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

Immune Thrombocytopenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05020288
• Other study ID #: ITP-Orelabrutinib
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 1, 2021
• Est. completion date: June 1, 2024

Study information

• Verified date: August 2021
• Source: Shandong University
• Contact: Ming Hou, MD,PhD
• Phone: 0531-82169879
• Email: houming[@]medmail.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: June 1, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Immune Thrombocytopenia
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Drug:
• Orelabrutinib
Orelabrutinib 50mg po qd, every four weeks for one cycle. It will be given three cycles.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Shandong University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Initial overall response to Orelabrutinib	Complete response was defined as a platelet count of 100×10? cells per L or higher and an absence of bleeding. Partial response was defined as a platelet count of 30×10? cells per L or higher, but less than 100×10? 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 30×10? cells per L, or less than two-times increase from baseline platelet count, or bleeding.	14 days after the first dose of Orelabrutinib
Primary	Sustained overall response to Orelabrutinib	Complete response was defined as a platelet count of 100×10? cells per L or higher and an absence of bleeding. Partial response was defined as a platelet count of 30×10? cells per L or higher, but less than 100×10? 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 30×10? 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	Time to response	Time from treatment initiation to achieve a complete response or a partial response	An average of 6 months
Secondary	Duration of response	Time from achievement of a complete response or a partial response to the loss of response (platelet count <30×10? 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
Secondary	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