A Randomized Trial Comparing Optimized rhTPO Treatment With Eltrombopag Treatment in Pre-treated ITP Pts

Study Overview
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Brief Summary
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TE-ITP study: Compare the efficacy and safety of optimized rhTPO treatment versus Eltrombopag treatment in previously treated primary immune thrombocytopenia patients.

Detailed Description
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A multicenter randomized open-label trial to compare the efficacy and safety of an optimized rhTPO treatment versus Eltrombopag treatment in previously treated primary immune thrombocytopenia. Total treatment duration is 6 weeks, the primary endpoint is median time to achieve platelet count ≥50x10^9/L during 6 weeks observation.

Official Title
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Comparing the Efficacy and Safety of Optimized rhTPO Treatment Versus Eltrombopag Treatment in Previously Treated Primary Immune Thrombocytopenia Patients: A Multicenter Randomized Open-label Trial

Conditions
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Previously Treated Primary Immune Thrombocytopenia

Intervention / Treatment
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* Drug: rhTPO
* Drug: Eltrombopag


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is ≥18 years old. Disease duration is ≥3 months, diagnosed and treated as ITP prior to screening. Baseline platelet count <30×10^9/L. Subjects treated with maintenance corticosteroids or immunosuppressive therapy must be receiving a dose that has been stable for at least 1 month. Informed consent has been signed. Exclusion Criteria: Classified as refractory ITP. Subjects with any prior history of arterial or venous thrombosis, or thrombophilia in recent 1 year. Subjects who have previously received any platelet increasing drug such as rhTPO, thrombopoietin receptor agonist(TPO-RA), etc. within 30 days. Subjects who are known nonresponders to rhTPO or TPO-RA therapy. Subjects with positive hepatitis C virus antibody or human immunodeficiency virus(HIV) antibody, positive HBsAg and serum levels of hepatitis B virus (HBV) DNA >1000cps/ml. TBil or Scr> 1.5 x upper limit of normal (ULN), ALT or AST> 3.0 x ULN in recently 2 weeks. Subjects with any prior history of tumor. Female subjects who are nursing or pregnant. Any situation that investigate consider not suitable for pts to join the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Optimized rhTPO treatment<br>The study in a 2:1 randomization ratio (117 subjects to rhTPO group). | Drug: rhTPO<br>* initial therapy: rhTPO s.c, 300 or 600U/kg daily based on baseline platelet count; maintenance therapy: rhTPO s.c, 300   600U/kg every other day depends on platelet count.<br>* Other names: TPIAO;|
| Active Comparator: Eltrombopag treatment<br>The study in a 2:1 randomization ratio (58 subjects to Eltrombopag group). | Drug: Eltrombopag<br>* initial therapy: Eltrombopag oral, 25 or 50mg daily based on baseline platelet count; maintenance therapy: Eltrombopag oral, 25   75mg daily or every other day depends on platelet count.<br>* Other names: Eltrombopag olamine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median time to achieve platelet count ≥50x10^9/L during 6 weeks observation | Time from the start of treatment to the first time of achieving a platelet count ≥50x10^9/L without salvage therapy during the first 6 weeks. | in 6 weeks treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early response | Early response is defined as platelet count ≥ 30×10^9/L and at least doubling baseline at 1 week. | after 1 week treatment | 
| Initial response | Initial response is defined as platelet count ≥ 30×10^9/L and at least doubling baseline at 1 month. | after 1 month treatment | 
| 6 weeks response | 6 weeks response is defined as platelet count ≥ 30×10^9/L and at least doubling baseline at 6 weeks. | after 6 weeks treatment | 
| 3 months response | 3 months response is defined as platelet count ≥ 30×10^9/L and at least doubling baseline at 3 months. | after 3 months treatment | 
| Durable response | Durable response is defined as platelet count ≥ 30×10^9/L and at least doubling baseline at 6 months. | after 6 months treatment | 
| Time to treatment failure | Treatment failure is defined as: a platelet count ≤ 20 x 109/L for 4 consecutive weeks at the highest dose and schedule ; or, a major bleeding event; or, a change in therapy due to an intolerable side effect or bleeding symptoms (including a minor bleeding event). | in 6 weeks treatment | 
| Incidence of adverse events | treatment-related adverse events. | from study start date to the end of follow-up, up to 6 weeks | 
| Number of subjects with dosage under 600U/kg of rhTPO adverse events as assessed by CTCAE v5.0 | Number of subjects with dosage under 600U/kg of rhTPO adverse events as assessed by CTCAE v5.0 | from study start date to the end of follow-up, up to 6 weeks | 
| Number of subjects who develop anti-rhTPO antibodies | Number of subjects who develop anti-rhTPO antibodies | from study start date to the end of follow-up, up to 6 weeks | 
| The duration time with platelet count ≥50x10^9/L | Total duration of time a subject had platelet count ≥50x10^9/L during treatment | in 6 weeks treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rhTPO, Eltrombopag, Pre-treated, Primary Immune Thrombocytopenia