A study of a new medication, eltrombopag, for the treatment of childhood chronic immune thrombocytopenic purpura (ITP), a blood disorder of low platelet counts that can lead to bruising easily, bleeding gums, and/or bleeding inside the body.

• Register: EUCTR
• Last refreshed on: 20 March 2012
• Main ID: EUCTR2006-002946-13-Outside-EU/EEA
• Date of registration: 24/02/2012
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Limited
• Public title: A study of a new medication, eltrombopag, for the treatment of childhood chronic immune thrombocytopenic purpura (ITP), a blood disorder of low platelet counts that can lead to bruising easily, bleeding gums, and/or bleeding inside the body.
• Scientific title: A three part, staggered cohort, open-label and double blind, randomized, placebo controlled study to investigate the efficacy, safety, tolerability and pharmacokinetics of eltrombopag, a thrombopoietin receptor agonist, in previously treated pediatric patients with chronic idiopathic thrombocytopenic purpura (ITP). Eltrombopag PETIT: Eltrombopag in PEdiatric patients with Thrombocytopenia from ITP - PETIT
• Target sample size: 70
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-002946-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Canada, United States

Contacts

• Name: Clinical Trial Helpdesk
• Affiliation: GlaxoSmithKline Research & Development Limited

• Name: Clinical Trial Helpdesk
• Affiliation: GlaxoSmithKline Research & Development Limited

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subjects between 1 year and <18 years of age at Day 1.
2. Written informed consent from subject’s guardian and accompanying informed assent from subject (for children over 6 years old).
3. 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.
4. 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.
5. Day 1 (or within 48 hours prior) platelet count <30 Gi/L.
6. 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.
7. 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.
8. 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.
9. Subjects must have prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) within 80 to 120% of the normal range.
10. Subjects must have a complete blood count (CBC) not suggestive of another hematological disorder.
11. The following clinical chemistries for the subjects MUST NOT exceed the upper limit of normal (ULN) reference range by more than 20%: creatinine, ALT, AST, total bilirubin, and alkaline phosphatase. In addition, total albumin must not be below the lower limit of normal (LLN) by more than 10%.
12. 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);
• Systemic contraceptives (combined or progesterone only).

Are the trial subjects under 18? yes
Number of subjects for this age range: 70
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. 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).
2. Concurrent or past malignant disease, including myeloproliferative disorder.
3. Subjects who are not suitable for continuation of their current therapy for at least 7 additional weeks.
4. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding Day 1.
5. History of platelet agglutination abnormality that prevents reliable measurement of platelet counts.
6. 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.
7. Subject with Evans syndrome (autoimmune thrombocytopenia and autoimmune hemolysis).
8. Subjects with known inherited thrombocytopenia (e.g. MYH-9 disorders)
9. 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.
10. Subjects who have previously received eltrombopag or any other thrombopoietin receptor agonist.
11. For female subjects who have reached menarche status, an inability or unwillingness to provide a blood or urine specimen for pregnancy testing.
12. Female subjects who are pregnant or lactating.
13. In France, a subject is neither affiliated with nor a beneficiary of a social security category.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Idiopathic Thrombocytopenic Purpura
MedDRA version: 14.1 Level: PT Classification code 10021245 Term: Idiopathic thrombocytopenic purpura System Organ Class: 10005329 - Blood and lymphatic system disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Eltrombopag
Product Code: SB-497115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Eltrombopag
CAS Number: 496775-62-3
Current Sponsor code: SB-497115
Other descriptive name: REVOLADE, PROMACTA
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 12.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use
Pharmaceutical form of the placebo: Powder and solvent for oral suspension
Route of administration of the placebo: Oral use

Product Name: Eltrombopag
Product Code: SB-497115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Eltrombopag
CAS Number: 496775-62-3
Current Sponsor code: SB-497115
Other descriptive name: REVOLADE, PROMACTA
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use
Pharmaceutical form of the placebo: Powder and solvent for oral suspension
Route of administration of the placebo: Oral use

Product Name: Eltrombopag
Product Code: SB-497115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Eltrombopag
CAS Number: 496775-62-3
Current Sponsor code: SB-497115
Other descriptive name: REVOLADE, PROMACTA
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use
Pharmaceutical form of the placebo: Powder and solvent for oral suspension
Route of administration of the placebo: Oral use

Product Name: Eltrombopag
Product Code: SB-497115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Eltrombopag
CAS Number: 496775-62-3
Current Sponsor code: SB-497115
Other descriptive name: REVOLADE, PROMACTA
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Film-c

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Between Days 8 and 43 of the randomized period of the study.

Primary end point(s): Proportion of subjects achieving platelet counts =50Gi/L at least once between days 8 and 43 of the randomized period of the study.

Secondary Objective: •To describe the safety and tolerability of eltrombopag when administered for 24 weeks
•To characterize the PK profile of eltrombopag in pediatric subjects
•To describe the efficacy of eltrombopag in achieving platelet counts = 50Gi/L when administered for 24 weeks
•To describe the effect of eltrombopag on reduction and/or interruption of concomitant ITP therapies, when administered for 24 weeks
•To describe the effect of eltrombopag on the need for rescue ITP medication when administered to previously treated pediatric subjects
•To assess the impact of eltrombopag on the incidence and severity of bleeding symptoms when administered in previously treated pediatric patients
•To evaluate the impact of eltrombopag on the quality of life of previously treated pediatric patients

Main Objective: To assess the efficacy of eltrombopag, relative to placebo, in achieving a platelet count =50Gi/L at any time during a 6 week treatment period when administered to previously treated pediatric subjects with chronic ITP.

Secondary Outcome(s)

Secondary end point(s): - Proportion of subjects with platelet counts =50 Gi/L during treatment with eltrombopag in = 60% of assessments between days 15 and 43 of the randomized treatment period.
- Weighted mean platelet change (area under the platelet-time curve divided by duration) from baseline to day 43 of the randomized period
- Proportion of subjects achieving platelet counts =50 Gi/L at any time during the 24 weeks of eltrombopag dosing.
- Plasma eltrombopag AUC(0-t), Cmax, tmax, Ct, CL/F.
- Safety and tolerability parameters including blood pressure, respiratory and heart rate, ocular examinations, clinical laboratory assessments and frequency of all adverse events, categorized using Common Terminology Criteria for Adverse Events (CTCAE) v3 toxicity grades. Ocular examinations will include 3 and 6 months after completion of therapy
- Maximum period of time with platelet count continuously =50 Gi/L during the 24 weeks of eltrombopag dosing for subjects participating in Parts 2 and 3
- The proportion of subjects that reduced or discontinued baseline concomitant ITP medications while receiving eltrombopag during 24 weeks for subjects entering the randomized period.
- The proportion of subjects that required protocol-defined rescue treatment during the study period
- Impact on Quality of Life (subject and care giver reported outcomes) will be measured using the Kids’ ITP Tools (KIT) questionnaire
-The ability to reduce bleeding symptoms associated with ITP based on the WHO Bleeding Scale.

Timepoint(s) of evaluation of this end point: Timepoints span from baseline to day 43 of the randomized treatment period, up to 24 weeks of dosing and at 3 & 6 months after completion of therapy

Secondary ID(s)

2006-002946-13-ES

NCT00908037

TRA108062

Source(s) of Monetary Support

GlaxoSmithKline Research & Development Limited