Evaluation of Avatrombopag for the Treatment of Thrombocytopenia in Japanese Adults With Chronic ITP

Study Overview
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Brief Summary
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Evaluate the efficacy, safety, and PK of avatrombopag given for 26 weeks in Japanese adults with chronic immune thrombocytopenia (ITP).

Detailed Description
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This Phase 3, multicenter, open label study will evaluate the efficacy, safety, and population pharmacokinetics (PK) of avatrombopag in Japanese adults with chronic ITP. At least 19 subjects will be enrolled. The study will consist of 3 phases: Pre-enrollment, Primary Investigation, and Extension Phase until market authorization in Japan.

Official Title
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An Open-label Study to Evaluate the Efficacy and Safety of Avatrombopag for the Treatment of Thrombocytopenia in Japanese Adults With Chronic Immune Thrombocytopenia

Conditions
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Immune Thrombocytopenia

Intervention / Treatment
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* Drug: Avatrombopag Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has a confirmed diagnosis of chronic immune thrombocytopenia (ITP) (≥12 months duration) and has had an insufficient response to a previous ITP treatment, in the opinion of the Investigator. Subject has an average of 2 platelet counts <30×10^9/L (no single count can be >35×10^9/L). The 2 samples must be obtained ≥48 hours and ≤2 weeks apart. Exclusion Criteria: 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). Subjects with known inherited thrombocytopenia (e.g., Myosin Heavy Chain 9 (MYH-9) disorders) or hereditary thrombophilic disorders (e.g., Factor V Leiden, antithrombin III deficiency). History of myelodysplastic syndrome (MDS). History of arterial or venous thrombosis. 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], angina, coronary artery stent placement, angioplasty, coronary artery bypass grafting). Subjects with a history of cirrhosis, portal hypertension, or chronic active hepatitis. Subjects with concurrent malignant disease or receiving cytotoxic chemotherapy for a reason other than ITP treatment. Use of immunoglobulins (IVIg and anti-D) or corticosteroid rescue therapy within 1 week of Day 1/Baseline. Splenectomy or use of rituximab within 12 weeks of Day 1/Baseline. Use of romiplostim or eltrombopag within 1 week of Day 1/Baseline. Use of chronic corticosteroid treatment or azathioprine within 4 weeks of Day 1/Baseline, unless receiving a stable dose for at least 4 weeks. Use of mycophenolate mofetil, cyclosporin A, or danazol within 4 weeks of Day 1/Baseline, unless receiving a stable dose for at least 12 weeks. Use of cyclophosphamide or vinca alkaloid regimens within 4 weeks of Baseline Visit. Currently receiving moderate or strong dual inhibitors/inducers of CYP2C9 and CYP3A4. Serum creatinine ≥1.5× the upper limit of normal (ULN). Serum bilirubin ≥2×ULN. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3×ULN. Females who are pregnant (positive beta-human chorionic gonadotropin (β-hCG) test) or breastfeeding. Received treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) before Day 1/Baseline.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Avatrombopag<br>Avatrombopag 20 mg oral tablet | Drug: Avatrombopag Oral Tablet<br>* Avatrombopag 20 mg given once daily (initial dose). Dose adjustments will be determined by the physician and in accordance with the overseas Doptelet prescribing information.<br>* Other names: Doptelet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Number of Weeks of Platelet Response | Cumulative number of weeks in which the platelet count is ≥50×10^9/L during 26 weeks of treatment in the absence of rescue therapy. | 26 weeks of active treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate at Day 8 | Proportion of subjects with a platelet response ≥50×10^9/L at Day 8 in the absence of rescue therapy | Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ITP