Clinical trial NCT04602598: Zanubrutinib in Patients With IgG4-Related Disease
Official title: A Phase II, Single-Site, Open-Label Study of Zanubrutinib in Patients With IgG4-Related Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: IgG4 Related Disease
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Stanford University
First posted: 2020-10-26
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Volume of the submandibular glands on PET-MRI
timeFrame: Baseline to Week 24
measure: Volume of the lacrimal glands on PET-MRI
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: FDG avidity (SUVmax) of the submandibular glands on PET
timeFrame: Baseline to Week 24
measure: FDG avidity (SUVmax) of the lacrimal glands on PET
timeFrame: Baseline to Week 24
measure: Change in metabolic lesion volume (MLV) of submandibular and/or lacrimal glands on PET
timeFrame: Baseline to Week 24
measure: Change in total lesion glycolysis (TLG) of submandibular and/or lacrimal glands on PET
timeFrame: Baseline to Week 24
measure: Change in submandibular glands on MRI
timeFrame: Baseline to Week 24
measure: Change in parotid glands on MRI
timeFrame: Baseline to Week 24
measure: Change in lacrimal glands on MRI
timeFrame: Baseline to Week 24
measure: Change in the volume of the parotid glands on PET/MRI
timeFrame: Baseline to Week 24
measure: Change in the volume of the submandibular glands on PET/MRI
timeFrame: Baseline to Week 12
measure: Change in the volume of the lacrimal glands on PET/MRI
timeFrame: Baseline to Week 12
measure: Change in the volume of the parotid glands on PET/MRI
timeFrame: Baseline to Week 12
measure: FDG avidity (SUVmax) of the submandibular and/or lacrimal glands on PET
timeFrame: Baseline to Week 12
measure: Change in metabolic lesion volume (MLV) of submandibular and/or lacrimal glands on PET
timeFrame: Baseline to Week 12
measure: Change in total lesion glycolysis (TLG) of submandibular and/or lacrimal glands on PET
timeFrame: Baseline to Week 12
measure: Change in submandibular glands on MRI
timeFrame: Baseline to Week 12
measure: Change in parotid glands on MRI
timeFrame: Baseline to Week 12
measure: Change in lacrimal glands on MRI
timeFrame: Baseline to Week 12
measure: Change in serum IgG4 level
timeFrame: Baseline to Week 24
measure: Change in serum IgG4 level
timeFrame: Baseline to Week 12
measure: Change in plasmablast count
timeFrame: Baseline to Week 24
measure: Change in plasmablast count
timeFrame: Baseline to Week 12
measure: Change in absolute regulatory B cell count
timeFrame: Baseline to Week 24
measure: Change in absolute regulatory B cell count
timeFrame: Baseline to Week 12
measure: Change in the IgG4-RD Responder Index
timeFrame: Baseline to Week 24
measure: Change in the IgG4-RD Responder Index
timeFrame: Baseline to Week 12
measure: Proportion of patients with no disease flares
timeFrame: Week 12 to Week 24
measure: Change in total salivary grey scale ultrasound score (TUS)
timeFrame: Baseline to Week 24
measure: Change in total salivary grey scale ultrasound score (TUS)
timeFrame: Baseline to Week 12
measure: Change in highest score among the salivary glands for the grey scale ultrasound score (HSUS)
timeFrame: Baseline to Week 24
measure: Change in highest score among the salivary glands for the grey scale ultrasound score (HSUS)
timeFrame: Baseline to Week 12
measure: Change in glandular inflammation total ultrasound score (iTUS)
timeFrame: Baseline to Week 24
measure: Change in glandular inflammation total ultrasound score (iTUS)
timeFrame: Baseline to Week 12
measure: Change in highest score among the salivary glands for the glandular inflammation ultrasound score (iHSUS)
timeFrame: Baseline to Week 24
measure: Change in highest score among the salivary glands for the glandular inflammation ultrasound score (iHSUS)
timeFrame: Baseline to Week 12
measure: Change in physician global assessment of disease
timeFrame: Baseline to Week 24
measure: Change in physician global assessment of disease
timeFrame: Baseline to Week 12
measure: Change in patient global assessment of disease
timeFrame: Baseline to Week 24
measure: Change in patient global assessment of disease
timeFrame: Baseline to Week 12
measure: Change in VAS for ocular symptoms
timeFrame: Baseline to Week 24
measure: Change in VAS for ocular symptoms
timeFrame: Baseline to Week 12
measure: Change in VAS for salivary symptoms
timeFrame: Baseline to Week 24
measure: Change in VAS for salivary symptoms
timeFrame: Baseline to Week 12
measure: Change in FACIT-F fatigue score
timeFrame: Baseline to Week 24
measure: Change in FACIT-F fatigue score
timeFrame: Baseline to Week 12
measure: Change in RAND Short Form-36
timeFrame: Baseline to Week 24
measure: Change in RAND Short Form-36
timeFrame: Baseline to Week 12
measure: Change in C3 lab
timeFrame: Baseline to Week 24
measure: Change in C3 lab
timeFrame: Baseline to Week 12
measure: Change in C4 lab
timeFrame: Baseline to Week 24
measure: Change in C4 lab
timeFrame: Baseline to Week 12
measure: Change in total IgG lab
timeFrame: Baseline to Week 24
measure: Change in total IgG lab
timeFrame: Baseline to Week 12
measure: Change in IgE lab
timeFrame: Baseline to Week 24
measure: Change in IgE lab
timeFrame: Baseline to Week 12
measure: Change in IgG1 lab
timeFrame: Baseline to Week 24
measure: Change in IgG1 lab
timeFrame: Baseline to Week 12
measure: Change in ESR lab
timeFrame: Baseline to Week 24
measure: Change in ESR lab
timeFrame: Baseline to Week 12
measure: Change in CRP lab
timeFrame: Baseline to Week 24
measure: Change in CRP lab
timeFrame: Baseline to Week 12
measure: Incidence of safety parameters including adverse events
timeFrame: Baseline to Week 32
measure: Incidence of safety parameters including abnormal laboratory results
timeFrame: Baseline to Week 32
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
Study officials:
References: