A Phase 2 interventional study of zanubrutinib in Antiphospholipid Syndrome, Thrombocytopenia and Treatment, sponsored by Institute of Hematology & Blood Diseases Hospital, China. Recruiting at 2 sites in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-02-24.
Sponsored by Institute of Hematology & Blood Diseases Hospital, China · Phase 2, Interventional, and Treatment
To evaluate the safety and efficacy of zanubrutinib in the treatment of antiphospholipid syndrome with secondary thrombocytopenia in 10 patients.
Antiphospholipid syndrome (APS) is a disease spectrum characterized by thrombosis and/or pathological pregnancy, and characterized by persistent antiphospholipid antibodies (APL) positive in laboratory examination. The incidence of thrombocytopenia in APS patients is 29.6%. Thrombocytopenia is usually mild to moderate without clinical manifestations, and the risk of bleeding is low. The platelet count of most patients is > 50 × 10\^9/L. If APS has severe thrombocytopenia and severe bleeding, it is very difficult to treat it. According to previous literature reports, Some patients were treated with hormones, rituximab and immunosuppressants. Platelets can be obviously increased, but they are easy to relapse and difficult to maintain. aPL is not obviously decreased and difficult to be completely eliminated. Thrombosis still occurs in some patients with obviously decreased platelets. Thrombopoietin receptor agonists increase the risk of thrombosis, which is a difficult point in hematology treatment at present.
Bruton tyrosine kinase (BTK), a member of the Tec family of non-receptor tyrosine kinases, is expressed in all hematopoietic cells except T cells and terminal differentiated plasma cells. BTK is a key kinase in BCR signaling pathway, which regulates B cell proliferation, survival, differentiation and cytokine expression. 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).
Besides its activity in B cells, BTK is also expressed in platelets and mediates the signal of cell surface receptor glycoprotein VI (GPVI). It is believed that BTK/Tec pathway may affect GP VI specific platelet signal deficiency and interfere with collagen adhesion and vWF-mediated platelet activation. BTK plays an important role in vWF-mediated signal transduction and GPIb-dependent thrombosis in vivo. Moreover, recent studies have found that BTK inhibitors can block the activation of platelets stimulated by FcγRIIA through antibody-mediated crosslinking (inducing platelet aggregation and secretion) or anti-CD9 antibody (only inducing platelet aggregation). Therefore, BTK inhibitors have certain antithrombotic effects at the same time. At present, there is no related report on BTK inhibitor in the treatment of APS abroad. BTK inhibitors can regulate B cell proliferation, survival, differentiation and cytokine expression, reduce antibody formation, and inhibit platelet adhesion and platelet activation, so they may have a good therapeutic effect on antiphospholipid syndrome.
Therefore, the investigators designed this clinical trial to provide a new treatment option for the clinical treatment of antiphospholipid syndrome with secondary thrombocytopenia.
125 studies on the registry are indexed under Antiphospholipid Syndrome; 55 are open to participants now.
This study's planned enrollment of 10 is below the median of 40 across 67 interventional studies indexed under Antiphospholipid Syndrome.
Browse Antiphospholipid Syndrome studies →Institute of Hematology & Blood Diseases Hospital, China is the lead sponsor of 402 studies on the registry; 296 are open to participants now.
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Exclusion Criteria:
10 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 researcher 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.
Also known as: The treatment of zanubrutinib
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.
Time frame: 12 weeks
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.
Time frame: 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.
Time frame: 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)
Time frame: 24 weeks
Evaluate the occurrence of thrombosis during treatment
Evaluate the occurrence of thrombosis during treatment
Time frame: 24 weeks
Antiphospholipid antibody titre
To monitor antiphospholipid antibody titre during treatment in all participants.
Time frame: 24 weeks
Plan to share: Yes — 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.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: 12 months to 36 months after study completion.
Access criteria: Upon request to PI.
No publications or documents are linked to this record.
Ran from Jan 2022 to primary completion in Dec 2023, 23 months.
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Studies of the drug tested here: Zanubrutinib
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