A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial with an Open-label Extension Phase to Evaluate the Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults with Chronic Immune Thrombocytopenia (Idiopathic Thrombocytopenic Purpura).

Phase 3

Withdrawn

Conditions: chronic immune thrombocytopenia
ITP
10035534
10003816

Registration Number: NL-OMON37708

Lead Sponsor: Eisai

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 2

Inclusion Criteria

Core Study:
1. Men and women >= 18 years of age
2. Subjects diagnosed with cITP (>=12 months duration) according to the American Society for Hematology/British Committee for Standards in Hematology (ASH/BCSH) guidelines, and an average of two platelet counts < 30 × 109/L (no single count may be >35 × 109/L). In addition, a peripheral blood smear should support the diagnosis of ITP with no evidence of other causes of thrombocytopenia (e.g.,
pseudothrombocytopenia, myelofibrosis). The physical examination should not suggest any disease which may cause thrombocytopenia other than ITP
3. Subjects who previously received one or more prior ITP therapies (including, but are not limited to corticosteroids, immunoglobulins, azathioprine, danazol, cyclophosphamide and/or rituximab).
4. Subjects must have had either initially responded (platelet count >50 × 109/L) to a previous ITP therapy or have had a bone marrow examination consistent with ITP within 3 years to rule out
myelodysplastic syndrome (MDS) or other causes of thrombocytopenia.
5. Prothrombin time/International Normalized Ratio and activated partial thromboplastin time must have been within 80% to 120% of the normal range with no history of hypercoagulable state.
6. A complete blood count, within the reference range (including white blood count [WBC] differential not indicative of a disorder other than ITP), with the following exceptions:
• Hemoglobin: Subjects with hemoglobin levels between 10 g/dL (100 g/L) and the lower limit of normal (LLN) are eligible for inclusion, if anemia is clearly attributable to ITP (excessive blood loss).
• Absolute neutrophil count (ANC) >= 1500/µL (1.5 x 109/L) was required for inclusion (elevated WBC/ANC due to corticosteroid treatment is acceptable).
• Elevated WBC or ANC (e.g., due to corticosteroid treatment) provided this is discussed with the medical monitor;Extension Phase:
1. Subjects who have completed 6 months of study treatment in the Randomization Phase or
2. Subjects who discontinue the Core Study early due to lack of treatment effects. (see Study Drug Discontinuation)
3. No significant safety or tolerability concerns with the subject*s participation of Randomization Phase as determined by the investigator.

Exclusion Criteria

Core Study:
1. Subjects with known secondary immune thrombocytopenia (e.g., with known Helicobacter pylori-induced ITP, subjects infected with known human immunodeficiency virus [HIV] or hepatitis C virus [HCV] or subjects with known systemic lupus erythematosus).
2. Subjects with significant medical conditions that may impact on the safety of the subject or interpretation of the study results (e.g., acute hepatitis, active chronic hepatitis; lymphoproliferative disease; myeloproliferative disorders, leukemia).
3. History of MDS.
4. History of gastric atrophy
5. History of pernicious anemia or subjects with vitamin B12 deficiency
(defined as cause
6. Any prior history of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism), and more than two of the following risk factors: hormone replacement therapy, estrogen-containing hormone replacement or contraceptive therapies, smoking, diabetes, hypercholesterolemia, medication for hypertension, cancer, hereditary thrombophilic disorders (e.g., Factor V Leiden, antithrombin III deficiency, etc.), or any other
family history of arterial or venous thrombosis.
7. Subjects with a history of significant cardiovascular disease (e.g., congestive heart failure [CHF] New York Heart Association Grade III/IV), arrhythmia known to increase the risk of thromboembolic
events (e.g., atrial fibrillation), subjects with a QT corrected for heart rate of > 450 msec, angina, coronary artery stent placement, angioplasty, coronary artery bypass grafting)
8. Subjects with a history of cirrhosis, portal hypertension, and chronic active hepatitis
9. Subjects with concurrent malignant disease
10. Use of immunoglobulins (IVIg and anti-D) within 1 week of randomization
11. Splenectomy or use of rituximab within 12 weeks of randomization
12. Use of romiplostim or eltrombopag within 4 weeks of randomization
13. Subjects who are currently treated with corticosteroids or azathioprine but have not been receiving a stable dose for at least 4 weeks prior to randomization or have not completed these therapies more than 4 weeks prior to randomization
14. Subjects who are currently treated with MMF, CsA, or danazol but have not been receiving a stable dose for at least 12 weeks prior to randomization or have not completed these therapies more than 4 weeks prior to randomization
15. Use of cyclophosphamide or vinca alkaloid regimens within 4 weeks of randomization.
16. Subjects who are currently treated with proton pump inhibitors (PPIs) or H2 antagonist therapy but have not been receiving a stable dose for at least 6 weeks prior to randomization or have not completed these therapies more than 2 weeks prior to randomization
17. Fasting gastrin-17 blood levels exceeding the upper limit of normal
(ULN) at Screening for subjects not on PPIs or H2 antagonists
18. Fasting gastrin-17 blood levels exceeding 1.5 times the ULN at Screening for subjects on PPIs or H2 antagonists.
19. Blood creatinine exceeding ULN by more than 20% OR total albumin exceeding the lower limit (LLN) of normal by 10%.
20. Alanine aminotransferase (ALT) OR aspartate aminotransferase (AST) levels exceeding 3 times the ULN OR total bilirubin exceeding 2 times the ULN.
21. Subjects with a history of cancer treatment with cytotoxic c