Thrombocytopenia in paediatric subjects with immune thrombocytopenia for =6 months duration who have had an insufficient response to a previous treatment MedDRA version: 20.0 Level: HLT Classification code 10043555 Term: Thrombocytopenias System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 23.0 Level: LLT Classification code 10083843 Term: Primary immune thrombocytopenia System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 23.0 Le
Conditions
Interventions
Trade Name: Doptelet 20 mg film-coated tablets
Product Name: avatrombopag
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Avatrombopag maleate
CAS Number: 677007-74-8
Current Sponsor code
Sponsors
Sobi, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For the CORE phase: 1. Male or female subjects =1 and 35×109/L. The platelet count obtained at the Screening Visit/Visit 1 and 1 other platelet count taken within 28 days on either side of the Screening Visit (may use a historical value collected per standard of care if within 28 days of Screening) will be averaged to obtain the study eligibility platelet count value, which must be <30×109/L. The 2 samples must be obtained =24 hours and =28 days apart and the results must be available prior to randomization. 5. Subjects being treated chronically with corticosteroids or azathioprine/6-mercaptopurine must be receiving a stable dose for at least 30 days prior to Day 1/Visit 2 or must have completed these therapies more than 30 days prior to Day 1/Visit 2. 6. Subjects being treated with mycophenolate mofetil (MMF), cyclosporine (CsA), sirolimus, or danazol must be receiving a stable dose for at least 90 days prior to Day 1/Visit 2 or must have completed these therapies more than 30 days prior to Day 1/Visit 2. 7. Previous therapy for ITP with immunoglobulins (IVIg and anti-D) or corticosteroid rescue therapy must have been completed at least 14 days prior to Day 1/Visit 2. 8. Cyclophosphamide and vinca alkaloid regimens must have been completed at least 30 days prior to Day 1/Visit 2. 9. Splenectomy and rituximab must have been completed at least 90 days prior to Day 1/ Visit 2. 10. Previous therapy with any other TPO-RAs (e.g., eltrombopag or romiplostim) or recombinant human TPO must have been completed 28 days prior to Day 1/Visit 2. 11. Previous therapy with vitamin K antagonists, antifibrinolytic agents, recombinant activated factor VII, heparin, factor Xa inhibitors, direct thrombin inhibitors, desmopressin, or chronic antiplatelet therapy must have been completed within 7 days of Day 1/Visit 2. 12. Previous therapy with moderate or strong dual inducers or moderate or strong dual inhibitors of cytochrome P450 (CYP)2C9 and CYP3A4 must have been completed within 7 days of Day1/Visit 2. 13. Platelet transfusion, or receipt of blood products containing platelets must have been completed within 7 days of Day 1/Visit 2. Packed red blood cells (RBCs) are permitted. 14. Females of childbearing potential must have a negative urine or serum pregnancy test at Screening and Day 1/Visit 2 and must not be breastfeeding. 15. Female subjects of childbearing potential and who are sexually active and male subjects who are sexually active must agree to use highly effective methods of contraception. 16. Subject and/or subject’s LAR is willing and able to comply with all aspects of the protocol. For the EXTENSION phase: 1. Subject and/or the LAR must provide consent and/or assent, as applicable, to continue into the open-label Extension Phase. The consent for the Extension Phase will be part of the consent for the Core Phase. 2. Completed 12 weeks of treatment in the Core Phas
Exclusion criteria
Exclusion criteria: For the CORE phase: 1. Known secondary ITP. 2. Body Mass Index (BMI) >30 kg/m2 or >95% for age. 3. Any history of arterial or venous thrombosis, including partial or complete thrombosis. 4. Subjects with known inherited thrombocytopenia (e.g., MYH-9 disorders). 5. History of myelodysplastic syndrome (MDS). 6. Known history of congenital heart abnormalities or arrhythmias. 7. History of hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV). 8. Known history of disseminated intravascular coagulation (DIC), hemolytic uremic syndrome (HUS), or thrombotic thrombocytopenic purpura (TTP). 9. Subjects with Evans syndrome. 10. Concurrent malignant disease or previous history of myeloid hematologic malignancies. 11. Hemoglobin (Hgb) levels =9 g/dL in ages =1 year to 1.5× the upper limit of normal (ULN) for age, alanine transaminase (ALT) and aspartate aminotransferase (AST) >3× the ULN for age. 14. Known allergy to avatrombopag or any of its excipients. 15. Subject is unable to take oral medication or has a malabsorption syndrome, or has known hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption or any other uncontrolled gastrointestinal condition. 16. Enrollment in another clinical study with any investigational drug or device within 30 days of Day 1/Visit 2 (or 5 half-lives, whichever is longer); however, participation in observational studies within the previous 30 days is permitted. 17. Any clinically relevant abnormality which makes the subject unsuitable for participation in the study, in the opinion of the Investigator. 18. Considered unable or unwilling to comply with the study protocol requirements. For the EXTENSION phase: 1. Significant safety or tolerability concerns with the subject’s participation, in the opinion of the Investigator. 2. Subjects requiring the following drugs or procedures at the time of enrollment into the Extension Phase: • Rituximab • Other TPO-RAs • Splenectomy • Moderate or strong dual inducers or moderate or strong dual inhibitors of CYP2C9 and CYP3A4.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that the efficacy of avatrombopag is superior to placebo for the treatment of pediatric subjects with ITP of =6 months duration who have had an insufficient response to a previous treatment;Secondary Objective: • To evaluate the safety and tolerability of avatrombopag • To evaluate the PK and PD of avatrombopag;Primary end point(s): Primary Efficacy Endpoint: Durable platelet response as defined by the proportion of subjects achieving at least 6 out of 8 weekly platelet counts =50×109/L during the last 8 weeks of the 12 week Treatment Period in the Core Phase in the absence of rescue medication. Alternative Primary Efficacy Endpoint: Platelet response as defined by the proportion of subjects for whom at least 2 consecutive platelet assessments are =50×109/L over the 12 week Treatment Period in the Core Phase in the absence of rescue medication.;Timepoint(s) of evaluation of this end point: After 12 week Treatment Period in the Core Phase | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The percentage of weeks subjects have a platelet count =50×109/L during 12 weeks of treatment in the Core Phase, in the absence of rescue therapy. • Platelet response at Day 8 (defined by the proportion of subjects with a platelet count =50×109/L at Day 8, in the absence of rescue therapy). • The percentage of weeks subjects have a platelet count between =50×109/L and =150×109/L, during 12 weeks of treatment in the Core Phase, in the absence of rescue therapy. • The proportion of subjects who require rescue medications during 12 weeks of treatment in the Core Phase of the study. • Incidence and severity of bleeding symptoms associated with ITP measured using the WHO Bleeding Scale. ;Timepoint(s) of evaluation of this end point: After 12 week Treatment Period in the Core Phase | — |
Countries
France, Germany, Hungary, Poland, Russian Federation, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactMedical Information
Sobi, Inc.
Outcome results
None listed