A Prospective, One-arm and Open Clinical Study of Zanubrutinib in the Treatment of Immune Thrombocytopenia

Safety and Efficacy of Zanubrutinib in the Treatment of Immune Thrombocytopenia

To evaluate the safety and efficacy of zanubrutinib in the treatment of immune thrombocytopenia in 30 patients.

Study Overview

• Status: Recruiting
• Conditions: Immune Thrombocytopenia; Treatment
• Intervention / Treatment: Drug: Zanubrutinib

Detailed Description

Immune thrombocytopenia (ITP) is an organ-specific autoimmune disease, which is characterized by decreased platelet count and skin and mucosal bleeding. ITP is a kind of disease with increased platelet destruction and impaired platelet production caused by autoimmunity. Conventional treatment of adult ITP includes first-line glucocorticoid and immunoglobulin therapy, second-line TPO and TPO receptor agonist, splenectomy and other immunosuppressive treatments (such as rituximab, vincristine, azathioprine, etc.). ITP is one of the most common hemorrhagic diseases. At present, the treatment response of ITP is not good, and a considerable number of patients need drug maintenance treatment, which seriously affects the quality of life of patients and increases the economic burden of patients. Therefore, there is still a lack of effective treatment for adult ITP, especially for refractory ITP patients, which is one of the problems that have attracted more attention and need to be solved urgently.

BTK inhibitors can affect autoimmune diseases (AID) involving B cells and non-B cells through B cell receptor, Fc receptor and RANK receptor signals, such as systemic lupus erythematosus (SLE), multiple sclerosis (MS) and rheumatoid arthritis (RA) .Therefore, small molecule BTK inhibitors can treat autoimmune diseases by targeting B cells. At present, clinical studies on the treatment of immune thrombocytopenia with BTK inhibitor (BRN1008) have been carried out abroad. The preliminary results show that 50% of patients in the treatment ≥ 12 weeks and the initial dose is 400 mg BID group have reached the primary endpoint and maintained platelet response.

Zebutinib is a new selective Bruton tyrosine kinase (BTK) inhibitor developed by Baekje Shenzhou Company of China. In November 2019, it was approved by the US Food and Drug Administration to treat adult mantle cell lymphoma (MCL) patients who had received at least one treatment before. Compared with the first generation BTK inhibitors (ibutinib and acalabrutinib), zebutinib has stronger targeting and fewer adverse reactions.

Therefore, the investigators designed this clinical trial to provide new treatment options for clinical treatment of ITP.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yunfei Chen; Phone Number: +8618502220788; Email: chenyunfei@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Chinese Academy of Medical Science and Blood Disease Hospital
      • Contact: Yunfei Chen, MD; Phone Number: +86-22-23909009; Email: chenyunfei@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 and above, male or female；
• Conform to the diagnostic criteria of immune Thrombocytopenia (ITP)；
• Diagnosis of ITP>3 months；
• Primary ITP with a platelet count of <30 X 109/L prior to inclusion with failure to achieve response or relapse after corticosteroid therapy, and at least one second-line therapy including rituximab >12 weeks ago and/or TPO-RAs.
• Liver and kidney function, such as ALT, AST, BUN, SCR < 1.5 × upper limit of normal value, passing physical examination;
• ECOG physical state score ≤ 2 points；
• Cardiac function of the New York Society of Cardiac Function ≤ 2；
• Signed and dated written informed consent.

Exclusion Criteria:

• Uncontrollable primary diseases of important organs, such as malignant tumors, liver failure, heart failure, renal failure and other diseases;
• HIV positive;
• Accompanied by uncontrollable active infection, including hepatitis B, hepatitis C, cytomegalovirus, EB virus and syphilis positive;
• Accompanied by extensive and severe bleeding, such as hemoptysis, upper gastrointestinal hemorrhage, intracranial hemorrhage, etc.;
• At present, there are heart diseases, arrhythmias that need treatment or hypertension that researchers judge is poorly controlled;
• Patients with thrombotic diseases such as pulmonary embolism, thrombosis and atherosclerosis;
• Those who have received allogeneic stem cell transplantation or organ transplantation in the past;
• Patients with mental disorders who cannot normally obtain informed consent and conduct trials and follow-up;
• Patients whose toxic symptoms caused by pre-trial treatment have not disappeared;
• Other serious diseases that may limit the subject's participation in this test (such as diabetes; Severe cardiac insufficiency; Myocardial obstruction or unstable arrhythmia or unstable angina pectoris in recent 6 months; Gastric ulcer, etc.);
• Patients with septicemia or other irregular severe bleeding;
• Patients taking antiplatelet drugs at the same time;
• Pregnant women, suspected pregnancies (positive pregnancy test for human chorionic gonadotropin in urine at screening) and lactating patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention ( zanubrutinib); 30 enrolled patients are picked up to take zanubrutinib at the indicated dose.

Drug: Zanubrutinib; The initial dose is 80mg/day. If the treatment is ineffective after 4 weeks, and under the condition of good safety, the investigator will judge that the dosage should be added to 80mg twice/day，or a higher dose for oral maintenance. The maximum dose is 160mg twice a day. The duration of zanubrutinib is 24 weeks. In case of intolerable adverse reactions, such as severe infection, severe bleeding, hematopenia, arrhythmia, etc., investigator can reduce the dose of zanubrutinib, or withdraw from clinical trials as appropriate.; Other Names: The treatment of zanubrutinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with a platelet count ≥ 30 × 10^9/L and 50×10^9/L at week 12(Day 85)	Observe the changes of blood routine platelet count after 12 weeks of treatment, and calculate the proportion and times of subjects ≥ 30 × 10^9/L and 50 × 10^9/L.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistent platelet response with clinical significance at 24 weeks	Response defined as as the proportion of subjects with platelet count ≥ 50 × 109/L in at least 4 of the last 6 visits within 24 weeks without rescue treatment.	24 weeks
Number of participants with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale.	The WHO Bleeding Scale is a measure of bleeding severity with the following grades: grade 0 = no bleeding, grade 1= petechiae, grade 2= mild blood loss, grade 3 = gross blood loss, and grade 4 = debilitating blood loss.	24 weeks
The occurrence of adverse events during treatment (AE/SAE), treatment-related adverse events (TRAE) and serious adverse events (TRSAE)	The occurrence of adverse events during treatment (AE/SAE), treatment-related adverse events (TRAE) and serious adverse events (TRSAE)	24 weeks
Measurements of antibodies and various subsets of immunocompetent cells	Changes of anti-GPIIb/IIIa and Ib antibody and and various subsets of immunocompetent cells during study	24 weeks

Collaborators and Investigators

• Sponsor: Zhang Lei
• Investigators: Principal Investigator: Lei Zhang, MD, Chinese Academy of Medical Science and Blood Disease Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): February 15, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: January 19, 2022
• First Submitted That Met QC Criteria: January 19, 2022
• First Posted (Actual): January 28, 2022

Study Record Updates

• Last Update Posted (Actual): January 28, 2022
• Last Update Submitted That Met QC Criteria: January 19, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Zanubrutinib
• Other Study ID Numbers: IIT2021047-EC-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Researchers qualified can request the dataset, including de-identified individual subject data. Data may be requested from PI from 12 months 36 months after study completion.
• IPD Sharing Time Frame: 12 months to 36 months after study completion
• IPD Sharing Access Criteria: Upon request to PI.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes