Clinical Trial: 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.

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Patie

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 Summary: 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.
Sponsor: GlaxoSmithKline

Current Primary Outcome: 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 [ Time Frame: From Week 5 up to Week 12 of Part 1 ]

Original Primary Outcome: The odds of achieving platelet counts ≥ 50 Gi/L [ Time Frame: 12 weeks in Part 1 ]

Current Secondary Outcome:

• Percentage of Responders [ Time Frame: From Week 1 up to Week 12 of Part 1 ]
  Percentage of participants who responded (defined as platelet count >= 50 Gi/L in absence of rescue) at least once up to week 12 of Part 1 (Odds of achieving a platelet count >=50 Gi/L during the first 12 weeks of Part 1)
• Number of Participants Achieving a Platelet Count >=50 Gi/L at Any Time During the First 12 Weeks of Part 1 [ Time Frame: From Baseline up to Week 12 of Part 1 ]
  Participants who achieved a platelet count >=50 Gi/L at any time during the first 12 weeks of Part 1 were reported.
• Number of Participants Achieving a Platelet Count >=50 Gi/L at Any Time During the First 6 Weeks of Part 1 [ Time Frame: From Baseline up to Week 6 of Part 1 ]
  Participants who achieved a platelet count >=50 Gi/L at any time during the first 6 weeks of Part 1 were reported.
• Weighted Mean Platelet Count [ Time Frame: Baseline and Week 12 of Part 1 ]
  The weighted mean platelet count is defined as "the area under the platelet-time curve divided by the duration of the study (12 weeks)". Weighted mean platelet counts from baseline to week 12 of the randomized period was compared between placebo and eltrombopag using an analysis of covariance model (ANCOVA) adjusting for baseline platelet count and age cohort. For each subject the area between two adjacent visits with platelet counts was calculated. The area was calculated for all pairs of adjacent visits starting at Day 1 of randomized period and then the total sum of all the areas was divided by the total duration of time during the randomized period. For each subject, this method calculates an 'average' platelet count and it allows the possibility that subjects may have had different number of assessments during different times relative to baseline.
• Maximum Duration for Which a Participant Continuously Maintained a Platelet Count of >=50 Gi/L During the First 12 Weeks of Part 1 [ Time Frame: From Baseline up to Week 12 of Part 1 ]
  The maximum duration for which a participant continuously maintained a platelet count >=50 Gi/L was calculated and summarized for the first 12 weeks of Part 1. Participants with non-weekly assessments were assumed to have maintained a positive response for each week between two assessments that had positive responses. If a participant achieved a positive response at an assessment and then achieved a negative response at the next assessment, then it was assumed that the participant had achieved a positive response for one day.
• Number of Participants Who Required a Protocol-defined Rescue Treatment During Part 1 [ Time Frame: From Baseline up to Week 12 of Part 1 ]
  Rescue treatment is defined as either a new immune (idiopathic) thrombocytopenic purpura (ITP) medication, an increase in the dose of a concomitant ITP medication from Baseline, a platelet transfusion, or a splenectomy.
• Number of Participants With Any Bleeding and Significant Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale During Part 1 [ Time Frame: From Baseline through Follow-up of Part 1 ]
  The WHO Bleeding Scale is a measure of bleeding severity with the following grades: Grade 0=no bleeding; Grade 1=petechiae; Grade 2=mild blood loss; Grade 3=gross bleeding; Grade 4=debilitating blood loss. The WHO grades were dichotomized into the following categories: no bleeding=Grade 0; any bleeding=Grades 1 to 4; no clinically significant bleeding=Grades 0 to 1; clinically significant bleeding=Grades 2 to 4. Baseline was defined as the Day 1 assessment or the latest possible screening assessment.
• Number of Participants Who Achieved a Platelet Count >=50 Gi/L at Any Time During Part 2 [ Time Frame: From Baseline up to Week 24 of Part 2 ]
  Participants who achieved a platelet count >=50 Gi/L at any time during Part 2 (up to Week 24) were reported.
• Number of Weeks in Which Participants Achieved a Platelet Count >=50 Gi/L, Between Weeks 4 and 24 of Part 2 [ Time Frame: From Week 4 up to Week 24 of Part 2 ]
  Platelet response was analyzed after Week 4 for the eltrombopag-only period to allow participants who had been randomized to placebo in the Randomized Period time to escalate to their optimal dose of eltrombopag. Participants with non-weekly assessments were assumed to have maintained a positive response for each week between two assessments that had positive responses. If the participant achieved a positive response at an assessment and then achieved a negative response at the next assessment, then it was assumed that the participant had achieved a positive response for one day.
• Maximum Duration for Which a Participant Continuously Maintained a Platelet Count of >=50 Gi/L During Part 2 [ Time Frame: From Baseline up to Week 24 of Part 2 ]
  The maximum duration for which a participant continuously maintained a platelet count of >=50 Gi/L was calculated and sum
  
  

  Original Secondary Outcome:

  • The proportion of patients who achieve platelet counts ≥ 50 Gi/L [ Time Frame: Weeks 5-12 of Part 1 ]
    Percentage of patients of achieve platelet count of greater or equal to 50 Gi/L
  • Weighted mean platelet change (area under the platelet-time curve divided by duration) [ Time Frame: first 12 weeks in Part 1 ]
    Area under the platelet-time curve divided by the duration of treatment with study medication
  • The proportion of patients who achieve platelet counts ≥ 50 Gi/L at any time during the first 6 weeks of Part 1. [ Time Frame: first 6 weeks in Part 1 ]
    Percentage of patients of achieve a platelet count of greater or equal to 50 Gi/L
  • The proportion of patients who achieve platelet counts ≥ 50 Gi/L at any time during the first 12 weeks of Part 1. [ Time Frame: first 12 weeks in Part 1 ]
    Percentage of patients of achieve a platelet count of greater or equal to 50 Gi/L
  • The proportion of patients who achieve platelet counts ≥ 50 Gi/L at any time during Part 2. [ Time Frame: 24 weeks (Part 2) ]
    Percentage of patients of achieve a platelet count of greater or equal to 50 Gi/L
  • Maximum period of time with platelet counts continuously ≥ 50 Gi/L during the first 12 weeks of Part 1. [ Time Frame: first 12 weeks in Part 1 ]
    Number of weeks with platelet counts continuously greater than or equal to 50 Gi/L
  • The proportion of weeks in which platelet counts ≥ 50 Gi/L, between weeks 4-24 of Part 2. [ Time Frame: Weeks 4-24 of Part 2 ]
    Percentage of weeks with platelet counts greater than or equal to 50 Gi/L
  • Maximum period of time with platelet counts continuously ≥ 50 Gi/L during Part 2. [ Time Frame: 24 weeks (Part 2) ]
    Number of weeks with platelet counts continuously greater than or equal to 50 Gi/L
  • The proportion of patients who reduced or discontinued baseline concomitant ITP medications during Part 2. [ Time Frame: 24 weeks (Part 2) ]
    The percentage of patients who stopped or reduced dose of other ITP medications
  • The proportion of patients who required protocol-defined rescue treatment during Part 1. [ Time Frame: 13 weeks (Part 1) ]
    The percentage of patients who required rescue treatment for ITP
  • The proportion of patients who required protocol-defined rescue treatment during Part 2. [ Time Frame: 24 weeks (Part 2) ]
    The percentage of patients who required rescue treatment for ITP
  • Incidence and severity of symptoms associated with ITP, including bleeding, bruising and petechiae, measured using the World Health Organization (WHO) Bleeding Scale during Part 1. [ Time Frame: 13 weeks (Part 1) ]
    Change in score on the WHO bleeding scale
  • Incidence and severity of symptoms associated with ITP, including bleeding, bruising and petechiae, measured using the World Health Organization (WHO) Bleeding Scale during Part 2. [ Time Frame: 24 weeks (Part 2) ]
    Change in score on the WHO bleeding scale
  • Frequency of adverse events [ Time Frame: 61 weeks (Part 1, Part 2 and follow-up period) ]
    Proportion of patients reporting any adverse event
  • Clinical Laboratory Assessments (clinical chemistry tests, coagulation parameters, hematology tests, peripheral blood smear, and urinalysis tests) [ Time Frame: 37 weeks (Part 1 and Part 2) ]
    Change in clinical chemistry, coagulation, hematology, peripheral blood smear or urinalysis tests.
  • Ophthalmic Examination (visual acuity, intraocular pressure, lens opacity measured using the AREDS scale) [ Time Frame: 61 weeks (Part 1, Part 2 and follow-up period) ]
    Change in visual acuity, intraocular pressure, opacity of the lens (AREDS score).
  • Vital signs including Blood pressure (systolic/diastolic) and pulse [ Time Frame: 37 weeks (Part 1 and Part 2) ]
    Change in blood pressure (systolic and diastolic blood pressure values) or heart rate (pulse).
  • Apparent clearance following oral dosing (CL/F) of eltrombopag [ Time Frame: 37 weeks (Part 1 and Part 2) ]
    Population pharmacokinetic measure
  • Intercompartmental clearence (Q/F) of eltrombopag [ Time Frame: 37 weeks (Part 1 and Part 2) ]
    

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