Zanubrutinib in Patients With IgG4-Related Disease

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

Study Overview

• Status: Recruiting
• Conditions: IgG4 Related Disease
• Intervention / Treatment: Drug: Zanubrutinib 80 MG

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 Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Matthew C Baker, MD; Phone Number: 650-497-0774; Email: mbaker13@stanford.edu
• Study Contact Backup: Name: Angie R Aberia, BA; Phone Number: 650-723-8516; Email: aaberia@stanford.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University
      • Contact: Matthew C Baker, MD, MS
      • Principal Investigator: Matthew C Baker, MD, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zanubrutinib; Zanubrutinib orally at a dose of 80mg BID for 24 weeks	Drug: Zanubrutinib 80 MG; Zanubrutinib 80 MG for 24 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Matthew C. Baker
• Collaborators: Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: October 20, 2020
• First Submitted That Met QC Criteria: October 20, 2020
• First Posted (Actual): October 26, 2020

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Immunoglobulin G4-Related Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Zanubrutinib
• Other Study ID Numbers: 58497

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No