Zanubrutinib in Patients With IgG4-Related Disease

Study Overview
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Brief Summary
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The aim of this clinical trial is to evaluate the safety and efficacy of zanubrutinib in treating patients with IgG4-related disease

Detailed Description
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This will be a single-site, open-label study in symptomatic patients with IgG4-related disease affecting the submandibular and/or lacrimal glands. All patients will receive zanubrutinib orally at a dose of 80mg BID for 24 weeks. The primary objective of this study is to demonstrate that zanubrutinib treatment reduces reduces the volume of the submandibular and/or lacrimal glands on PET/MRI at week 24 compared to baseline.

Official Title
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A Phase II, Single-Site, Open-Label Study of Zanubrutinib in Patients With IgG4-Related Disease

Conditions
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IgG4 Related Disease

Intervention / Treatment
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* Drug: Zanubrutinib 80 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women aged 18 to 85, inclusive, at the time of initial screening Have histopathologically confirmed IgG4-RD in the submandibular gland and/or the lacrimal gland confirmed by international consensus pathology criteria Presence of a lymphoplasmacytic infiltrate with 10 IgG4+ plasma cells per high-power field and/or an IgG4+/IgG+ plasma cell ratio of 40% All women must test negative for pregnancy and agree to use a reliable method of birth control No current treatment with immunosuppressive medications other than prednisone 40mg daily (or other glucocorticoid equivalent) with stable dosing for 28 days Exclusion Criteria: Unstable prescribed dose of glucocorticoids within 28 days prior to baseline Any treatment with a synthetic DMARD including but not limited to hydroxychloroquine, methotrexate, leflunomide, or sulfasalazine within 28 days prior to baseline Any treatment with a cytotoxic or immunosuppressive drug including but not limited to cyclophosphamide, mycophenolic acid, azathioprine, cyclosporine, sirolimus, or tacrolimus within 28 days prior to baseline Any treatment with a BTK inhibitor within 6 months before baseline Any treatment with a JAK inhibitor within 28 days prior to baseline Use of biologic agents including infliximab, abatacept, or tocilizumab within 56 days prior to baseline Use of a B cell depleting therapy (such as rituximab) within 12 months prior to baseline A history of, or current, inflammatory or autoimmune disease (that could affect the interpretation of safety or efficacy outcomes) other than IgG4-related disease Evidence of active tuberculosis, HIV, or hepatitis B or C infection History of cancer other than non-melanoma skin cancer, cervical dysplasia or carcinoma in situ (cured >1 year), prostate cancer (cured >5 years), or colon cancer (cured >5 years)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label study in symptomatic subjects with histopathologically confirmed IgG4-related disease affecting the submandibular and/or lacrimal glands. Ten subjects will be included in the study. All eligible subjects will receive zanubrutinib 80mg BID over a period of 24 weeks and will be followed up for an additional 8 weeks after the last dose.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zanubrutinib<br>Zanubrutinib orally at a dose of 80mg BID for 24 weeks | Drug: Zanubrutinib 80 MG<br>* Zanubrutinib 80 MG for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of the submandibular glands on PET-MRI | To demonstrate that zanubrutinib treatment reduces the volume of the submandibular glands on PET-MRI at Week 24 compared to Baseline. | Baseline to Week 24 | 
| Volume of the lacrimal glands on PET-MRI | To demonstrate that zanubrutinib treatment reduces the volume of the lacrimal glands on PET-MRI at Week 24 compared to Baseline. | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FDG avidity (SUVmax) of the submandibular glands on PET-MRI | Effect of zanubrutinib on change in FDG avidity (SUVmax) of the submandibular glands on PET-MRI at Week 24 compared to Baseline. | Baseline to Week 24 | 
| FDG avidity (SUVmax) of the lacrimal glands on PET-MRI | Effect of zanubrutinib on change in FDG avidity (SUVmax) of the lacrimal glands on PET-MRI at Week 24 compared to Baseline. | Baseline to Week 24 |