Antiphospholipid SyndromePhase 2NCT05199909
Safety and Efficacy of Zanubrutinib in the Treatment of Antiphospholipid Syndrome With Secondary Thrombocytopenia
A Phase 2 study testing zanubrutinib in people with Antiphospholipid Syndrome and Thrombocytopenia, run by Institute of Hematology & Blood Diseases Hospital, China at 2 sites in China.
Trial summary
To evaluate the safety and efficacy of zanubrutinib in the treatment of antiphospholipid syndrome with secondary thrombocytopenia in 10 patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Antiphospholipid Syndrome, Thrombocytopenia, Treatment
- What is being tested?
- zanubrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesChina
- Study dates
- 25 Jan 2022to 30 Jun 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 and above, male or female；
- Diagnosis of antiphospholipid syndrome；
- Failure to receive glucocorticoid treatment in the past (the curative effect cannot be maintained, or recurs, or cannot be tolerated); Can not choose other second-line treatment, such as rituximab, cyclosporine, cyclophosphamide, etc.; Or rituximab, cyclosporine and other treatments are ineffective, relapsed or intolerable;
- Plt < 30×10^9/L；
- 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.
Who cannot join
- 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 new pulmonary embolism and unstable period of various arteriovenous thrombosis;
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- 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;
- Pregnant women, suspected pregnancies (positive pregnancy test for human chorionic gonadotropin in urine at screening) and lactating patients.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Chinese Academy of Medical Science and Blood Disease Hospital
Tianjin, Tianjin Municipality, 300020
Yunfei Chen, MD, +86-22-23909009, chenyunfei@ihcams.ac.cn
- Recruiting
Institute of Hematology & Blood Diseases Hospital
Tianjin, Tianjin Municipality, 300020
Lei Zhang, MD, +862223909240, zhanglei1@ihcams.ac.cn
About this study
Official title: Prospective, Single Arm and Open Clinical Observation of Zanubrutinib in the Treatment of Antiphospholipid Syndrome With Secondary Thrombocytopenia
To evaluate the safety and efficacy of zanubrutinib in the treatment of antiphospholipid syndrome with secondary thrombocytopenia in 10 patients.
Read the detailed description
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.
- Conditions
- Antiphospholipid Syndrome, Thrombocytopenia, Treatment
- Being tested
- zanubrutinib
- Medical subject headings
- Antiphospholipid Syndrome, Thrombocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zanubrutinibDrug
Also called The treatment of 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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention ( zanubrutinib) | Experimental | 10 enrolled patients are picked up to take zanubrutinib at the indicated dose. Receives: Drug: zanubrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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)
Measured: 24 weeks
Evaluate the occurrence of thrombosis during treatment
Evaluate the occurrence of thrombosis during treatment
Measured: 24 weeks
Antiphospholipid antibody titre
To monitor antiphospholipid antibody titre during treatment in all participants.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2022
- Study start25 Jan 2022
- Primary completion31 Dec 2023
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Antiphospholipid SyndromeStudies of the same condition, open and under way.
- More trials run by Institute of Hematology & Blood Diseases Hospital, ChinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lei Zhang, MD, Principal investigator, Chinese Academy of Medical Science and Blood Disease Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05199909
- Sponsor's protocol ID
- IIT2021048
- Status last verified
- Jan 2025
- First submitted
- 30 Dec 2021
- Last updated
- 24 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Single Arm and Open Clinical Observation of Zanubrutinib in the Treatment of Antiphospholipid Syndrome With Secondary Thrombocytopenia
- ClinicalTrials.gov ID
- NCT05199909
- Acronym / sponsor ID
- IIT2021048
- Conditions
- Antiphospholipid Syndrome, Thrombocytopenia, Treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
- Study start
- 25 Jan 2022 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 20 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the safety and efficacy of zanubrutinib in the treatment of antiphospholipid syndrome with secondary thrombocytopenia in 10 patients.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention ( zanubrutinib) | Experimental | Drug: zanubrutinib10 enrolled patients are picked up to take zanubrutinib at the indicated dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 and above, male or female；
- Diagnosis of antiphospholipid syndrome；
- Failure to receive glucocorticoid treatment in the past (the curative effect cannot be maintained, or recurs, or cannot be tolerated); Can not choose other second-line treatment, such as rituximab, cyclosporine, cyclophosphamide, etc.; Or rituximab, cyclosporine and other treatments are ineffective, relapsed or intolerable;
- Plt < 30×10^9/L；
- Liver and kidney function, such as ALT, AST, BUN, SCR < 1.5 × upper limit of normal value, passing physical examination;
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| zanubrutinibAlso: The treatment of zanubrutinibThe 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. | Drug | Intervention ( zanubrutinib) |
Primary outcome
Proportion of subjects with a platelet count ≥ 30 × 10^9/L and 50×10^9/L at week 12(Day 85)
Time frame: 12 weeks
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.
5 secondary outcomes
Persistent platelet response with clinical significance at 24 weeks
Time frame: 24 weeks
Number of participants with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale.
Time frame: 24 weeks
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
Time frame: 24 weeks
Antiphospholipid antibody titre
Time frame: 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lei Zhang, MD principal investigator
Chinese Academy of Medical Science and Blood Disease Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing zanubrutinib in people with Antiphospholipid Syndrome and Thrombocytopenia, run by Institute of Hematology & Blood Diseases Hospital, China at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yunfei Chen, MD (+8618502220788, chenyunfei@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of subjects with a platelet count ≥ 30 × 10^9/L and 50×10^9/L at week 12(Day 85) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2025.