immune thrombocytopenia MedDRA version: 23.0 Level: LLT Classification code 10050245 Term: Autoimmune thrombocytopenia System Organ Class: 100000004851 MedDRA version: 22.1 Level: LLT Classification code 10036735 Term: Primary thrombocytopenia System Organ Class: 100000004851
Conditions
Interventions
Trade Name: Revolade
Product Name: Eltrombopag
Product Code: ETB115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ELTROMBOPAG
CAS Number: 496775-62-3
Current Sponsor code: ETB115
Other
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent must be obtained prior to participation in the study. 2. Men and women = 18 years of age 3. Newly diagnosed with primary ITP (time from diagnosis within 3 months). Platelet count =65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: 1. Previous history of treatment for ITP. Note: Patients in need of immediate treatment for thrombocytopenia while diagnosis or eligibility are being determined may receive treatment with any ITP-directed therapy for a maximum of 3 days within 7 days before randomization. These therapies must be discontinued before the patient receives the first dose of study treatment 2. Patients with diagnosis of secondary thrombocytopenia 3. Patients who have life threatening bleeding complications per physician´s discretion 4. Patients with a history of thromboembolic events in the 6 months preceding enrollment or known risk factors for thromboembolism (e.g. Factor V Leiden, ATIII deficiency, antiphospholipid syndrome) are excluded. Patients with other risk factors which may pose an increased thromboembolic event (TEE) risk (prolonged periods of immobilization, malignancies, contraceptives and hormone replacement therapy, surgery/trauma, obesity and smoking) would be excluded according to the discretion of the investigator. 5. Presence of moderate to severe impaired renal function as indicated by any or all of the following criteria: • Creatinine clearance 1.5 mg/dL 6. Total bilirubin (TBIL) > 1.5 × upper limit of normal (ULN) 7. Aspartate transaminase (AST) > 3.0 × ULN 8. Alanine transaminase (ALT) > 3.0 × ULN 9. Patients who are human immunodeficiency virus (HIV), HCV or hepatitis B surface antigen (HBsAg) positive 10. Patients with hepatic impairment (Child-Pugh score > 5) 11. Patients with known active or uncontrolled infections not responding to appropriate therapy 12. History of current diagnosis of cardiac disease or impaired cardiac function denoted by any of the following: • Corrected QTc >450 msec using Fridericia correction (QTcF) on the screening electrocardiogram (ECG) • History of myocardial infarction and unstable angina within 6 months prior to starting study treatment • Clinically significant cardiac arrhythmias or other clinically significant cardiovascular disease (e.g., congestive heart failure, uncontrolled hypertension) within the six months prior to starting study treatment 13. Patients who have active malignancy 14. Patients with evidence of current alcohol/drug abuse 15. Any serious and/or unstable pre-existing medical (including any advanced malignancy other than the disease under study), psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance with the study procedures. 16. Patients with a known immediate or delayed hypersensitivity reaction or idiosyncrasy to eltrombopag or drugs chemically related to eltrombopag or excipients that contraindicate their participation 17. Patients with pre-existing medical conditions that are known precautions with corticosteroid use, in whom the potential risks of participating in the study outweigh the potential benefits as determined by the investigator 18. Female subjects who are nursing or pregnant (positive serum or urine B-human chorionic gonadotrophin (B-hCG) pregnancy test) at screening or pre-dose on Day 1 19. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 7 days after stopping medication. Highly effective contraception methods include: • combined (estrogen and progestogen containi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the ability of eltrombopag in combination with a short course of dexamethasone to induce a sustained response off treatment at 52 weeks versus a defined course of dexamethasone ;Secondary Objective: 1. To compare ability of eltrombopag in combination with short course of dexamethasone to induce overall response after treatment discontinuation at Week 52 versus defined course of dexamethasone 2. To assess duration of sustained response off treatment 3. To assess ability of eltrombopag to induce overall response by Week 4 4. To assess ability of eltrombopag to induce complete Response by Week 4 5. To quantify increase in platelet count from screening to baseline and to 1, 2, 4, 12, 26 and 52 weeks 6. To assess time to overall and complete response 7. To assess duration of overall and complete response 8. To evaluate patient-oriented outcomes for health-related quality of life 9. To evaluate safety and tolerability of eltrombopag + dexamethasone 10. To evaluate incidence and severity of bleeding events ;Primary end point(s): The primary endpoint is the proportion of patients with sustained response off treatment at 52 weeks. Sustained response off treatment is defined as: • reach platelet count = 30×10^9/L and then maintain platelet counts = 30 × 10^9/L after treatment discontinuation AND • maintain platelet count = 30 × 10^9/L in the absence of bleeding events = Grade 2 and without the use of any rescue therapy at all visits until Week 52. ;Timepoint(s) of evaluation of this end point: at week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To compare the ability of eltrombopag in combination with a short course of high dose dexamethasone to induce overall response (OR) after treatment discontinuation at week 52 versus a defined course of dexamethasone Proportion (%) of patients with platelet count = 30×10^9/L and a 2-fold increase of screening platelet count after treatment discontinuation in the absence of bleeding events = Grade II and no rescue therapy at all visits until Week 52 will be provided, analysis will be equivalent to the primary endpoint analysis. 2. To assess the duration of sustained response off treatment, median duration of response off treatment (weeks) counted from last dose of study treatment (eltrombopag or dexamethasone) until loss of response will be calculated using a Kaplan-Meier analysis. 3. To assess the ability of eltrombopag to induce overall response (OR) by week 4 Number (%) of patients with platelet count = 30×10^9/L and a 2-fold increase of screening platelet count at least once within the first 4 weeks without bleeding events = Grade II and no rescue therapy will be provided, analysis will be equivalent to the primary endpoint analysis. 4. To assess the ability of eltrombopag to induce a complete response (CR) by week 4 Number (%) of patients with platelet count = 100×10^9/L at least once within the first 4 weeks without bleeding events = Grade II and no rescue therapy will be provided, analysis will be equivalent to the primary endpoint analysis. 5. To assess the platelet count from screening to baseline and to 1, 2, 4, 12, 26 and 52 weeks; absolute and relative change in platelet count from screening to baseline and to 1, 2, 4, 12, 26 and 52 weeks and EOS will be provided. Box plots for absolute and/or relative change in platelet counts from screening to baseline and to different time points will also be provided. 6. To assess the time to response for overall and complete response using a Kaplan Meier analysis. 7. To assess the duratio | — |
Countries
Germany
Contacts
Public ContactMedizinischer Infoservice
Novartis Pharma GmbH
Outcome results
None listed