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Completed

NCT Number: NCT04602598

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

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Key information

Conditions

IgG4 Related Disease Autoimmune Diseases Immune System Diseases Immunoglobulin G4-Related Disease

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Stanford University

Palo Alto, California, 94304, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Zanubrutinib 80 MG

Drug

Zanubrutinib 80 MG for 24 weeks

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. FDG Avidity (SUVmax) of the Submandibular Glands on PET

    Time frame: Baseline, Week 12, and Week 24

    Effect of zanubrutinib on change in FDG avidity (SUVmax) of the submandibular glands on PET at Weeks 12 and 24 compared to Baseline.

  2. FDG Avidity (SUVmax) of the Lacrimal Glands on PET

    Time frame: Baseline, Week 12, and Week 24

    Effect of zanubrutinib on change in FDG avidity (SUVmax) of the lacrimal glands on PET at Week 24 compared to Baseline.

  3. 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

  4. Change in Total Lesion Glycolysis (TLG) of Submandibular and/or Lacrimal Glands on PET

    Time frame: Baseline, Week 12, and Week 24

  5. Change in Submandibular Glands on MRI

    Time frame: Baseline, Week 12, and Week 24

    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.

  6. Change in Parotid Glands on MRI

    Time frame: Baseline, Week 12, and Week 24

    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.

  7. Change in Lacrimal Glands on MRI

    Time frame: Baseline, Week 12, and Week 24

    Change in parenchymal architecture scored 0 to 4, where 0 is normal, healthy gland and 4 is worse outcome.

  8. Change in the Volume of the Parotid Glands on PET/MRI

    Time frame: Baseline, Week 12, and Week 24

  9. Change in the Volume of the Submandibular Glands on PET/MRI

    Time frame: Baseline and Week 12

  10. Change in the Volume of the Lacrimal Glands on PET/MRI

    Time frame: Baseline, and Week 12

  11. Change in Serum IgG4 Level

    Time frame: Baseline, Week 12, and Week 24

  12. Change in Plasmablast Count

    Time frame: Baseline, Week 12, and Week 24

    Change in percentage of CD19+ B cells in blood

  13. Change in Absolute Regulatory B Cell Count

    Time frame: Baseline, Week 12, and Week 24

    Percentage of regulatory B cells in the blood, assessed using flow cytometry.

  14. Change in the IgG4-RD Responder Index

    Time frame: Baseline, Week 12, and Week 24

    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.

  15. Proportion of Patients With no Disease Flares

    Time frame: Week 12 to Week 24

    Number and percentage of patients who did not have an IgG4-RD flare

  16. Change in Total Salivary Grey Scale Ultrasound Score (TUS)

    Time frame: Baseline, Week 12, and Week 24

    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)

  17. Change in Highest Score Among the Salivary Glands for the Grey Scale Ultrasound Score (HSUS)

    Time frame: Baseline, Week 12, and Week 24

    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)

  18. Change in Glandular Inflammation Total Ultrasound Score (iTUS)

    Time frame: Baseline, Week 12, and Week 24

    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)

  19. Change in Highest Score Among the Salivary Glands for the Glandular Inflammation Ultrasound Score (iHSUS)

    Time frame: Baseline, Week 12, and Week 24

    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)

  20. Change in Physician Global Assessment of Disease

    Time frame: Baseline, Week 12, and Week 24

    Symptoms rated on a 100 mm visual analog scale (VAS). Score range: 0 to 100, higher scores correspond to worse disease state.

  21. Change in Patient Global Assessment of Disease

    Time frame: Baseline, Week 12, and Week 24

    Symptoms rated on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state.

  22. Change in VAS for Ocular Symptoms - Dryness

    Time frame: Baseline to Week 24

    Symptoms rated on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state.

  23. Change in VAS for Dryness Symptoms

    Time frame: Baseline, Week 12, Week 24

    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.

  24. Change in FACIT-F Fatigue Score

    Time frame: Baseline, Week 12, and Week 24

    Total score range: 0-52, lower scores correspond with more fatigue. FACIT = Functional Assessment of Chronic Illness Therapy.

  25. Change in RAND Short Form-36

    Time frame: Baseline, Week 12, and Week 24

    The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health.

  26. Change in C3 Lab

    Time frame: Baseline, Week 12, and Week 24

    Complement component 3 (C3) level in blood

  27. Change in C4 Lab

    Time frame: Baseline, Week 12, and Week 24

    Complement component 4 (C4) level in blood

  28. Change in Total IgG Lab

    Time frame: Baseline, Week 12, and Week 24

  29. Change in IgE Lab

    Time frame: Baseline, Week 12, and Week 24

  30. Change in IgG1 Lab

    Time frame: Baseline, Week 12, and Week 24

  31. Change in ESR Lab

    Time frame: Baseline, Week 12, and Week 24

    Change in erythrocyte sedimentation rate (ESR)

  32. Change in CRP Lab

    Time frame: Baseline, Week 12, and Week 24

    Change in serum C-reactive protein (CRP) level

  33. Incidence of Safety Parameters Including Adverse Events

    Time frame: Baseline to Week 32

    Number of participants with treatment-emergent adverse events (TEAEs).

  34. Incidence of Safety Parameters Including Abnormal Laboratory Results

    Time frame: Baseline to Week 32

    Number of participants with any grade 3 or 4 treatment-emergent laboratory abnormality

Sponsors and collaborators

Lead sponsor

Matthew C. Baker

Other

Collaborators

  • Stanford University

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Oct 26, 2020
Registry last updated
Apr 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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