Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic Idiopathic Thrombocytopenic Purpura (ITP)

NCT00908037 | Completed Phase 2 Results DMC

• 1 other identifier: 108062
• Study Type: interventional
• Target: 82
• Locations: 6 countries
• Sites: 33

Brief Summary

Phase II, multi-center, 3 part, staggered cohort, open-label and double blind, randomized, placebo controlled study involving 3 age-determined cohorts (Cohort 1: between 12 and 17 years old; Cohort 2: between 6 and 11 years old; Cohort 3: between 1 and 5 years old). Daily dosing with eltrombopag will begin with 5 patients in the oldest age cohort in an open label fashion, and a review of safety, pharmacokinetic and platelet count data will be performed regularly. If no safety concerns are identified after 12 weeks, 18 additional patients will be randomised to placebo or eltrombopag (2:1 randomisation). After 7 weeks of randomized treatment, all patients will receive eltrombopag in an open label fashion. The total duration of treatment with eltrombopag will be 24 weeks. If at the time of the aforementioned 12 week review of the first 5 patients no safety issues are identified, dosing will begin in the next lower age cohort with an initial group of 5 patients. The same procedure will be followed in terms of safety review and subsequent enrolment and randomisation of the additional patients. Initiation of the younger age cohort will take place once data from the previous has been evaluated. Doses will be adjusted according to platelet counts and tolerability. The study will include a review of the safety data by a Data Safety Monitoring Board.

Conditions

Purpura, Thrombocytopaenic, Idiopathic

Keywords

idiopathic thrombocytopenic purpura; thrombocytopenia; pharmacodynamics; ITP; eltrombopag; pharmacokinetics; chronic ITP; pediatrics

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving a Platelet Count >=50 Giga Cells Per Liter (Gi/L) at Least Once, Between Day 8 and Day 43 (Weeks 1 to 6) of the Randomized Period of the Study (Part 2)

  Participants who achieved a platelet count \>=50 Gi/L at least once between Day 8 and Day 43 (first 6 weeks of Part 2) in the absense of rescue treatment were reported. A 95% confidence interval was calculated by the exact binomial method.

  From Day 8 up to Day 43 of Part 2

Secondary Outcomes (39)

• Percentage of Participants Achieving Platelet Counts >=50Gi/L During Treatment With Eltrombopag in >= 60% of Assessments Between Day 15 and Day 43 (Weeks 2 Through 6) of the Randomized Treatment Period (Part 2)

  Between Day 15 and Day 43 of Part 2

• Weighted Mean Platelet Count

  Baseline and Day 43 of Part 2

• Percentage of Participants Achieving Platelet Counts >=50Gi/L at Any Time During the 24 Weeks of Eltrombopag Dosing During Part 1.

  From Day 1 of treatment up to Week 24 of Part 1

• Percentage of Participants Achieving Platelet Counts >=50 Gi/L at Any Time During the 31 Weeks of Eltrombopag Treatment During Part 2/ 3.

  Part 2/3 up to Study Week 31

• Population Pharmacokinetic (PK) Assessment for Eltrombopag for AUC(0-t) During Part 1, 2, and 2/3.

  From Day 1 of treatment up to Study Week 31

Study Arms (2)

eltrombopag plus standard of care

EXPERIMENTAL

eltrombopag

Drug: eltrombopag

placebo plus standard of care

PLACEBO COMPARATOR

placebo

Drug: Placebo

Interventions

eltrombopag DRUG

thrombopoietin receptor agonist

eltrombopag plus standard of care

Placebo DRUG

placebo for comparison

placebo plus standard of care

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subjects between 1 year and \<18 years of age at Day 1.
• Written informed consent from subject's guardian and accompanying informed assent from subject (for children over 6 years old).
• Confirmed diagnosis of chronic ITP, according to the American Society of Hematology / British Committee for Standards in Haematology (ASH/BCSH) guidelines \[George, 1996; BCSH, 2003\]. In addition, a peripheral blood smear or bone marrow examination should support the diagnosis of ITP with no evidence of other causes of thrombocytopenia.
• Subjects who are refractory or have relapsed after at least one prior ITP therapy or are not eligible, for a medical reason, for other treatments.
• 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 have been clearly ineffective.
• Subjects 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.
• Previous treatment for ITP with splenectomy, rituximab and cyclophosphamide must have been completed at least 4 weeks prior to Day 1 or have clearly been ineffective.
• Subjects must have prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) within 80 to 120% of the normal range.
• Subjects must have a complete blood count (CBC) not suggestive of another hematological disorder.
• The following clinical chemistries for the subjects MUST NOT exceed the upper limit of normal (ULN) reference range by more than 20%: creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and alkaline phosphatase. In addition, total albumin must not be below the lower limit of normal (LLN) by more than 10%.
• For subjects of child-bearing potential (after menarche): subject must not be sexually active or is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subjects) must use one of the following highly effective methods of contraception (i.e., Pearl Index \<1.0%) from two weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study:
• Complete abstinence from intercourse;
• Intrauterine device (IUD);
• Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide);

You may not qualify if:

• 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).
• Concurrent or past malignant disease, including myeloproliferative disorder.
• Subjects who are not suitable for continuation of their current therapy for at least 7 additional additional weeks.
• Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding Day 1.
• History of platelet agglutination abnormality that prevents reliable measurement of platelet counts.
• 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.
• Subject with Evans syndrome (autoimmune thrombocytopenia and autoimmune hemolysis).
• Subjects with known inherited thrombocytopenia (e.g. MYH-9 disorders)
• Subjects treated with drugs that affect 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.
• Subjects who have previously received eltrombopag or any other thrombopoietin receptor agonist.
• For female subjects who have reached menarche status, an inability or unwillingness to provide a blood or urine specimen for pregnancy testing.
• Female subjects who are pregnant or lactating.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (33)

GSK Investigational Site

Phoenix, Arizona, 85016, United States

Location

GSK Investigational Site

Orange, California, 92868, United States

Location

GSK Investigational Site

Jacksonville, Florida, 32207, United States

Location

GSK Investigational Site

Orlando, Florida, 32806, United States

Location

GSK Investigational Site

Orlando, Florida, 32827, United States

Location

GSK Investigational Site

Chicago, Illinois, 60611-2605, United States

Location

GSK Investigational Site

Peoria, Illinois, 61614, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02115, United States

Location

GSK Investigational Site

Albuquerque, New Mexico, 87106, United States

Location

GSK Investigational Site

New York, New York, 10021, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28203, United States

Location

GSK Investigational Site

Durham, North Carolina, 27710, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45229, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15224, United States

Location

GSK Investigational Site

Memphis, Tennessee, 38105, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Seattle, Washington, 98105, United States

Location

GSK Investigational Site

Toronto, Ontario, M5G 1X8, Canada

Location

GSK Investigational Site

Montreal, Quebec, H3T 1C5, Canada

Location

GSK Investigational Site

Bordeaux, 33076, France

Location

GSK Investigational Site

Paris, 75571, France

Location

GSK Investigational Site

Paris, 75935, France

Location

GSK Investigational Site

Rotterdam, 3015 GJ, Netherlands

Location

GSK Investigational Site

Barakaldo (Vizcaya), 48903, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Madrid, 28009, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Cardiff, CF14 4XW, United Kingdom

Location

GSK Investigational Site

London, W2 1NY, United Kingdom

Location

GSK Investigational Site

Manchester, M13 9WL, United Kingdom

Location

GSK Investigational Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

GSK Investigational Site

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (3)

• Grainger JD, Blanchette VS, Grotzinger KM, Roy A, Bussel JB. Health-related quality of life in children with chronic immune thrombocytopenia treated with eltrombopag in the PETIT study. Br J Haematol. 2019 Apr;185(1):102-106. doi: 10.1111/bjh.15732. Epub 2018 Dec 27.

  PMID: 30592022 DERIVED

• 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.

  PMID: 29536526 DERIVED

• Bussel JB, de Miguel PG, Despotovic JM, Grainger JD, Sevilla J, Blanchette VS, Krishnamurti L, Connor P, David M, Boayue KB, Matthews DC, Lambert MP, Marcello LM, Iyengar M, Chan GW, Chagin KD, Theodore D, Bailey CK, Bakshi KK. Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study. Lancet Haematol. 2015 Aug;2(8):e315-25. doi: 10.1016/S2352-3026(15)00114-3. Epub 2015 Jul 28.

  PMID: 26688484 DERIVED

MeSH Terms

Conditions

Purpura; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Purpura, Thrombocytopenic; Thrombotic Microangiopathies; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2009
• First Posted: May 25, 2009
• Study Start: September 30, 2009
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: October 12, 2018
• Results First Posted: October 31, 2014

Record last verified: 2015-03

Locations

ES (4); GB (5); CA (2); US (18); FR (3); NL (1)