Blood Platelet Disorders
Conditions
Keywords
inherited thrombocytopenia, MYH9 mutations, eltrombopag
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.
Interventions
DRUGeltrombopag
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.
Sponsors
University of Pavia
GlaxoSmithKline
Azienda Ospedaliera di Padova
Azienda Ospedaliera di Perugia
Fondazione Telethon
Fondazione IRCCS Policlinico San Matteo di Pavia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Italy
Participant flow
Recruitment details
Patients enrolled between January 2009 and January 2010 as outpatients in medical clinic
Participants by arm
| Arm | Count |
|---|---|
| Eltrombopag Eltrombopag, administered orally, 50 mg/daily for 21 days. Patients with platelet counts between 100 and 150x10e9/L at day 21 continued eltrombopag 50 mg/daily for 21 additional days. Patients with platelet count lower than 100x10e9/L at day 21 received eltrombopag 75 mg/daily for additional 21 days. Patients with more than 150x10e9 platelets/L at day 21 stopped therapy. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Eltrombopag |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Age Continuous | 35.0 years STANDARD_DEVIATION 14.3 |
| Region of Enrollment Italy | 12 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Response to Drug Based on Platelet Count at 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.
Time frame: 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eltrombopag | Response to Drug Based on Platelet Count at the End of Therapy | 91.6 percentage of participants |
Secondary
All Types of Adverse Events
All type of adverse events were registered.Results indicate the number of participants who experience a side effect of the drug.
Time frame: 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eltrombopag | All Types of Adverse Events | 2 number of participants |
Secondary
Bleeding Tendency Assessed by WHO Bleeding Score
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).
Time frame: 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Eltrombopag | Bleeding Tendency Assessed by WHO Bleeding Score | 66.7 participants |
Secondary
in Vitro Function of Platelets Produced During Therapy in Responding Patients
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
Time frame: 21 days or 42 days of therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eltrombopag | in Vitro Function of Platelets Produced During Therapy in Responding Patients | 5 participants |