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

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) - Not applicable

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2011-000830-12-NL

Enrollment

Registered

2011-08-23

Start date

2012-08-28

Completion date

Unknown

Last updated

2018-01-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Immune Thrombocytopenia (Idiopathic Thrombocytopenic Purpura) MedDRA version: 16.1 Level: HLGT Classification code 10035534 Term: Platelet disorders System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 16.1 Level: PT Classification code 10043554 Term: Thrombocytopenia System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 16.1 Level: LLT Classification code 10036735 Term: Primary thrombocytopenia System Organ Class: 1000532

Interventions

Product Name: E5501 Product Code: E5501 Pharmaceutical Form: Film-coated tablet INN or Proposed INN: Avatrombopag (proposed) CAS Number: 1254322-84-3 Current Sponsor code: E5501 Other descriptive name

Eligibility

Sex/Gender

All

Inclusion criteria

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 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 (excluding platelet count), within the reference range (with white blood count [WBC] differential not indicative of any significant hematological disorder), 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 Dsicontinuation) 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 43 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6

Exclusion criteria

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 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 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 01) 21. Alanine aminotransferase (ALT) OR aspartate aminotrans

Design outcomes

Primary

Measure	Time frame
Timepoint(s) of evaluation of this end point: During 6 months of treatment (i.e., at Visit 3 to 22 inclusive).;Main Objective: Core Study To demonstrate that the efficacy of E5501 (in addition to standard of care) is superior to placebo (in addition to standard of care) for the treatment of adult subjects with chronic immune thrombocytopenia (idiopathic thrombocytopenic purpura) (ITP) as measured by durable platelet response Extension Phase To evaluate the safety and tolerability of long-term therapy with E5501 in subjects with chronic ITP (cITP);Secondary Objective: Core Study • To demonstrate that the efficacy of E5501 (in addition to standard of care) is superior to the efficacy of placebo (in addition to standard of care) as measured by platelet response rate at Day 8 • To demonstrate that the efficacy of E5501 (in addition to standard of care) is superior to the efficacy of placebo (in addition to standard of care) as measured by the proportion of subjects with reduction in concomitant ITP medication use • To evaluate the safety of E5501 compared with placebo Extension Phase • To demonstrate the effectiveness of long-term therapy with E5501 as measured by platelet response, bleeding, and the use of rescue therapy • To assess the reduction in use of steroids and concomitant ITP medication in subjects receving E5501;Primary end point(s): Core Study Proportion of subjects who have at least 6 of 8 (i.e., = 75%) weekly platelet responses during the last 8 weeks of treatment (ie, at Visit 15 to 22 inclusive) over the 6-month treatment period in the absence of rescue therapy. Subjects using rescue therapy at any time during the 6 month treatment period will be considered not to have a durable platelet response. A platelet response will be defined as a platelet count of = 50 x 109/L and nonresponse will be defined as a platelet count < 50 x 109/L. Missing platelet assessments at any given time point will be considered to be a nonresponse at that time point. Sub	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: During 6 months of treatment (i.e., at Visit 3 to 22 inclusive).;Main Objective: Core Study To demonstrate that the efficacy of E5501 (in addition to standard of care) is superior to placebo (in addition to standard of care) for the treatment of adult subjects with chronic immune thrombocytopenia (idiopathic thrombocytopenic purpura) (ITP) as measured by durable platelet response Extension Phase To evaluate the safety and tolerability of long-term therapy with E5501 in subjects with chronic ITP (cITP);Secondary Objective: Core Study • To demonstrate that the efficacy of E5501 (in addition to standard of care) is superior to the efficacy of placebo (in addition to standard of care) as measured by platelet response rate at Day 8 • To demonstrate that the efficacy of E5501 (in addition to standard of care) is superior to the efficacy of placebo (in addition to standard of care) as measured by the proportion of subjects with reduction in concomitant ITP medication use • To evaluate the safety of E5501 compared with placebo Extension Phase • To demonstrate the effectiveness of long-term therapy with E5501 as measured by platelet response, bleeding, and the use of rescue therapy • To assess the reduction in use of steroids and concomitant ITP medication in subjects receving E5501;Primary end point(s): Core Study Proportion of subjects who have at least 6 of 8 (i.e., = 75%) weekly platelet responses during the last 8 weeks of treatment (ie, at Visit 15 to 22 inclusive) over the 6-month treatment period in the absence of rescue therapy. Subjects using rescue therapy at any time during the 6 month treatment period will be considered not to have a durable platelet response. A platelet response will be defined as a platelet count of = 50 x 109/L and nonresponse will be defined as a platelet count < 50 x 109/L. Missing platelet assessments at any given time point will be considered to be a nonresponse at that time point. Sub

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Secondary

Measure	Time frame
Timepoint(s) of evaluation of this end point: • Day 8 • From the time of first response over a 6- month treatment period (in the absence of rescue therapy).;Secondary end point(s): • Platelet response rate at Day 8 (as defined by the proportion of subjects with a platelet response =50 x 109/L at Day 8). Subjects with missing platelet counts at Day 8 or use of a rescue therapy before or on Day 8, will be considered platelet nonresponders. • Proportion of subjects with a reduction in use of concomitant ITP medications from baseline	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: • Day 8 • From the time of first response over a 6- month treatment period (in the absence of rescue therapy).;Secondary end point(s): • Platelet response rate at Day 8 (as defined by the proportion of subjects with a platelet response =50 x 109/L at Day 8). Subjects with missing platelet counts at Day 8 or use of a rescue therapy before or on Day 8, will be considered platelet nonresponders. • Proportion of subjects with a reduction in use of concomitant ITP medications from baseline

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Countries

Australia, Belgium, Bulgaria, Czech Republic, Greece, Netherlands, New Zealand, Poland, Singapore, Slovakia, South Africa, Ukraine

Contacts

Public ContactMedical Information

Eisai Limited

LmedInfo@eisai.net+4408456761400

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026