Efficacy of Eltrombopag to Improve Thrombocytopenia of MYH9-related Disease

Phase 2

Completed

• Conditions: Blood Platelet Disorders
• Interventions: Drug: eltrombopag

• Registration Number: NCT01133860
• Lead Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-01
• Study First Submitted: 2010-05-28
• Study First Submitted QC: 2010-05-28
• Study First Posted: 2010-05-31
• Primary Completion: 2010-06
• Study Completion: 2010-06
• Status Verified: 2010-07
• Results First Submitted: 2011-06-22
• Results First Submitted QC: 2011-06-22
• Results First Posted: 2011-07-21
• Last Update Submitted: 2011-07-22
• Last Update Posted: 2011-07-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Age 16 years or more
• Confirmed diagnosis of MYH9-related disease
• Average platelet count for the previous year less than 50x10e9/L
• Written informed consent

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Exclusion Criteria

• Diseases known to involve the risk of thromboembolic events (e.g. atrial fibrillation)
• History of thrombosis within 1 year
• Use of drugs that affect platelet function (including but not limited to, aspirin, clopidogrel or NSAIDS) or anti-coagulants
• Females who are pregnant or nursing (a negative pregnancy test in required before enrollment of fertile women)
• Formal refusal of any recommendation of a safe contraception
• Alcohol or drug addiction
• Altered renal function as defined by creatinine of 20 mg/L or more
• Any other disease or condition that by the advise of the responsible physician would make the treatment dangerous for the patient or would make the patient ineligible for the study, including physical, psychiatric, social and behavioral problems. HCV positivity and liver diseases will not be considered an exclusion criterion since a phase II study showed that eltrombopag was effective and safe in this patient population.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
eltrombopag	eltrombopag	-

Primary Outcome Measures

Name	Time	Method
Response to Drug Based on Platelet Count at the End of Therapy	21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy	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.

Secondary Outcome Measures

Name	Time	Method
Bleeding Tendency Assessed by WHO Bleeding Score	21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy	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	21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy	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	21 days or 42 days of therapy	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

Trial Locations

Locations (3)

Azienda Ospedaliero-Universitaria di Padova, Unità di Medicina Generale e Patologia Speciale; 🇮🇹 Padova, Italy

Fondazione IRCCS Policlinico San Matteo, Unità di Medicina III; 🇮🇹 Pavia, Italy

Policlinico Monteluce, Sezione di Medicina Interna e Cardiovascolare; 🇮🇹 Perugia, Italy