A Clinical Trial of the Orelabrutinib in the Management of Refractory ITP

Study Overview
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Brief Summary
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BTK participates in a variety of signal transduction of innate and adaptive immunity, and has an important role in cell proliferation, differentiation and apoptosis. The impact of BTK inhibitors on hematological malignancies and autoimmune diseases has been well studied. This project was undertaking by Qilu Hospital of Shandong University in China. In order to report the efficacy and safety of the selective BTK inhibitor Orelabrutinib in the management of refractory ITP.

Detailed Description
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The investigators are undertaking a prospective, open-lable, multicentre trial of 40 refractory ITP adult patients in China. Eligible participants will receive Orelabrutinib in 50 mg po. qd, every 4 weeks for one cycle and it will be given 3 cycles. For non-responders who were well tolerated at 12 weeks of follow-up, the treatment could be extended to 6 cycles. The treatment will be discontinued after 6 months without blood index reaction. In order to report the efficacy and safety of Orelabrutinib in the management of refractory ITP, platelet count, bleeding and other symptoms will be evaluated before and after treatments. Adverse events are also recorded throughout the study.

Official Title
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A Prospective, Open-label, Multicenter，Single-armed Study of Orelabrutinib in the Treatment of Refractory Primary Immune Thrombocytopenia (ITP)

Conditions
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Immune Thrombocytopenia, Bruton's Tyrosine Kinase

Intervention / Treatment
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* Drug: Orelabrutinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the diagnostic criteria for primary immune thrombocytopenia To show a platelet count < 30 * 10^9/L, or with bleeding manifestations, or both Willing and able to sign written informed consent Meet the diagnostic criteria of refractory ITP according to Chinese guidelines Exclusion Criteria: Secondary thrombocytopenia severe immune-deficiency or history of primary immunodeficiency active or previous malignancy HIV virus infection, tuberculosis, or other active infection (sepsis, pneumonia, or abscess) pregnancy or lactation diabetes hypertension cardiovascular diseases severe liver or kidney function impairment psychosis osteoporosis inflammatory bowel disease or gastric disease arterial or venous thromboembolism within the 6 months before screening or patients who required anticoagulant treatment an organ or haematopoietic stem-cell transplantation neutrophil count of less than 1500 cells per mm³; glycosylated haemoglobin less than 8%; partial thromboplastin time 1∙5 times or less the upper limit of normal (ULN) clinical electrocardiogram changes neoplastic disease within the past 5 years corrected QT interval greater than 450 ms for men and greater than 470 ms for women; substance misuse within the previous 12 months; and those who could not adhere to the protocol or were planning to have a surgical procedure in 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Orelabrutinib<br>Orelabrutinib 50mg po qd | Drug: Orelabrutinib<br>* Orelabrutinib 50mg po qd, every four weeks for one cycle. It will be given three cycles.<br>* Other names: ICP-022;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial overall response to Orelabrutinib | Complete response was defined as a platelet count of 100×10⁹ cells per L or higher and an absence of bleeding. Partial response was defined as a platelet count of 30×10⁹ cells per L or higher, but less than 100×10⁹ cells per L, and at least a doubling of the baseline platelet count and an absence of bleeding. Platelet counts were confirmed on two separate occasions at least 7 days apart when defining complete response or partial response. No response was defined as a platelet count of less than 30×10⁹ cells per L, or less than two-times increase from baseline platelet count, or bleeding. | 14 days after the first dose of Orelabrutinib | 
| Sustained overall response to Orelabrutinib | Complete response was defined as a platelet count of 100×10⁹ cells per L or higher and an absence of bleeding. Partial response was defined as a platelet count of 30×10⁹ cells per L or higher, but less than 100×10⁹ cells per L, and at least a doubling of the baseline platelet count and an absence of bleeding. Platelet counts were confirmed on two separate occasions at least 7 days apart when defining complete response or partial response. No response was defined as a platelet count of less than 30×10⁹ cells per L, or less than two-times increase from baseline platelet count, or bleeding. | A response lasting for at least 6 months without any additional intervention specific to primary immune thrombocytopenia was defined as a sustained response | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to response | Time from treatment initiation to achieve a complete response or a partial response | An average of 6 months | 
| Duration of response | Time from achievement of a complete response or a partial response to the loss of response (platelet count <30×10⁹ cells per L; measured on two occasions more than 1 day apart or the presence of bleeding). | through study completion, an average of 1 year | 
| Therapy associated adverse events | Potential adverse events: leukopenia (report in number * 10^9/L, time of occurrence and duration); nausea and diarrhea (report in frequency); infection (report pathogens and infectious diseases). | Up to 1 year | 

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