Inherited thrombocytopenias MedDRA version: 17.0 Level: HLT Classification code 10043555 Term: Thrombocytopenias System Organ Class: 100000004851
Conditions
Interventions
Product Name: Eltrombopag 12.5 mg
Product Code: NA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ELTROMBOPAG OLAMINE
CAS Number: 496775-62-3
Other descriptive name: ELTROMBOPAG OLAMINE
Sponsors
Fondazione IRCCS Policlinico San Matteo
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase 1 Patients with the following forms of inherited thrombocytopenias will be considered for enrolment: - MYH9-related disorders (OMIM 155100, 605249, 153640, 153650) - Bernard-Soulier Syndrome (OMIM 231200) deriving from monoallelic mutations (at variance with biallelic classical BSS, monoallelic form does not present defective platelet function) - Wiskott-Aldrich syndrome (OMIM 301000). - X-linked thrombocytopenia (OMIM 313900). - X-linked thrombocytopenia with thalassemia (OMIM 314050). - Dyserythropoietic anemia with thrombocytopenia (OMIM 300367). - ITGA2B/ITGB3-related thrombocytopenia (OMIM not available). - ANKRD26-related thrombocytopenia (OMIM 188000). - TUBB1-related thrombocytopenia (OMIM not available) - ACTN1-related thrombocytopenia (OMIM not available) - GFI1B-related thrombocytopenia (OMIM not available) Patients will have to fulfill all the following criteria: - Age = 16 years and = 70 years - Average platelet count during the previous year less than 80 x109/L - Written informed consent Phase 2 Patients with clinically relevant chronic or recurrent bleedings at baseline (grade 2-4 of the WHO bleeding scale) who: (i) completed the phase 1 without severe side effects and (ii) obtained reduction or remission of bleeding by Eltrombopag administration. Are the trial subjects under 18? yes Number of subjects for this age range: 3 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: Phases 1 and 2 -Hypersensitivity to Eltrombopag or one of the excipients. - History of thromboembolic events. - Treatment with anti-platelet drugs or other drugs affecting platelet function and/or with anticoagulants. - Concurrent diseases or conditions that significantly increase the risk of thromboembolic events, including: malignancies, congestive heart failure (NYHA Grade III/IV), atrial fibrillation or other arrhythmias that predispose to thromboembolic events, known hereditary factors predisposing to venous thromboembolism (factor V mutations, factor II mutations, deficiency of antithrombin III, or protein C, or protein S), antiphospholipid syndrome, hormone replacement therapy and systemic contraception containing estrogen, severe obesity, severe hypertension not controlled by treatment, heavy smoking, diabetes mellitus not controlled by therapy or complicated, severe dislipidemia, haemoglobinopathies increasing the risk of thrombotic events, such as sickle cell anemia or thalassemia major. - Moderate to severe liver failure (Child-Pugh score = 5). - Altered renal function as defined by creatinine = 2 mg/dL - Previous or concurrent clonal disorders of the myeloid series (acute myeloid leukemias and myelodysplastic syndromes). - Females who are pregnant or nursing (a negative pregnancy test is required before enrolment of fertile women). - Formal refusal of any recommendations for a safe contraception. - Alcohol or drug addiction. - Any other disease or condition that by the advice of the responsible physician would make the treatment dangerous for the patient or would make the patient ineligible for this study, including physical, psychiatric, social and behavioral problems.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Dosages of eltrombopag required for achieving the primary endpoints of Phases 1 and 2. - Ability to receive the programmed treatment with eltrombopag without side effects requiring drug discontinuation Exploratory Endpoints: Effect of treatment on serum thrombopoietin (TPO) level, number of reticulated platelets, in vitro platelet aggregation. ;Timepoint(s) of evaluation of this end point: End of study | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 To ascertain whether and in which forms of inherited thrombocytopenia eltrombopag can be used to transiently increase platelet count over 100 x 109/L and to abolish bleeding tendency. Phase 2 To verify whether and in which forms of inherited thrombocytopenia eltrombopag can be used to stably reduce bleeding tendency in patients with clinical significant bleedings and who had their bleeding tendency reduced during Phase 1 of the study.;Secondary Objective: Phases 1 and 2 - Evaluate safety and tolerability of Eltrombopag in patients with inherited thrombocytopenias. - Identify the dosages of Eltrombopag required to obtain the primary objectives of Phases 1 and 2. ;Primary end point(s): Phase 1: Platelet counts higher than 100 x 109/L and no bleeding events (Grade 0 of WHO bleeding scale) during the last week of treatment. Phase 2: Long term reduction of bleeding tendency as measured by the WHO bleeding scale.;Timepoint(s) of evaluation of this end point: Phase 1: last week of treatment Phase 2: end of study | — |
Countries
Italy
Contacts
Public ContactMedicina Generale III
Fondazione IRCCS Policlinico San Matteo
Outcome results
None listed