IgG4 Related DiseasePhase 2NCT04602598
Zanubrutinib in Patients With IgG4-Related Disease
A Phase 2 study testing Zanubrutinib 80 MG in people with IgG4 Related Disease, run by Matthew C. Baker at 1 site in United States.
Trial summary
The aim of this clinical trial is to evaluate the safety and efficacy of zanubrutinib in treating patients with IgG4-related disease Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- IgG4 Related Disease
- What is being tested?
- Zanubrutinib 80 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2022to 3 Apr 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II, Single-Site, Open-Label Study of Zanubrutinib in Patients With IgG4-Related Disease
The aim of this clinical trial is to evaluate the safety and efficacy of zanubrutinib in treating patients with IgG4-related disease
Read the 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.
- Conditions
- IgG4 Related Disease
- Being tested
- Zanubrutinib 80 MG
- Medical subject headings
- Immunoglobulin G4-Related Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zanubrutinib 80 MGDrug
Zanubrutinib 80 MG for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Zanubrutinib | Experimental | Zanubrutinib orally at a dose of 80mg BID for 24 weeks Receives: Drug: Zanubrutinib 80 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 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.
Measured: Baseline and Week 24
Secondary outcomes (34)
FDG Avidity (SUVmax) of the Submandibular Glands on PET
Effect of zanubrutinib on change in FDG avidity (SUVmax) of the submandibular glands on PET at Weeks 12 and 24 compared to Baseline.
Measured: Baseline, Week 12, and Week 24
FDG Avidity (SUVmax) of the Lacrimal Glands on PET
Effect of zanubrutinib on change in FDG avidity (SUVmax) of the lacrimal glands on PET at Week 24 compared to Baseline.
Measured: Baseline, Week 12, and Week 24
Change in Total Metabolic Lesion Volume (tMLV) of Lacrimal Glands, Submandibular Glands, Parotid Glands, and Lymph Notes on PET
Measured: Baseline, Week 12, and Week 24
Change in Total Lesion Glycolysis (TLG) of Submandibular and/or Lacrimal Glands on PET
Measured: Baseline, Week 12, and Week 24
Change in Submandibular Glands on MRI
Change in parenchymal architecture scored 0 to 4 and sialography scored 0 to 4 where 0 is normal, healthy gland and 4 is worse outcome.
Measured: Baseline, Week 12, and Week 24
Change in Parotid Glands on MRI
Change in parenchymal architecture scored 0 to 4 and sialography scored 0 to 4, where 0 is normal, healthy gland and 4 is worse outcome.
Measured: Baseline, Week 12, and Week 24
Change in Lacrimal Glands on MRI
Change in parenchymal architecture scored 0 to 4, where 0 is normal, healthy gland and 4 is worse outcome.
Measured: Baseline, Week 12, and Week 24
Change in the Volume of the Parotid Glands on PET/MRI
Measured: Baseline, Week 12, and Week 24
Change in the Volume of the Submandibular Glands on PET/MRI
Measured: Baseline and Week 12
Change in the Volume of the Lacrimal Glands on PET/MRI
Measured: Baseline, and Week 12
Change in Serum IgG4 Level
Measured: Baseline, Week 12, and Week 24
Change in Plasmablast Count
Change in percentage of CD19+ B cells in blood
Measured: Baseline, Week 12, and Week 24
Change in Absolute Regulatory B Cell Count
Percentage of regulatory B cells in the blood, assessed using flow cytometry.
Measured: Baseline, Week 12, and Week 24
Change in the IgG4-RD Responder Index
The IgG4-RD Responder Index detects change in disease activity and identifies improvements/worsening in the same or different organ systems. It encompasses more than 25 organs/sites and records the following for each organ/site: (i) activity trend (through a 0-3 [normal/resolved - worsening] organ/site score); (ii) presence of symptoms due to active disease; (iii) need for urgent care; (iv) presence of damage; and (v) presence of symptoms due to damage. The final activity score at each visit is obtained by summing all organ/site scores (i) and by doubling items needing urgent care (iii). The IgG4-RD Responder Index Total Activity Score ranges from 0 to a maximum of 162. Higher scores represent greater (i.e. worse) disease activity. A score of 0 represents no disease activity other than residual fibrosis.
Measured: Baseline, Week 12, and Week 24
Proportion of Patients With no Disease Flares
Number and percentage of patients who did not have an IgG4-RD flare
Measured: Week 12 to Week 24
Change in Total Salivary Grey Scale Ultrasound Score (TUS)
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 (overall score range: 0 to 12, with a higher score indicating worse disease)
Measured: Baseline, Week 12, and Week 24
Change in Highest Score Among the Salivary Glands for the Grey Scale Ultrasound Score (HSUS)
Each parotid and submandibular gland (n=4) scored from 0 to 3 with a higher score indicating worse disease, highest score will be assessed for change (overall score range: 0 to 12, with a higher score indicating worse disease)
Measured: Baseline, Week 12, and Week 24
Change in Glandular Inflammation Total Ultrasound Score (iTUS)
Each parotid and submandibular gland (n=4) scored from 0 to 3 with a higher score indicating worse disease, total summed scores across all four glands will be assessed for change (overall score range: 0 to 12, with a higher score indicating worse disease)
Measured: Baseline, Week 12, and Week 24
Change in Highest Score Among the Salivary Glands for the Glandular Inflammation Ultrasound Score (iHSUS)
Each parotid and submandibular gland (n=4) scored from 0 to 3 with a higher score indicating worse disease, highest score will be assessed for change (overall score range: 0 to 12, with a higher score indicating worse disease)
Measured: Baseline, Week 12, and Week 24
Change in Physician Global Assessment of Disease
Symptoms rated on a 100 mm visual analog scale (VAS). Score range: 0 to 100, higher scores correspond to worse disease state.
Measured: Baseline, Week 12, and Week 24
Change in Patient Global Assessment of Disease
Symptoms rated on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state.
Measured: Baseline, Week 12, and Week 24
Change in VAS for Ocular Symptoms - Dryness
Symptoms rated on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state.
Measured: Baseline to Week 24
Change in VAS for Dryness Symptoms
Symptoms rated on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to more dryness. Participants were asked to assess their dryness, taking into account all areas, including ocular and salivary symptoms.
Measured: Baseline, Week 12, Week 24
Change in FACIT-F Fatigue Score
Total score range: 0-52, lower scores correspond with more fatigue. FACIT = Functional Assessment of Chronic Illness Therapy.
Measured: Baseline, Week 12, and Week 24
Change in RAND Short Form-36
The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health.
Measured: Baseline, Week 12, and Week 24
Change in C3 Lab
Complement component 3 (C3) level in blood
Measured: Baseline, Week 12, and Week 24
Change in C4 Lab
Complement component 4 (C4) level in blood
Measured: Baseline, Week 12, and Week 24
Change in Total IgG Lab
Measured: Baseline, Week 12, and Week 24
Change in IgE Lab
Measured: Baseline, Week 12, and Week 24
Change in IgG1 Lab
Measured: Baseline, Week 12, and Week 24
Change in ESR Lab
Change in erythrocyte sedimentation rate (ESR)
Measured: Baseline, Week 12, and Week 24
Change in CRP Lab
Change in serum C-reactive protein (CRP) level
Measured: Baseline, Week 12, and Week 24
Incidence of Safety Parameters Including Adverse Events
Number of participants with treatment-emergent adverse events (TEAEs).
Measured: Baseline to Week 32
Incidence of Safety Parameters Including Abnormal Laboratory Results
Number of participants with any grade 3 or 4 treatment-emergent laboratory abnormality
Measured: Baseline to Week 32
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2020
- Study start1 Aug 2022
- Primary completion11 Feb 2025
- Study completion3 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for IgG4 Related DiseaseStudies of the same condition, open and under way.
- 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
- 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)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Matthew C. Baker
- Sponsor type
- University, hospital or other
- Collaborators
- Stanford University
- Responsible party
- Sponsor-investigator, Matthew C. Baker, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04602598
- Sponsor's protocol ID
- 58497
- Status last verified
- Mar 2026
- First submitted
- 20 Oct 2020
- Last updated
- 1 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Single-Site, Open-Label Study of Zanubrutinib in Patients With IgG4-Related Disease
- ClinicalTrials.gov ID
- NCT04602598
- Acronym / sponsor ID
- 58497
- Conditions
- IgG4 Related Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Matthew C. BakerUniversity, hospital or other
- Collaborators
- Stanford University
- Study start
- 1 Aug 2022 (actual)
- Primary completion
- 11 Feb 2025 (actual)
- Study completion
- 3 Apr 2025 (actual)
- First posted
- 26 Oct 2020 (actual)
- Results
- Posted 1 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Zanubrutinib | Experimental | Drug: Zanubrutinib 80 MGZanubrutinib orally at a dose of 80mg BID for 24 weeks |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
- 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
Key exclusion criteria (10 listed)
- 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
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 |
|---|---|---|
| Zanubrutinib 80 MGZanubrutinib 80 MG for 24 weeks | Drug | Zanubrutinib |
Primary outcome
Volume of the Submandibular Glands on PET-MRI
Time frame: Baseline and Week 24
To demonstrate that zanubrutinib treatment reduces the volume of the submandibular glands on PET-MRI at week 24 compared to Baseline.
Volume of the Lacrimal Glands on PET-MRI
Time frame: Baseline and Week 24
To demonstrate that zanubrutinib treatment reduces the volume of the lacrimal glands on PET-MRI at Week 24 compared to Baseline.
34 secondary outcomes
FDG Avidity (SUVmax) of the Submandibular Glands on PET
Time frame: Baseline, Week 12, and Week 24
FDG Avidity (SUVmax) of the Lacrimal Glands on PET
Time frame: Baseline, Week 12, and Week 24
Change in Total Metabolic Lesion Volume (tMLV) of Lacrimal Glands, Submandibular Glands, Parotid Glands, and Lymph Notes on PET
Time frame: Baseline, Week 12, and Week 24
Change in Total Lesion Glycolysis (TLG) of Submandibular and/or Lacrimal Glands on PET
Time frame: Baseline, Week 12, and Week 24
Change in Submandibular Glands on MRI
Time frame: Baseline, Week 12, and Week 24
Change in Parotid Glands on MRI
Time frame: Baseline, Week 12, and Week 24
Change in Lacrimal Glands on MRI
Time frame: Baseline, Week 12, and Week 24
Change in the Volume of the Parotid Glands on PET/MRI
Time frame: Baseline, Week 12, and Week 24
Change in the Volume of the Submandibular Glands on PET/MRI
Time frame: Baseline and Week 12
Change in the Volume of the Lacrimal Glands on PET/MRI
Time frame: Baseline, and Week 12
Change in Serum IgG4 Level
Time frame: Baseline, Week 12, and Week 24
Change in Plasmablast Count
Time frame: Baseline, Week 12, and Week 24
Change in Absolute Regulatory B Cell Count
Time frame: Baseline, Week 12, and Week 24
Change in the IgG4-RD Responder Index
Time frame: Baseline, Week 12, and Week 24
Proportion of Patients With no Disease Flares
Time frame: Week 12 to Week 24
Change in Total Salivary Grey Scale Ultrasound Score (TUS)
Time frame: Baseline, Week 12, and Week 24
Change in Highest Score Among the Salivary Glands for the Grey Scale Ultrasound Score (HSUS)
Time frame: Baseline, Week 12, and Week 24
Change in Glandular Inflammation Total Ultrasound Score (iTUS)
Time frame: Baseline, Week 12, and Week 24
Change in Highest Score Among the Salivary Glands for the Glandular Inflammation Ultrasound Score (iHSUS)
Time frame: Baseline, Week 12, and Week 24
Change in Physician Global Assessment of Disease
Time frame: Baseline, Week 12, and Week 24
Change in Patient Global Assessment of Disease
Time frame: Baseline, Week 12, and Week 24
Change in VAS for Ocular Symptoms - Dryness
Time frame: Baseline to Week 24
Change in VAS for Dryness Symptoms
Time frame: Baseline, Week 12, Week 24
Change in FACIT-F Fatigue Score
Time frame: Baseline, Week 12, and Week 24
Change in RAND Short Form-36
Time frame: Baseline, Week 12, and Week 24
Change in C3 Lab
Time frame: Baseline, Week 12, and Week 24
Change in C4 Lab
Time frame: Baseline, Week 12, and Week 24
Change in Total IgG Lab
Time frame: Baseline, Week 12, and Week 24
Change in IgE Lab
Time frame: Baseline, Week 12, and Week 24
Change in IgG1 Lab
Time frame: Baseline, Week 12, and Week 24
Change in ESR Lab
Time frame: Baseline, Week 12, and Week 24
Change in CRP Lab
Time frame: Baseline, Week 12, and Week 24
Incidence of Safety Parameters Including Adverse Events
Time frame: Baseline to Week 32
Incidence of Safety Parameters Including Abnormal Laboratory Results
Time frame: Baseline to Week 32
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site 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 80 MG in people with IgG4 Related Disease, run by Matthew C. Baker at 1 site in United States.
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 5 inclusion and 10 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: finished, as of the sponsor's last update on 1 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Yes. Results are posted in the registry (first posted 1 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Volume of the Submandibular Glands on PET-MRI (time frame: Baseline and Week 24). The study lists 2 primary outcomes in all. 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 1 Apr 2026.