

Part 1, double-blind treatment group

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo with no active pharmaceutical ingredient

Eltrombopag plus standard of care (Part 2 open-label)

Part 2, open-label

Group Type: EXPERIMENTAL

Eltrombopag

Intervention Type: DRUG

Thrombopoietin receptor agonist

Interventions

Eltrombopag

Thrombopoietin receptor agonist

Intervention Type: DRUG

Placebo

Placebo with no active pharmaceutical ingredient

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Written informed consent must be obtained from the patient's guardian and accompanying informed assent from the patient (for children over 6 years old)
• Patients must be between 1 year and <18 years of age at Day 1
• Patients will have a confirmed diagnosis of chronic ITP for at least 1 year, at screening, according to the guidelines published in the International Working Group Report
• A peripheral blood smear or bone marrow examination will support the diagnosis of ITP with no evidence of other causes of thrombocytopenia.
• Patients must be refractory or have relapsed after at least one prior ITP therapy, or patients must be unable, for a medical reason, to continue other ITP treatments.
• Patients must have a Day 1 (or within 48 hours prior) platelet count <30 Gi/L.
• Previous therapy for ITP with immunoglobulins (IVIg and anti-D) must have been completed at least 2 weeks prior to Day 1, or these therapies must have been completed at least 1 week prior to Day 1 and have been clearly ineffective.
• Previous treatment for ITP with splenectomy, rituximab and cyclophosphamide must have been completed at least 4 weeks prior to Day 1.
• Patients treated with concomitant ITP medication (e.g. corticosteroids or azathioprine) must be receiving a dose that has been stable for at least 4 weeks prior to Day 1.
• Patients must have a complete blood count (CBC) not suggestive of another hematological disorder.
• Patients must have the following laboratory results:
• prothrombin time international normalized ratio (INR) and activated partial thromboplastin time (aPTT) within 80 to 120% of the normal range.
• clinical chemistries that do NOT exceed the upper limit of normal reference range by more than 20% for the following: creatinine, ALT, AST, total bilirubin, and alkaline phosphatase.
• total albumin that is not below the lower limit of normal by more than 10%.
• Female patients 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 patients 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.
• In France, a patient will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria

• Patients 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 patient unsuitable for participation in the study or suggests another primary diagnosis (e.g. Thrombocytopenia is secondary to another disease).
• Patients with concurrent or past malignant disease, including myeloproliferative disorder.
• Patients expected not to be suitable for continuation of their current therapy for at least 13 additional weeks.
• Patients with a history of platelet agglutination abnormality that prevents reliable measurement of platelet counts.
• Patients with a diagnosis of secondary immune thrombocytopenia, including those with laboratory or clinical evidence of HIV infection, anti-phospholipid antibody syndrome, chronic hepatitis B infection, hepatitis c virus infection, or any evidence of active hepatitis at the time of subject screening.
• Patients with Evans syndrome (autoimmune thrombocytopenia and autoimmune hemolysis).
• Patients with known inherited thrombocytopenia (e.g. MYH9 disorders).
• Patients treated with any medication that affects platelet function (including but not limited to aspirin, clopidogrel and/or NSAIDS) or anti-coagulants for >3 consecutive days within 2 weeks of Day 1.
• Patients who have received treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding Day 1.
• Patients who have previously received eltrombopag or any other thrombopoietin receptor agonist.
• Any patient 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.
• Patients who have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or excipients that contraindicates their participation.
• Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with the patient's safety or compliance to the study procedures.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

St. Petersburg, Florida, United States

GSK Investigational Site

Brooklyn, New York, United States

GSK Investigational Site

Salt Lake City, Utah, United States

GSK Investigational Site

Capital Federal, Buenos Aires, Argentina

GSK Investigational Site

Brno, , Czechia

GSK Investigational Site

Olomouc, , Czechia

GSK Investigational Site

Ostrava, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, Germany

GSK Investigational Site

Mainz, Rhineland-Palatinate, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Pokfulam, , Hong Kong

GSK Investigational Site

Shatin, , Hong Kong

GSK Investigational Site

Beersheba, , Israel

GSK Investigational Site

Haifa, , Israel

GSK Investigational Site

Petah Tikva, , Israel

GSK Investigational Site

Ramat Gan, , Israel

GSK Investigational Site

Rehovot, , Israel

GSK Investigational Site

Tel Aviv, , Israel

GSK Investigational Site

Bologna, Emilia-Romagna, Italy

GSK Investigational Site

Rome, Lazio, Italy

GSK Investigational Site

Monza, Lombardy, Italy

GSK Investigational Site

Turin, Piedmont, Italy

GSK Investigational Site

Bydgoszcz, , Poland

GSK Investigational Site

Gdansk, , Poland

GSK Investigational Site

Lodz, , Poland

GSK Investigational Site

Lublin, , Poland

GSK Investigational Site

Krasnodar, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Málaga, , Spain

GSK Investigational Site

Murcia (El Palmar), , Spain

GSK Investigational Site

Pamplona, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Tainan City, , Taiwan

GSK Investigational Site

Taoyuan District, , Taiwan

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Khon Kaen, , Thailand

GSK Investigational Site

Songkhla, , Thailand

GSK Investigational Site

Birmingham, , United Kingdom

GSK Investigational Site

Cardiff, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Manchester, , United Kingdom

GSK Investigational Site

Romford, , United Kingdom

GSK Investigational Site

Sheffield, , United Kingdom

Countries

United States; Argentina; Czechia; Germany; Hong Kong; Israel; Italy; Poland; Russia; Spain; Taiwan; Thailand; United Kingdom

References

Wire MB, Li X, Zhang J, Sallas W, Aslanis V, Ouatas T. Modeling and Simulation Support Eltrombopag Dosing in Pediatric Patients With Immune Thrombocytopenia. Clin Pharmacol Ther. 2018 Dec;104(6):1199-1207. doi: 10.1002/cpt.1066. Epub 2018 Apr 17.

Reference Type: DERIVED

PMID: 29536526 (View on PubMed)

Grainger JD, Locatelli F, Chotsampancharoen T, Donyush E, Pongtanakul B, Komvilaisak P, Sosothikul D, Drelichman G, Sirachainan N, Holzhauer S, Lebedev V, Lemons R, Pospisilova D, Ramenghi U, Bussel JB, Bakshi KK, Iyengar M, Chan GW, Chagin KD, Theodore D, Marcello LM, Bailey CK. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2015 Oct 24;386(10004):1649-58. doi: 10.1016/S0140-6736(15)61107-2. Epub 2015 Jul 28.

Reference Type: DERIVED

PMID: 26231455 (View on PubMed)

Other Identifiers

2011-002184-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

115450

Identifier Type: -

Identifier Source: org_study_id