Efficacy of Eltrombopag to Improve Thrombocytopenia of MYH9-related Disease
The term MYH9-related disease (MYH9RD) includes four genetic disorders: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome. All these disorders derive from mutation of a unique gene, named MYH9, and they have been recognized as different clinical presentations of a single illness that was named MYH9RD. All patients affected by MYH9RD present since birth with thrombocytopenia, which can result in a variable degree of bleeding diathesis; some of them subsequently develop additional clinical manifestations, such as renal damage, sensorineural hearing loss, and/or presenile cataracts. Eltrombopag is an oral thrombopoietin receptor agonist that stimulates proliferation and differentiation of megakaryocytes, the bone marrow cells that produce blood platelets. This drug is effective in increasing platelet count in healthy volunteers, as well as in patients affected by some acquired thrombocytopenias, such as idiopathic thrombocytopenic purpura and HCV related thrombocytopenia. The purpose of this study is to determine if eltrombopag, administered orally at the dose of 50 or 75 mg/daily for up to 6 weeks, is effective in increasing platelet count of patients affected by MYH9RD. Further aims of this study are to test if eltrombopag is effective in reducing bleeding tendency of MYH9RD patients; to evaluate safety and tolerability of eltrombopag in patients with MYH9RD; to evaluate in vitro function of platelets produced during therapy in patients responding to this drug.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Exploratory Phase II Dose Escalation Study of Eltrombopag in MYH9 Related Disease|
- Response to Drug Based on Platelet Count at the End of Therapy [ Time Frame: 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy ] [ Designated as safety issue: No ]The primary endpoints were the achievement of a platelet count over 100 x10e9/L or at least 3 times the baseline value (major response), or at least twice the baseline value but less than major response (minor response). The overall response to therapy is reported. Platelet count was measured at the end of therapy (21 or 42 days, see study design) by phase-contrast microscopy.
- Bleeding Tendency Assessed by WHO Bleeding Score [ Time Frame: 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy ] [ Designated as safety issue: No ]The percentage of patients with bleeding diathesis (grade 1, i.e. cutaneous bleeding, or grade 2, i.e. mild blood loss, according to WHO bleeding score) was calculated at baseline and at the end of therapy. The results are expressed as the mean change in the percentage of patients with bleeding diathesis (95%CI).
- All Types of Adverse Events [ Time Frame: 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy ] [ Designated as safety issue: Yes ]All type of adverse events were registered.Results indicate the number of participants who experience a side effect of the drug.
- in Vitro Function of Platelets Produced During Therapy in Responding Patients [ Time Frame: 21 days or 42 days of therapy ] [ Designated as safety issue: No ]in vitro platelet function will be assessed in patients achieving a platelet count of 100 x10e9/L or more at the end of the therapy
|Study Start Date:||January 2009|
|Study Completion Date:||June 2010|
|Primary Completion Date:||June 2010 (Final data collection date for primary outcome measure)|
Eltrombopag, administered orally, 50 mg/daily for 21 days. Patients with platelet counts between 100 and 150x10e9/L at day 21 will continue eltrombopag 50 mg/daily for 21 additional days. Patients with platelet count lower than 100x10e9/L at day 21 will receive eltrombopag 75 mg/daily for additional 21 days. Patients with more than 150x10e9 platelets/L at day 21 will stop therapy.
|Azienda Ospedaliero-Universitaria di Padova, Unità di Medicina Generale e Patologia Speciale|
|Padova, Italy, 35128|
|Fondazione IRCCS Policlinico San Matteo, Unità di Medicina III|
|Pavia, Italy, 27100|
|Policlinico Monteluce, Sezione di Medicina Interna e Cardiovascolare|
|Perugia, Italy, 06122|
|Principal Investigator:||Carlo Balduini, MD||IRCCS Policlinico San Matteo Foundation, Pavia, Italy|