Trial Outcomes & Findings for Zanubrutinib in Patients With IgG4-Related Disease (NCT NCT04602598)

NCT ID: NCT04602598

Last Updated: 2026-04-01

Results Overview

To demonstrate that zanubrutinib treatment reduces the volume of the lacrimal glands on PET-MRI at Week 24 compared to Baseline.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2026-04-01

Participant Flow

Participant milestones

Participant milestones
Measure
Zanubrutinib
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Overall Study
STARTED
10
Overall Study
Completed Week 12 Imaging
8
Overall Study
Completed Week 24 Imaging
7
Overall Study
COMPLETED
7
Overall Study
NOT COMPLETED
3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Zanubrutinib in Patients With IgG4-Related Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Zanubrutinib
n=10 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Age, Continuous
58.2 years
STANDARD_DEVIATION 11.4 • n=5 Participants
Age, Customized
<50 years
3 Participants
n=5 Participants
Age, Customized
>=50 years
7 Participants
n=5 Participants
Sex: Female, Male
Female
3 Participants
n=5 Participants
Sex: Female, Male
Male
7 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
9 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race/Ethnicity, Customized
Asian
6 Participants
n=5 Participants
Race/Ethnicity, Customized
Black
1 Participants
n=5 Participants
Race/Ethnicity, Customized
White
2 Participants
n=5 Participants
Race/Ethnicity, Customized
Other
1 Participants
n=5 Participants
Region of Enrollment
United States
10 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 24.

To demonstrate that zanubrutinib treatment reduces the volume of the submandibular glands on PET-MRI at week 24 compared to Baseline.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Volume of the Submandibular Glands on PET-MRI
Week 24
9.34 cm^3
Standard Deviation 4.80
Volume of the Submandibular Glands on PET-MRI
Change from Baseline at Week 24
-3.37 cm^3
Standard Deviation 2.40
Volume of the Submandibular Glands on PET-MRI
Baseline
12.7 cm^3
Standard Deviation 5.78

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 24.

To demonstrate that zanubrutinib treatment reduces the volume of the lacrimal glands on PET-MRI at Week 24 compared to Baseline.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Volume of the Lacrimal Glands on PET-MRI
Baseline
2.59 cm^3
Standard Deviation 2.18
Volume of the Lacrimal Glands on PET-MRI
Week 24
1.17 cm^3
Standard Deviation 0.520
Volume of the Lacrimal Glands on PET-MRI
Change from Baseline at Week 24
-1.42 cm^3
Standard Deviation 1.76

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or 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.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
FDG Avidity (SUVmax) of the Submandibular Glands on PET
Week 24
3.27 kg/L
Standard Deviation 1.05
FDG Avidity (SUVmax) of the Submandibular Glands on PET
Change from Baseline at Week 24
-2.06 kg/L
Standard Deviation 3.41
FDG Avidity (SUVmax) of the Submandibular Glands on PET
Change from Baseline at Week 12
-1.91 kg/L
Standard Deviation 3.14
FDG Avidity (SUVmax) of the Submandibular Glands on PET
Baseline
5.33 kg/L
Standard Deviation 3.77
FDG Avidity (SUVmax) of the Submandibular Glands on PET
Week 12
3.42 kg/L
Standard Deviation 1.26

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

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

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
FDG Avidity (SUVmax) of the Lacrimal Glands on PET
Baseline
5.52 kg/L
Standard Deviation 2.48
FDG Avidity (SUVmax) of the Lacrimal Glands on PET
Week 12
3.37 kg/L
Standard Deviation 1.18
FDG Avidity (SUVmax) of the Lacrimal Glands on PET
Change from Baseline at Week 12
-2.15 kg/L
Standard Deviation 2.45
FDG Avidity (SUVmax) of the Lacrimal Glands on PET
Week 24
3.23 kg/L
Standard Deviation 1.27
FDG Avidity (SUVmax) of the Lacrimal Glands on PET
Change from Baseline at Week 24
-2.29 kg/L
Standard Deviation 2.90

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Total Metabolic Lesion Volume (tMLV) of Lacrimal Glands, Submandibular Glands, Parotid Glands, and Lymph Notes on PET
Baseline
24.3 cm^3
Standard Deviation 20.6
Change in Total Metabolic Lesion Volume (tMLV) of Lacrimal Glands, Submandibular Glands, Parotid Glands, and Lymph Notes on PET
Week 12
5.19 cm^3
Standard Deviation 2.10
Change in Total Metabolic Lesion Volume (tMLV) of Lacrimal Glands, Submandibular Glands, Parotid Glands, and Lymph Notes on PET
Change from Baseline at Week 12
-19.2 cm^3
Standard Deviation 20.5
Change in Total Metabolic Lesion Volume (tMLV) of Lacrimal Glands, Submandibular Glands, Parotid Glands, and Lymph Notes on PET
Week 24
3.64 cm^3
Standard Deviation 2.56
Change in Total Metabolic Lesion Volume (tMLV) of Lacrimal Glands, Submandibular Glands, Parotid Glands, and Lymph Notes on PET
Change from Baseline at Week 24
-20.7 cm^3
Standard Deviation 22.4

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Total Lesion Glycolysis (TLG) of Submandibular and/or Lacrimal Glands on PET
Baseline
103 grams
Standard Deviation 92.1
Change in Total Lesion Glycolysis (TLG) of Submandibular and/or Lacrimal Glands on PET
Week 12
16.1 grams
Standard Deviation 7.54
Change in Total Lesion Glycolysis (TLG) of Submandibular and/or Lacrimal Glands on PET
Change from Baseline at Week 12
-86.7 grams
Standard Deviation 91.3
Change in Total Lesion Glycolysis (TLG) of Submandibular and/or Lacrimal Glands on PET
Week 24
11.2 grams
Standard Deviation 9.91
Change in Total Lesion Glycolysis (TLG) of Submandibular and/or Lacrimal Glands on PET
Change from Baseline at Week 24
-91.6 grams
Standard Deviation 98.5

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or 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.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Submandibular Glands on MRI
Change from Baseline at Week 12 (architecture)
0.125 score on a scale
Standard Deviation 0.342
Change in Submandibular Glands on MRI
Week 24 (architecture)
1.38 score on a scale
Standard Deviation 0.806
Change in Submandibular Glands on MRI
Change from Baseline at Week 24 (architecture)
0.250 score on a scale
Standard Deviation 0.683
Change in Submandibular Glands on MRI
Baseline (saliography)
1.00 score on a scale
Standard Deviation 0
Change in Submandibular Glands on MRI
Week 12 (saliography)
1.00 score on a scale
Standard Deviation 0
Change in Submandibular Glands on MRI
Change from Baseline at Week 12 (sialography)
0 score on a scale
Standard Deviation 0
Change in Submandibular Glands on MRI
Week 24 (sialography)
1.00 score on a scale
Standard Deviation 0
Change in Submandibular Glands on MRI
Baseline (architecture)
1.13 score on a scale
Standard Deviation 0.500
Change in Submandibular Glands on MRI
Week 12 (architecture)
1.25 score on a scale
Standard Deviation 0.577
Change in Submandibular Glands on MRI
Change from Baseline at Week 24 (sialography)
0 score on a scale
Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or 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.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Parotid Glands on MRI
Baseline (architecture)
2.13 score on a scale
Standard Deviation 0.957
Change in Parotid Glands on MRI
Week 12 (architecture)
1.63 score on a scale
Standard Deviation 0.719
Change in Parotid Glands on MRI
Change from Baseline at Week 12 (architecture)
-0.500 score on a scale
Standard Deviation 0.730
Change in Parotid Glands on MRI
Week 24 (architecture)
1.63 score on a scale
Standard Deviation 0.719
Change in Parotid Glands on MRI
Change from Baseline at Week 24 (architecture)
-0.500 score on a scale
Standard Deviation 0.730
Change in Parotid Glands on MRI
Baseline (sialography)
1.13 score on a scale
Standard Deviation 0.342
Change in Parotid Glands on MRI
Week 12 (sialography)
1.13 score on a scale
Standard Deviation 0.342
Change in Parotid Glands on MRI
Change from Baseline at Week 12 (sialography)
0 score on a scale
Standard Deviation 0
Change in Parotid Glands on MRI
Week 24 (sialography)
1.13 score on a scale
Standard Deviation 0.342
Change in Parotid Glands on MRI
Change from Baseline at Week 24 (sialography)
0 score on a scale
Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

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

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Lacrimal Glands on MRI
Baseline
2.13 score on a scale
Standard Deviation 1.09
Change in Lacrimal Glands on MRI
Week 12
2.50 score on a scale
Standard Deviation 0.894
Change in Lacrimal Glands on MRI
Change from Baseline at Week 12
0.375 score on a scale
Standard Deviation 0.500
Change in Lacrimal Glands on MRI
Week 24
2.69 score on a scale
Standard Deviation 0.946
Change in Lacrimal Glands on MRI
Change from Baseline at Week 24
0.563 score on a scale
Standard Deviation 0.814

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in the Volume of the Parotid Glands on PET/MRI
Baseline
44.6 cm^3
Standard Deviation 14.6
Change in the Volume of the Parotid Glands on PET/MRI
Week 12
39.6 cm^3
Standard Deviation 11.6
Change in the Volume of the Parotid Glands on PET/MRI
Change from Baseline at Week 12
-5.07 cm^3
Standard Deviation 5.04
Change in the Volume of the Parotid Glands on PET/MRI
Week 24
38 cm^3
Standard Deviation 11.7
Change in the Volume of the Parotid Glands on PET/MRI
Change from Baseline at Week 24
-6.66 cm^3
Standard Deviation 5.04

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in the Volume of the Submandibular Glands on PET/MRI
Baseline
12.7 cm^3
Standard Deviation 5.78
Change in the Volume of the Submandibular Glands on PET/MRI
Week 12
10.0 cm^3
Standard Deviation 4.97
Change in the Volume of the Submandibular Glands on PET/MRI
Change from Baseline at Week 12
-2.69 cm^3
Standard Deviation 2.35

SECONDARY outcome

Timeframe: Baseline, and Week 12

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in the Volume of the Lacrimal Glands on PET/MRI
Baseline
2.59 cm^3
Standard Deviation 2.18
Change in the Volume of the Lacrimal Glands on PET/MRI
Week 12
1.50 cm^3
Standard Deviation 0.89
Change in the Volume of the Lacrimal Glands on PET/MRI
Change from Baseline at Week 12
-1.09 cm^3
Standard Deviation 1.38

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in the Volume of the Parotid Glands on PET/MRI
Baseline
44.6 cm^3
Standard Deviation 14.6
Change in the Volume of the Parotid Glands on PET/MRI
Change from Baseline at Week 12
-5.07 cm^3
Standard Deviation 5.04
Change in the Volume of the Parotid Glands on PET/MRI
Week 24
38 cm^3
Standard Deviation 11.7
Change in the Volume of the Parotid Glands on PET/MRI
Change from Baseline at Week 24
-6.66 cm^3
Standard Deviation 5.04
Change in the Volume of the Parotid Glands on PET/MRI
Week 12
39.6 cm^3
Standard Deviation 11.6

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Serum IgG4 Level
Baseline
643 mg/dL
Standard Deviation 567
Change in Serum IgG4 Level
Week 12
342 mg/dL
Standard Deviation 305
Change in Serum IgG4 Level
Change from Baseline at Week 12
-301 mg/dL
Standard Deviation 278
Change in Serum IgG4 Level
Week 24
226 mg/dL
Standard Deviation 179
Change in Serum IgG4 Level
Change from Baseline at Week 24
-413 mg/dL
Standard Deviation 443

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

Change in percentage of CD19+ B cells in blood

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Plasmablast Count
Baseline
17.8 percentage of cells
Standard Deviation 25.2
Change in Plasmablast Count
Week 12
0.175 percentage of cells
Standard Deviation 0.205
Change in Plasmablast Count
Change from Baseline at Week 12
-17.6 percentage of cells
Standard Deviation 25.1
Change in Plasmablast Count
Week 24
0.213 percentage of cells
Standard Deviation 0.259
Change in Plasmablast Count
Change from Baseline at Week 24
-19.6 percentage of cells
Standard Deviation 26.5

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

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

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Absolute Regulatory B Cell Count
Baseline
3.03 percentage of cells
Standard Deviation 2.53
Change in Absolute Regulatory B Cell Count
Week 12
0.538 percentage of cells
Standard Deviation 1.03
Change in Absolute Regulatory B Cell Count
Change from Baseline at Week 12
-2.49 percentage of cells
Standard Deviation 2.40
Change in Absolute Regulatory B Cell Count
Week 24
0.450 percentage of cells
Standard Deviation 0.404
Change in Absolute Regulatory B Cell Count
Change from Baseline at Week 24
-2.58 percentage of cells
Standard Deviation 2.39

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or 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.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in the IgG4-RD Responder Index
Baseline
6.63 units on a scale
Standard Deviation 0.916
Change in the IgG4-RD Responder Index
Week 12
2.38 units on a scale
Standard Deviation 2.07
Change in the IgG4-RD Responder Index
Change from Baseline at Week 12
-4.25 units on a scale
Standard Deviation 2.49
Change in the IgG4-RD Responder Index
Week 24
2.00 units on a scale
Standard Deviation 2.20
Change in the IgG4-RD Responder Index
Change from Baseline at Week 24
-4.63 units on a scale
Standard Deviation 2.62

SECONDARY outcome

Timeframe: Week 12 to Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

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

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Proportion of Patients With no Disease Flares
7 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or 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)

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Total Salivary Grey Scale Ultrasound Score (TUS)
Baseline
5.3 score on a scale
Standard Deviation 3.8
Change in Total Salivary Grey Scale Ultrasound Score (TUS)
Week 12
4.4 score on a scale
Standard Deviation 3.0
Change in Total Salivary Grey Scale Ultrasound Score (TUS)
Change from Baseline at Week 12
-0.88 score on a scale
Standard Deviation 1.25
Change in Total Salivary Grey Scale Ultrasound Score (TUS)
Week 24
3.5 score on a scale
Standard Deviation 1.9
Change in Total Salivary Grey Scale Ultrasound Score (TUS)
Change from Baseline at Week 24
-1.75 score on a scale
Standard Deviation 2.19

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or 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)

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Highest Score Among the Salivary Glands for the Grey Scale Ultrasound Score (HSUS)
Baseline
2.3 score on a scale
Standard Deviation 0.71
Change in Highest Score Among the Salivary Glands for the Grey Scale Ultrasound Score (HSUS)
Week 12
1.9 score on a scale
Standard Deviation 0.84
Change in Highest Score Among the Salivary Glands for the Grey Scale Ultrasound Score (HSUS)
Change from Baseline at Week 12
-0.38 score on a scale
Standard Deviation 0.52
Change in Highest Score Among the Salivary Glands for the Grey Scale Ultrasound Score (HSUS)
Week 24
1.6 score on a scale
Standard Deviation 0.74
Change in Highest Score Among the Salivary Glands for the Grey Scale Ultrasound Score (HSUS)
Change from Baseline at Week 24
-0.63 score on a scale
Standard Deviation 0.52

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or 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)

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Glandular Inflammation Total Ultrasound Score (iTUS)
Baseline
7.4 score on a scale
Standard Deviation 2.7
Change in Glandular Inflammation Total Ultrasound Score (iTUS)
Week 12
6.4 score on a scale
Standard Deviation 1.6
Change in Glandular Inflammation Total Ultrasound Score (iTUS)
Change from Baseline at Week 12
-1.00 score on a scale
Standard Deviation 1.77
Change in Glandular Inflammation Total Ultrasound Score (iTUS)
Week 24
5.3 score on a scale
Standard Deviation 1.5
Change in Glandular Inflammation Total Ultrasound Score (iTUS)
Change from Baseline at Week 24
-2.13 score on a scale
Standard Deviation 2.70

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or 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)

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Highest Score Among the Salivary Glands for the Glandular Inflammation Ultrasound Score (iHSUS)
Baseline
2.4 score on a scale
Standard Deviation 0.92
Change in Highest Score Among the Salivary Glands for the Glandular Inflammation Ultrasound Score (iHSUS)
Week 12
2.1 score on a scale
Standard Deviation 0.84
Change in Highest Score Among the Salivary Glands for the Glandular Inflammation Ultrasound Score (iHSUS)
Change from Baseline at Week 12
-0.25 score on a scale
Standard Deviation 0.46
Change in Highest Score Among the Salivary Glands for the Glandular Inflammation Ultrasound Score (iHSUS)
Week 24
1.8 score on a scale
Standard Deviation 0.71
Change in Highest Score Among the Salivary Glands for the Glandular Inflammation Ultrasound Score (iHSUS)
Change from Baseline at Week 24
-0.63 score on a scale
Standard Deviation 0.74

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

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

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Physician Global Assessment of Disease
Change from Baseline at Week 24
-51.0 score on a scale
Standard Deviation 28.3
Change in Physician Global Assessment of Disease
Baseline
68.4 score on a scale
Standard Deviation 12.7
Change in Physician Global Assessment of Disease
Week 12
21.4 score on a scale
Standard Deviation 29.4
Change in Physician Global Assessment of Disease
Change from Baseline at Week 12
-47.0 score on a scale
Standard Deviation 27.8
Change in Physician Global Assessment of Disease
Week 24
17.4 score on a scale
Standard Deviation 29.3

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

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

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Patient Global Assessment of Disease
Baseline
52.4 score on a scale
Standard Deviation 19.6
Change in Patient Global Assessment of Disease
Week 12
38.4 score on a scale
Standard Deviation 30.4
Change in Patient Global Assessment of Disease
Change from Baseline at Week 12
-14.0 score on a scale
Standard Deviation 27.1
Change in Patient Global Assessment of Disease
Week 24
31.0 score on a scale
Standard Deviation 25.8
Change in Patient Global Assessment of Disease
Change from Baseline at Week 24
-21.4 score on a scale
Standard Deviation 26.6

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24

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

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in VAS for Ocular Symptoms - Dryness
Baseline
47.6 score on a scale
Standard Deviation 25.3
Change in VAS for Ocular Symptoms - Dryness
Week 12
31.9 score on a scale
Standard Deviation 20.9
Change in VAS for Ocular Symptoms - Dryness
Change from Baseline at Week 12
-15.8 score on a scale
Standard Deviation 28.9
Change in VAS for Ocular Symptoms - Dryness
Week 24
21.5 score on a scale
Standard Deviation 15.1
Change in VAS for Ocular Symptoms - Dryness
Change from Baseline at Week 24
-26.1 score on a scale
Standard Deviation 32.7

SECONDARY outcome

Timeframe: Baseline, Week 12, Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or 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.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in VAS for Dryness Symptoms
Baseline
47.6 score on a scale
Standard Deviation 25.3
Change in VAS for Dryness Symptoms
Week 12
31.9 score on a scale
Standard Deviation 20.9
Change in VAS for Dryness Symptoms
Change from Baseline at Week 12
-15.8 score on a scale
Standard Deviation 28.9
Change in VAS for Dryness Symptoms
Week 24
21.5 score on a scale
Standard Deviation 15.1
Change in VAS for Dryness Symptoms
Change from Baseline at Week 24
-26.1 score on a scale
Standard Deviation 32.7

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

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

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in FACIT-F Fatigue Score
Baseline
38.9 score on a scale
Standard Deviation 14.0
Change in FACIT-F Fatigue Score
Week 12
41.6 score on a scale
Standard Deviation 9.12
Change in FACIT-F Fatigue Score
Change from Baseline at Week 12
2.75 score on a scale
Standard Deviation 10.4
Change in FACIT-F Fatigue Score
Week 24
43.3 score on a scale
Standard Deviation 5.80
Change in FACIT-F Fatigue Score
Change from Baseline at Week 24
4.38 score on a scale
Standard Deviation 11.6

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

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

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in RAND Short Form-36
Baseline
85.6 score on a scale
Standard Deviation 15.5
Change in RAND Short Form-36
Week 12
78.8 score on a scale
Standard Deviation 30.3
Change in RAND Short Form-36
Change from Baseline at Week 12
-6.88 score on a scale
Standard Deviation 23.0
Change in RAND Short Form-36
Week 24
78.1 score on a scale
Standard Deviation 29.1
Change in RAND Short Form-36
Change from Baseline at Week 24
-7.50 score on a scale
Standard Deviation 21.9

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

Complement component 3 (C3) level in blood

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in C3 Lab
Baseline
116 mg/dL
Standard Deviation 29.0
Change in C3 Lab
Week 12
114 mg/dL
Standard Deviation 16.7
Change in C3 Lab
Change from Baseline at Week 12
1.86 mg/dL
Standard Deviation 22.3
Change in C3 Lab
Week 24
121 mg/dL
Standard Deviation 23.7
Change in C3 Lab
Change from Baseline at Week 24
6.43 mg/dL
Standard Deviation 21.4

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

Complement component 4 (C4) level in blood

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in C4 Lab
Baseline
28.6 mg/dL
Standard Deviation 14.1
Change in C4 Lab
Week 12
31.5 mg/dL
Standard Deviation 8.93
Change in C4 Lab
Change from Baseline at Week 12
2.88 mg/dL
Standard Deviation 9.51
Change in C4 Lab
Week 24
31.0 mg/dL
Standard Deviation 8.00
Change in C4 Lab
Change from Baseline at Week 24
2.00 mg/dL
Standard Deviation 11.6

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in Total IgG Lab
Baseline
1610 mg/dL
Standard Deviation 578
Change in Total IgG Lab
Week 12
1240 mg/dL
Standard Deviation 286
Change in Total IgG Lab
Change from Baseline at Week 12
-368 mg/dL
Standard Deviation 345
Change in Total IgG Lab
Week 24
1200 mg/dL
Standard Deviation 316
Change in Total IgG Lab
Change from Baseline at Week 24
-395 mg/dL
Standard Deviation 570

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in IgE Lab
Week 12
1230 kU/L
Standard Deviation 1070
Change in IgE Lab
Change from Baseline at Week 12
672 kU/L
Standard Deviation 965
Change in IgE Lab
Week 24
1280 kU/L
Standard Deviation 1010
Change in IgE Lab
Change from Baseline at Week 24
544 kU/L
Standard Deviation 817
Change in IgE Lab
Baseline
562 kU/L
Standard Deviation 396

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in IgG1 Lab
Baseline
572 mg/dL
Standard Deviation 106
Change in IgG1 Lab
Week 12
491 mg/dL
Standard Deviation 67.0
Change in IgG1 Lab
Change from Baseline at Week 12
-80.8 mg/dL
Standard Deviation 65.2
Change in IgG1 Lab
Week 24
505 mg/dL
Standard Deviation 125
Change in IgG1 Lab
Change from Baseline at Week 24
-71.2 mg/dL
Standard Deviation 109

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

Change in erythrocyte sedimentation rate (ESR)

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in ESR Lab
Baseline
20.4 mm/hr
Standard Deviation 19.7
Change in ESR Lab
Week 12
9.00 mm/hr
Standard Deviation 5.26
Change in ESR Lab
Change from Baseline at Week 12
-11.4 mm/hr
Standard Deviation 15.9
Change in ESR Lab
Week 24
8.75 mm/hr
Standard Deviation 3.85
Change in ESR Lab
Change from Baseline at Week 24
-12.9 mm/hr
Standard Deviation 18.6

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Per-Protocol Analysis Set: all subjects who were enrolled in the study, received at least 1 dose of study drug, and had a follow-up imaging study at Week 12 and/or Week 24.

Change in serum C-reactive protein (CRP) level

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=8 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Change in CRP Lab
Baseline
0.313 mg/dL
Standard Deviation 0.0354
Change in CRP Lab
Week 12
0.313 mg/dL
Standard Deviation 0.0354
Change in CRP Lab
Change from Baseline at Week 12
0 mg/dL
Standard Deviation 0.0535
Change in CRP Lab
Week 24
0.300 mg/dL
Standard Deviation 0
Change in CRP Lab
Change from Baseline at Week 24
-0.0143 mg/dL
Standard Deviation 0.0378

SECONDARY outcome

Timeframe: Baseline to Week 32

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

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=10 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Incidence of Safety Parameters Including Adverse Events
TEAE
10 Participants
Incidence of Safety Parameters Including Adverse Events
TEAE with Grade 3 or Higher
2 Participants
Incidence of Safety Parameters Including Adverse Events
TEAE Related to Study Drug
8 Participants
Incidence of Safety Parameters Including Adverse Events
TEAE Related to Study Drug with Grade 3 or Higher
1 Participants
Incidence of Safety Parameters Including Adverse Events
TE Serious AE
1 Participants
Incidence of Safety Parameters Including Adverse Events
TE Serious AE Related to Study Drug
0 Participants
Incidence of Safety Parameters Including Adverse Events
TEAE Leading to Premature Discontinuation of Study Drug
2 Participants
Incidence of Safety Parameters Including Adverse Events
TEAE Leading to Premature Discontinuation of Study
2 Participants

SECONDARY outcome

Timeframe: Baseline to Week 32

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

Outcome measures

Outcome measures
Measure
Zanubrutinib
n=10 Participants
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Incidence of Safety Parameters Including Abnormal Laboratory Results
2 Participants

Adverse Events

Zanubrutinib

Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Zanubrutinib
n=10 participants at risk
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Infections and infestations
COVID-19
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)

Other adverse events

Other adverse events
Measure
Zanubrutinib
n=10 participants at risk
Zanubrutinib orally at a dose of 80mg BID for 24 weeks
Cardiac disorders
Atrial fibrillation
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Vascular disorders
Hypertension
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Infections and infestations
Upper respiratory tract infection
40.0%
4/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Blood and lymphatic system disorders
Neutrophil count decreased
20.0%
2/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Infections and infestations
COVID-19
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Blood and lymphatic system disorders
Leukocytosis
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Blood and lymphatic system disorders
Eosinophilia
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Blood and lymphatic system disorders
Anemia
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Renal and urinary disorders
Hematuria
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Skin and subcutaneous tissue disorders
Rash
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Skin and subcutaneous tissue disorders
Urticaria
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Skin and subcutaneous tissue disorders
Bullous pemphigoid
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Skin and subcutaneous tissue disorders
Petechiae
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Infections and infestations
Cellulitis
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Musculoskeletal and connective tissue disorders
Bursitis
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Ear and labyrinth disorders
Otitis externa
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Infections and infestations
Sinusitis
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Infections and infestations
Sinus infection
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Gastrointestinal disorders
Diarrhea
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Gastrointestinal disorders
Oral lesion
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Musculoskeletal and connective tissue disorders
Soft tissue mass
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Renal and urinary disorders
Acute kidney injury
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
General disorders
Hypernatremia
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)
Nervous system disorders
Parkinsonism
10.0%
1/10 • Up to 32 weeks (24 weeks treatment plus 8 weeks follow-up)

Additional Information

Matthew Baker

Stanford University, School of Medicine, Division of Immunology & Rheumatology

Phone: 6504970744

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place