Clinical Trial: A Longitudinal 2-year Bone Marrow Study of Eltrombopag in Previously Treated Adults, With Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP)

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

Official Title: A Longitudinal 2-year Bone Marrow Study of Eltrombopag Olamine (SB-497115-GR) in Previously Treated Adults, With Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP)

Brief Summary: A open-label, multi-center 2-year safety study to ascertain the baseline levels of bone marrow fibers in previously treated adults with chronic immune (idiopathic) thrombocytopenic purpura (ITP) and to evaluate the long-term effect of eltrombopag on bone marrow fibers. The study will also describe the long-term safety and tolerability of oral eltrombopag treatment in subjects with chronic ITP.

Detailed Summary:

This is a phase IV, open-label safety study, designed to determine baseline levels of bone marrow fibers in previously treated adults with chronic immune (idiopathic) thrombocytopenic purpura (ITP)and to evaluate the long-term effect of eltrombopag on bone marrow reticulin and/or collagen fibers.

The duration of the screening period is up to 8 weeks. Eltrombopag will be administered for at least 2-years followed by a 4-week follow-up period. Bone marrow biopsies will be performed at screening, after 1-year and 2-years of eltrombopag treatment, and at early withdrawal of treatment. The screening bone marrow biopsy should be performed within 8 weeks of planned start of study medication and the bone marrow biopsy block must be available for central laboratory processing.


Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Number of Participants With Bone Marrow (BM) Fibers of MF Grade 0, 1, 2 and 3 on the European Consensus (EC) Scale at Baseline [ Time Frame: Baseline ]
    The evaluation of fibrosis was performed using BM biopsies in which the amount of fibrosis was assessed by the EC Grading Scale. This method distinguishes four degrees of fibrosis (myelofibrosis [MF]-0 to MF-3). MF Grade (G) 0 is scattered linear reticulin with no intersections (cross-overs) corresponding to normal BM; MF Grade 1 is loose network of reticulin with many intersections, especially in perivascular areas; MF Grade 2 is diffuse and dense increase in reticulin with extensive intersections, occasionally with only focal bundles of collagen and/or focal osteosclerosis; MF Grade 3 is diffuse and dense increase in reticulin with extensive intersections with coarse bundles of collagen, often associated with significant osteosclerosis. Baseline is defined as the most recent centrally-reviewed BM biopsy prior to first dose of eltrombopag in the study.
  • Number of Participants With a Positive or Negative Collagen Level at Baseline [ Time Frame: Baseline ]
    The number of participants with a positive or negative collagen level was analyzed. Baseline is defined as the most recent centrally-reviewed BM biopsy prior to first dose of eltrombopag in the study.
  • Number of Participants With Indicated Grade Change From Baseline in the EC Grading Scale at 1 Year [ Time Frame: Baseline and 1 year ]
    The change from baseline to on-treatment assessments of European Consensus (EC) scale was analyzed. On-treatment is defined as during the treatment period (including dose interruptions) and up to 1

    Original Primary Outcome:

    • The proportion of subjects with presence or absence of bone marrow fibers at baseline and a change from baseline after 2 years of treatment. [ Time Frame: 2 years ]
    • The proportion of subjects with presence or absence of bone marrow fibers at baseline and a change from baseline after 1 year treatment. [ Time Frame: 1 year ]


    Current Secondary Outcome:

    • Number of Participants With the Indicated Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters at Any Time Post-Baseline During the Study [ Time Frame: From Week 1 up to Week 104 and up to 6 months follow-up (4 weeks for most participants) (up to approximately 2.5 years) ]
      Clinical chemistry parameters were summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0: G0, none; G1, mild; G2, moderate; G3, severe; G4, life-threatening or disabling. Clinical chemistry parameters included: albumin, alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino transferase (AST), total bilirubin, calcium (hypercalcemia), calcium (hypocalcemia), potassium (hyperkalemia), potassium (hypokalemia), sodium (hypernatremia), sodium (hyponatremia), inorganic phosphorus and creatinine. Baseline values were obtained at Day 1. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). The maximum post-Baseline toxicity grade includes any scheduled or unscheduled post-Baseline assessment during.
    • Number of Participants With the Indicated Maximum Toxicity Grade for the Indicated Hematology Parameters at Any Time Post-Baseline During the Study [ Time Frame: From Week 1 up to Week 104 and up to 6 months follow-up (4 weeks for most participants) (up to approximately 2.5 years) ]
      Hematology parameters were summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0: G0, none; G1, mild; G2, moderate; G3, severe; G4, life-threatening or disabling. Hematology parameters included: hemoglobin (increased), hemoglobin (anemia), lymphocyte count (increased), lymphocyte count (decreased), total absolute neutrophil count (ANC), platelet count and white blood cell (WBC) count. Baseline values were obtained at Day 1. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). The maximum post-Baseline toxicity grade includes any scheduled or unscheduled post-Baseline assessment during.
    • Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Started On-therapy + 1 Day, >1 to 30 Days Post Therapy and >30 Days Post Therapy [ Time Frame: From Week 1 up to Week 104 and up to 6 months follow-up (4 weeks for most participants) (up to approximately 2.5 years) ]
      On-therapy + 1 day is defined as AEs started between the first dose of eltrombopag and up to the day after the last dose of eltrombopag; >1 to 30 days post therapy is defined as AEs that started more than 1 day and up to 30 days after the last dose of eltrombopag; >30 days post therapy is defined as AEs started that started more than 30 days after the last dose of eltrombopag. An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or is a congenital anomaly or birth defect. Medical or scientific judgment should be exercised in other situations.


    Original Secondary Outcome: Safety and tolerability parameters including clinical laboratory tests, and incidence of all adverse events. [ Time Frame: 2 years of treatment ]

    Information By: GlaxoSmithKline

    Dates:
    Date Received: March 25, 2010
    Date Started: May 2010
    Date Completion:
    Last Updated: February 26, 2015
    Last Verified: February 2015