to Evaluate the Efficacy and Safety of Eltrombopag for Immune Thrombocytopenia With Chronic HBV Infection

Study Overview
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Brief Summary
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Primary Objective: To evaluate the efficacy of 6-week Eltrombopag to treat immune thrombocytopenia with chronic hepatitis B virus infection. Secondary Objective: To evaluate the efficacy and safety of 6-week and 22-week Eltrombopag to treat immune thrombocytopenia with chronic hepatitis B virus infection.

Detailed Description
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This is a single-arm phase II study to evaluate the efficacy and safety of Eltrombopag to treat immune thrombocytopenia with chronic hepatitis B virus infection. This study includes two stages. In Stage 1 (Week 1 to Week 6), the short-term efficacy, safety and tolerability of Eltrombopag is evaluated. At the end of Stage 1, the subjects who can benefit from Eltrombopag treatment (platelet count ≥30×109/L at least once and a 2-fold increase from baseline platelet count without rescue therapy, with no bleeding) can enter a 16-week prolonged stage (Stage 2) to evaluate longer-term efficacy and safety. The starting dose of Eltrombopag is 25 mg once daily, and the dose may be increased by 25 mg once daily according to protocol if the desired platelet response (>50×109/L) is not achieved. The daily dose should not exceed 75 mg. In Stage 1, weekly visits are required during the first 6 weeks of the study. In Stage 2, platelet counts will be obtained weekly during dose adjustment and every 4 weeks following establishment of a stable dose of Eltrombopag (stable dose is defined as the dose which remains unchanged for at least 2 weeks).

Official Title
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A Multicenter Single-arm Study to Evaluate the Efficacy and Safety of Eltrombopag for Immune Thrombocytopenia in Chinese Patients With Chronic HBV Infection

Conditions
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Thrombocytopenia Purpura, Chronic HBV Infection

Intervention / Treatment
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* Drug: Eltrombopag


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent. Subject is ≥18 years old. Diagnosis of HBV-infection duration for at least 6 months prior to the study and have a platelet count of <30 ×109/L on Day 1 (or within 48 hours prior to dosing on Day 1). Complete blood count results: white blood cells, absolute neutrophils count and hemoglobin are within the laboratory normal range, but abnormalities caused by HBV infection can be accepted. Subject is practicing an acceptable method of contraception. Women of childbearing potential must have a negative serum pregnancy test in the whole study. Exclusion Criteria: Liver cirrhosis (LC) defined as any of the following: Any symptom or sign typical of hepatic decompensation: including but not limited to ascites, splenomegaly, dilation of periumbilical collateral veins, hepatic encephalopathy Child-Pugh class B to C Biopsies are not required either for confirmation or for exclusion of LC, considering the high bleeding risk in these patients. Positive serology for HIV, hepatitis C virus (HCV), and/or hepatitis D virus (HDV). Pregnancy or lactation period. History of alcohol/drug abuse or dependence within 12 months of the study. History of thrombosis. The serum chemistry results exceed the upper laboratory normal range by more than 20%; except AST, ALT, GGT, ALP of CTCAE grade 1. Bone marrow examination conducted within 4 weeks prior to first dose reported an abnormal result, which in the opinion of the investigator makes the subject unsuitable for participation in the study. Pre-existing cardiac disease, including congestive heart failure of New York Heart Association [NYHA] Grade III/IV, arrhythmia requiring treatment or myocardial infarction within the last 6 months. No arrhythmia known to increase the risk of thrombotic events (e.g. atrial fibrillation), or patients with a QT >450msec or QTc > 480 for patients with a Bundle Branch Block. Subject has consumed aspirin, aspirin-containing compounds, salicylates, anticoagulants, quinine or non-steroidal anti-inflammatories (NSAIDs) for >3 consecutive days within 2 weeks prior to the study start and until the end of the study. Non-compliant patient Reluctance to take effective contraceptive measures during the trial History of solid organ or bone marrow transplant.

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 |
| --- | --- |
| Experimental: Eltrombopag<br>58 enrolled patients are picked up to take eltrombopag at the indicated dose. | Drug: Eltrombopag<br>* subjects will initiate treatment with 25 mg eltrombopag. Platelet counts is obtained weekly and dose adjustment should be done according to platelet counts. and maximum dose should not exceed 75 mg daily. Subjects whose platelet count between 50 150×109/L，the eltrombopag dose Maintain. platelet count between 150 250×109/L, need to reduce the dose of eltrombopag to the next lower dose or lower frequency. Subjects whose platelet count exceeds 250×109/L at any point during the treatment period, must have eltrombopag interrupted and increase the frequency of platelet monitoring to twice weekly, until platelet counts fall below 100×109/L.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with a platelet count ≥ 50×109/L at Day 43 | The proportion of subjects with a platelet count ≥ 50×109/L at Day 43 after the first 6 weeks of Eltrombopag treatment (Stage 1) | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate of treatment | Response rate including: a) the proportion of subjects achieving platelet counts ≥ 50×109/L at least once during the first 6 weeks (stage 1); b) the proportion of subjects whose platelet counts ≥ 30×109/L and at least two times of baseline platelet count at least once during the treatment. | 22 weeks | 
| Bleeding in two stages | according to the WHO bleeding grades to estimate the incidence and severity of bleeding symptoms during the treatment. | 22 weeks | 
| The duration time with Platelet count ≥ 50×109/L | Total duration of time a subject had a platelet count ≥ 50×109/L during treatment. | 22 weeks |