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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Immune Thrombocytopenia; Bruton's Tyrosine Kinase
• Intervention / Treatment: Drug: Orelabrutinib

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ming Hou, MD,PhD; Phone Number: 0531-82169879; Email: houming@medmail.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Orelabrutinib; Orelabrutinib 50mg po qd	Drug: Orelabrutinib; Orelabrutinib 50mg po qd, every four weeks for one cycle. It will be given three cycles.; Other Names: ICP-022

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shandong University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 1, 2021
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): June 1, 2024

Study Registration Dates

• First Submitted: August 12, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (ACTUAL): August 25, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 25, 2021
• Last Update Submitted That Met QC Criteria: August 18, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Orelabrutinib
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
• Other Study ID Numbers: ITP-Orelabrutinib

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No