A Study on the Effect of E5501 (study drug) in Adults with Chronic Immune Thrombocytopenia

Phase 1

• Conditions: Chronic Immune Thrombocytopenia (Idiopathic Thrombocytopenic Purpura); MedDRA version: 14.1Level: HLGTClassification code 10035534Term: Platelet disordersSystem Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 14.1Level: PTClassification code 10043554Term: ThrombocytopeniaSystem Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 14.1Level: LLTClassification code 10036735Term: Primary thrombocytopeniaSystem Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 14.1Level: SOCClassification code 10005329Term: Blood and lymphatic system disordersSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2011-000830-12-BE
• Lead Sponsor: Eisai Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-09-20
• Last Update Posted: 12 March 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

Core Study
1. Men and women = 18 years of age
2. Subjects diagnosed with cITP (=12 months duration) according to the ASH/BCSH guidelines, with 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 ITP therapies (including but not limited to corticosteroids, immunoglobulins, azathioprine, danazol, cyclophosphamide, and/or rituximab).
4. Subjects must have 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 (revised per Amendment 01)

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

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)(Revised per Amendment 01)
2. Subjects considered unable or unwilling to comply with the study protocol requirements or give informed consent, as determined by the investigator
3. 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).
4. History of MDS.
5. History of gastric atrophy (added per Amendment 01)
6. History of pernicious anemia or subjects with vitamin B12 deficiency (defined as 7. 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.
8. 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)
9. Subjects with a history of cirrhosis, portal hypertension, and chronic
active hepatitis
10. Subjects with concurrent malignant disease
11. Use of immunoglobulins (IVIg and anti-D) within 1 week of
randomization
12. Splenectomy or use of rituximab within 12 weeks of randomization
13. Use of romiplostim or eltrombopag within 4 weeks of randomization
14. 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
15. 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
16. Use of cyclophosphamide or vinca alkaloid regimens within 4 weeks of randomization.
17. 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
18. Fasting gastrin-17 blood levels exceeding the upper limit of normal (ULN) at Screening for subjects not on PPIs or H2 antagonists (revised per Amendment 01)
19. Fasting gastrin-17 blood levels exceeding 1.5 times the ULN at Screening for subjects on PPIs or H2 antagonists (added per Amendment 01)
20. Blood creatinine exceeding ULN by more than 20% OR total albumin below the lower limit (LLN) of normal by 10% (revised per Amendment

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified