Zanubrutinib in Patients With IgG4-Related Disease
- Registration Number
- NCT04602598
- Lead Sponsor
- Matthew C. Baker
- Brief Summary
The aim of this clinical trial is to evaluate the safety and efficacy of zanubrutinib in treating patients with IgG4-related disease
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 10
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Men or women aged 18 to 85, inclusive, at the time of initial screening
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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%
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All women must test negative for pregnancy and agree to use a reliable method of birth control
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No current treatment with immunosuppressive medications other than prednisone 40mg daily (or other glucocorticoid equivalent) with stable dosing for 28 days
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Zanubrutinib Zanubrutinib 80 MG Zanubrutinib orally at a dose of 80mg BID for 24 weeks
- Primary Outcome Measures
Name Time Method Volume of the lacrimal glands on PET-MRI Baseline to Week 24 To demonstrate that zanubrutinib treatment reduces the volume of the lacrimal glands on PET-MRI at Week 24 compared to Baseline.
Volume of the submandibular glands on PET-MRI Baseline to Week 24 To demonstrate that zanubrutinib treatment reduces the volume of the submandibular glands on PET-MRI at Week 24 compared to Baseline.
- Secondary Outcome Measures
Name Time Method FDG avidity (SUVmax) of the submandibular glands on PET Baseline to Week 24 Effect of zanubrutinib on change in FDG avidity (SUVmax) of the submandibular glands on PET at Week 24 compared to Baseline.
FDG avidity (SUVmax) of the lacrimal glands on PET Baseline to Week 24 Effect of zanubrutinib on change in FDG avidity (SUVmax) of the lacrimal glands on PET at Week 24 compared to Baseline.
Change in metabolic lesion volume (MLV) of submandibular and/or lacrimal glands on PET Baseline to Week 12 Change in total lesion glycolysis (TLG) of submandibular and/or lacrimal glands on PET Baseline to Week 12 Change in submandibular glands on MRI Baseline to Week 12 Change in parenchymal architecture scored 0 to 4 and sialography scored 0 to 4
Change in parotid glands on MRI Baseline to Week 12 Change in parenchymal architecture scored 0 to 4 and sialography scored 0 to 4
Change in lacrimal glands on MRI Baseline to Week 12 Change in parenchmyal architecture scored 0 to 4 and sialography scored 0 to 4
Change in the volume of the parotid glands on PET/MRI Baseline to Week 12 Change in the volume of the submandibular glands on PET/MRI Baseline to Week 12 Change in the volume of the lacrimal glands on PET/MRI Baseline to Week 12 FDG avidity (SUVmax) of the submandibular and/or lacrimal glands on PET Baseline to Week 12 Effect of zanubrutinib on change in FDG avidity (SUVmax) of the submandibular and/or lacrimal glands on PET at Week 12 compared to Baseline.
Change in serum IgG4 level Baseline to Week 12 Change in plasmablast count Baseline to Week 12 Change in absolute regulatory B cell count Baseline to Week 12 Change in the IgG4-RD Responder Index Baseline to Week 12 Proportion of patients with no disease flares Week 12 to Week 24 Change in total salivary grey scale ultrasound score (TUS) Baseline to Week 12 Each parotid and submandibular gland scored from 0 to 3 with a higher score indicating worse disease, total summed scores across all four glands will be assessed for change
Change in highest score among the salivary glands for the grey scale ultrasound score (HSUS) Baseline to Week 12 Each parotid and submandibular gland scored from 0 to 3 with a higher score indicating worse disease, highest score will be assessed for change
Change in glandular inflammation total ultrasound score (iTUS) Baseline to Week 12 Each parotid and submandibular gland scored from 0 to 3 with a higher score indicating worse disease, total summed scores across all four glands will be assessed for change
Change in highest score among the salivary glands for the glandular inflammation ultrasound score (iHSUS) Baseline to Week 12 Each parotid and submandibular gland scored from 0 to 3 with a higher score indicating worse disease, highest score will be assessed for change
Change in physician global assessment of disease Baseline to Week 12 Symptoms rated on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state.
Change in patient global assessment of disease Baseline to Week 12 Symptoms rated on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state.
Change in VAS for ocular symptoms Baseline to Week 12 Symptoms rated on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state.
Change in VAS for salivary symptoms Baseline to Week 12 Symptoms rated on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state.
Change in FACIT-F fatigue score Baseline to Week 12 Total score range: 0-52, lower scores correspond with more fatigue.
Change in RAND Short Form-36 Baseline to Week 12 Change in C3 lab Baseline to Week 12 Change in C4 lab Baseline to Week 12 Change in total IgG lab Baseline to Week 12 Change in IgE lab Baseline to Week 12 Change in IgG1 lab Baseline to Week 12 Change in ESR lab Baseline to Week 12 Change in CRP lab Baseline to Week 12 Incidence of safety parameters including adverse events Baseline to Week 32 Incidence of safety parameters including abnormal laboratory results Baseline to Week 32
Trial Locations
- Locations (1)
Stanford University
🇺🇸Palo Alto, California, United States