Clinical trial NCT01520909: 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.
Official title: A Two Part, Double-blind, Randomized, Placebo-controlled and Open-label Study to Investigate the Efficacy, Safety and Tolerability of Eltrombopag, a Thrombopoietin Receptor Agonist, in Pediatric Patients With Previously Treated Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP). PETIT2: Eltrombopag in PEdiatric Patients With Thrombocytopenia From ITP
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Idiopathic Thrombocytopenic Purpura
Keywords: immune thrombocytopenic purpura
pediatrics
chronic ITP
idiopathic thrombocytopenic purpura
eltrombopag
Chronic Immune Thrombocytopenia
platelet disorder
thrombocytopenia
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-01-30
Enrollment: 92
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants Achieving a Platelet Count >=50 Giga Cells Per Liter (Gi/L) for at Least 6 Out of 8 Weeks, Between Weeks 5 and 12 of Part 1
timeFrame: From Week 5 up to Week 12 of Part 1
Secondary outcomes:
measure: Percentage of Responders
timeFrame: From Week 1 up to Week 12 of Part 1
measure: Number of Participants Achieving a Platelet Count >=50 Gi/L at Any Time During the First 12 Weeks of Part 1
timeFrame: From Baseline up to Week 12 of Part 1
measure: Number of Participants Achieving a Platelet Count >=50 Gi/L at Any Time During the First 6 Weeks of Part 1
timeFrame: From Baseline up to Week 6 of Part 1
measure: Weighted Mean Platelet Count
timeFrame: Baseline and Week 12 of Part 1
measure: Maximum Duration for Which a Participant Continuously Maintained a Platelet Count of >=50 Gi/L During the First 12 Weeks of Part 1
timeFrame: From Baseline up to Week 12 of Part 1
measure: Number of Participants Who Required a Protocol-defined Rescue Treatment During Part 1
timeFrame: From Baseline up to Week 12 of Part 1
measure: Number of Participants With Any Bleeding and Significant Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale During Part 1
timeFrame: From Baseline through Follow-up of Part 1
measure: Number of Participants Who Achieved a Platelet Count >=50 Gi/L at Any Time During Part 2
timeFrame: From Baseline up to Week 24 of Part 2
measure: Number of Weeks in Which Participants Achieved a Platelet Count >=50 Gi/L, Between Weeks 4 and 24 of Part 2
timeFrame: From Week 4 up to Week 24 of Part 2
measure: Maximum Duration for Which a Participant Continuously Maintained a Platelet Count of >=50 Gi/L During Part 2
timeFrame: From Baseline up to Week 24 of Part 2
measure: Number of Participants Who Reduced or Discontinued Baseline Concomitant ITP Medications During Part 2 Without Requiring Subsequent Rescue Therapy
timeFrame: From Baseline up to Week 24 of Part 2
measure: Number of Participants Who Required a Protocol-defined Rescue Treatment During Part 2
timeFrame: From Baseline up to Week 24 of Part 2
measure: Number of Participants With Any Bleeding and Significant Bleeding as Assessed Using the WHO Bleeding Scale During Part 2
timeFrame: From Baseline of Part 2 through Follow-up
measure: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 1
timeFrame: From Day 1 of Treatment up to Week 13 of Part 1+ 1 day
measure: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 2
timeFrame: From Day 1 of Part 2 up to Week 24 of Part 2 + 1 day
measure: Number of Participants With the Indicated Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters at Any Time Post-Baseline During Part 1
timeFrame: From Baseline up to Week 13 of Part 1
measure: Number of Participants With the Indicated Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters at Any Time Post-Baseline During Part 2
timeFrame: From Baseline (BL) of Part 2 through Follow-up
measure: Number of Participants With the Indicated Maximum Toxicity Grade for the Indicated Hematology Parameters at Any Time Post-Baseline During Part 1
timeFrame: From Baseline up to Week 13 of Part 1
measure: Number of Participants With the Indicated Maximum Toxicity Grade for the Indicated Hematology Parameters at Any Time Post-Baseline During Part 2
timeFrame: From Baseline up to Week 24 of Part 2 and Follow-up Weeks 1 to 4 (up to Study Week 41)
measure: Number of Participants With Vital Sign Data Falling Outside the Reference Ranges (RR) at the Indicated Visit During Part 1
timeFrame: From Screening (SCR) up to Week 13 of Part 1
measure: Number of Participants With Vital Sign Data Falling Outside the Reference Ranges (RR) at the Indicated Visit During Part 2
timeFrame: From Week 1 up to Week 24 of Part 2 and Follow-up Week 1 to Week 4 (up to Week 41)
measure: Number of Participants With a Change in Visual Acuity Since Baseline at Week 12 of Part 1
timeFrame: Baseline and Week 12 of Part 1
measure: Number of Participants With a Change in Visual Acuity Since Baseline at Week 24 of Part 2
timeFrame: Baseline and Week 24 of Part 2
measure: Number of Participants With a Change in Visual Acuity Since Baseline at Follow-Up Week 24
timeFrame: Baseline and Follow-Up Week 24 (Study Week 61)
measure: Number of Participants With Worsening Visual Acuity Due to Cataracts at Week 12 of Part 1
timeFrame: Baseline and Week 12 of Part 1
measure: Number of Participants With Worsening Visual Acuity Due to Cataracts at Week 24 of Part 2
timeFrame: Baseline and Week 24 of Part 2
measure: Number of Participants With Worsening Visual Acuity Due to Cataracts at Follow-Up Week 24
timeFrame: Baseline and Follow-Up Week 24 (Week 61)
measure: Pharmacokinetic (PK) Assessments for Eltrombopag for AUC (0-t)
timeFrame: Part 1 Weeks 2, 4, 6, 8, 10, 12, and Part 2 Weeks 1-12 (Study Weeks 13 - 37)
measure: Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax
timeFrame: Part 1 Weeks 2, 4, 6, 8, 10, 12, and Part 2 Weeks 1-12 (Study Weeks 13 - 37)
measure: Pharmacokinetic (PK) Assessments for Eltrombopag for Apparent Oral Clearance (CL/F) and Apparent Intercompartmental Clearance (Q/F)
timeFrame: Part 1 Weeks 2, 4, 6, 8, 10, 12, and Part 2 Weeks 1-12 (Study Weeks 13 - 37)
measure: PK Assessments for Eltrombopag for Apparent Central Volume (Vc/F) and Apparent Peripheral Volume (Vp/F)
timeFrame: Part 1 Weeks 2, 4, 6, 8, 10, 12, and Part 2 Weeks 1-12 (Study Weeks 13 - 37)
measure: Population PK Model Point Estimate for Eltrombopag for Absorption Rate-constant (Ka)
timeFrame: Part 1 Weeks 2, 4, 6, 8, 10, 12, and Part 2 Weeks 1-12 (Study Weeks 13 - 37)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: St. Petersburg
country: United States
facility: GSK Investigational Site
state: Florida
city: Brooklyn
country: United States
facility: GSK Investigational Site
state: New York
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Capital Federal
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Brno
country: Czech Republic
facility: GSK Investigational Site
city: Olomouc
country: Czech Republic
facility: GSK Investigational Site
city: Ostrava
country: Czech Republic
facility: GSK Investigational Site
city: Praha 5
country: Czech Republic
facility: GSK Investigational Site
city: Freiburg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Pokfulam
country: Hong Kong
facility: GSK Investigational Site
city: Shatin
country: Hong Kong
facility: GSK Investigational Site
city: Beer-Sheva
country: Israel
facility: GSK Investigational Site
city: Haifa
country: Israel
facility: GSK Investigational Site
city: Petah-Tikva
country: Israel
facility: GSK Investigational Site
city: Ramat Gan
country: Israel
facility: GSK Investigational Site
city: Rehovot
country: Israel
facility: GSK Investigational Site
city: Tel-Aviv
country: Israel
facility: GSK Investigational Site
city: Bologna
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Monza
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Torino
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Gdansk
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Lublin
country: Poland
facility: GSK Investigational Site
city: Krasnodar
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Murcia (El Palmar)
country: Spain
facility: GSK Investigational Site
city: Málaga
country: Spain
facility: GSK Investigational Site
city: Pamplona
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Tainan
country: Taiwan
facility: GSK Investigational Site
city: Taoyuan
country: Taiwan
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
city: Songkla
country: Thailand
facility: GSK Investigational Site
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: Cardiff
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
city: Romford
country: United Kingdom
facility: GSK Investigational Site
city: Sheffield
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.