Study to Assess Safety and Efficacy of Filgotinib, Lanrap... | NCT03100942 | Trialant
NCT03100942
Sponsor
Gilead Sciences
Status
Completed
Last Update Posted
Oct 23, 2020Actual
Enrollment
152Actual
Phase
Phase 2
Conditions
Sjogren's Syndrome
Interventions
Lanraplenib
Filgotinib
Tirabrutinib
Lanraplenib placebo
Filgotinib placebo
Tirabrutinib placebo
Countries
United States
Poland
Spain
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT03100942
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
GS-US-445-4189
Secondary IDs
ID
Type
Description
Link
2016-003558-34
EudraCT Number
Brief Title
Study to Assess Safety and Efficacy of Filgotinib, Lanraplenib and Tirabrutinib in Adults With Active Sjogren's Syndrome
Official Title
A Randomized, Phase 2, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of Filgotinib, GS-9876 and GS-4059 in Adult Subjects With Active Sjogren's Syndrome
Acronym
Not provided
Organization
Gilead SciencesINDUSTRY
Status Module
Record Verification Date
Oct 2020
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
May 1, 2017Actual
Primary Completion Date
Jan 10, 2019Actual
Completion Date
Oct 2, 2019Actual
First Submitted Date
Mar 31, 2017
First Submission Date that Met QC Criteria
Mar 31, 2017
First Posted Date
Apr 4, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Dec 19, 2019
Results First Submitted that Met QC Criteria
Jan 17, 2020
Results First Posted Date
Jan 22, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 1, 2020
Last Update Posted Date
Oct 23, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Gilead SciencesINDUSTRY
Collaborators
Name
Class
Lakefront Biotherapeutics NV
INDUSTRY
Ono Pharmaceutical Co., Ltd.
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The primary objective of this study is to assess the efficacy of filgotinib, lanraplenib, and tirabrutinib in adults with active Sjogren's Syndrome (SjS).
Detailed Description
Not provided
Conditions Module
Conditions
Sjogren's Syndrome
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
152Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Lanraplenib
Experimental
Lanraplenib + filgotinib placebo + tirabrutinib placebo for up to 49.4 weeks.
Drug: Lanraplenib
Drug: Filgotinib placebo
Drug: Tirabrutinib placebo
Filgotinib
Experimental
Filgotinib + lanraplenib placebo + tirabrutinib placebo for up to 50.4 weeks.
Drug: Filgotinib
Drug: Lanraplenib placebo
Drug: Tirabrutinib placebo
Tirabrutinib
Experimental
Tirabrutinib + filgotinib placebo + lanraplenib placebo for up to 50.3 weeks.
Drug: Tirabrutinib
Drug: Lanraplenib placebo
Drug: Filgotinib placebo
Placebo, then active treatment
Placebo Comparator
Filgotinib placebo + lanraplenib placebo + tirabrutinib placebo for 24 weeks. Following completion of the Week 24 assessments and procedures, participants will be rerandomized 1:1:1, in a blinded fashion and receive either of the following study drugs through Week 48:
Percentage of Participants Fulfilling Protocol-Specified Response Criteria at Week 12, as Compared to Baseline
Response was defined as: Improvement ≥ 20% in ≥ 3 of 5 participant-reported Sjogren's syndrome (SjS) related visual analogue score (VAS) measures (participant's assessment of global disease, pain, oral dryness, ocular dryness and fatigue), with no increase defined as > 30 mm from baseline (Day 1) in any of the above 5 VAS measures, AND either ≥ 20% improvement in high sensitivity C-reactive protein (hsCRP) (if hsCRP ≥ 1.5 x upper limit of normal [ULN] on Day 1) or no increase in hsCRP to ≥ 1.5 x ULN (if hsCRP < 1.5 x ULN on Day 1).
Week 12
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) at Week 12
The ESSDAI is a physician-administered tool designed to measure disease activity. It consists of 12 organ-specific 'domains' contributing to disease activity associated with the participant's Sjogren's Syndrome only (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, biological). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. Overall score (ranges from 0 (no activity) to 123 (worst activity)) is calculated as sum of all individual weighted domain scores. A negative change from baseline value indicates improvement.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Key Inclusion Criteria:
Diagnosed with primary or secondary SjS according to the 2002 American European Consensus Group (AECG) classification
Active SjS as defined by an European League Against Rheumatism (EULAR) Sjogren's syndrome disease activity index (ESSDAI) ≥ 5
Seropositivity for antibodies to SjS-associated antigens A and/or B (anti-SSA or anti-SSB)
Key Exclusion Criteria:
Concurrent treatment with any biologic disease modifying antirheumatic drug (bDMARD) (prior bDMARD treatment allowed with appropriate washout as per study protocol)
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Price E, Bombardieri M, Kivitz A, Matzkies F, Gurtovaya O, Pechonkina A, Jiang W, Downie B, Mathur A, Mozaffarian A, Mozaffarian N, Gottenberg JE. Safety and efficacy of filgotinib, lanraplenib and tirabrutinib in Sjogren's syndrome: a randomized, phase 2, double-blind, placebo-controlled study. Rheumatology (Oxford). 2022 Nov 28;61(12):4797-4808. doi: 10.1093/rheumatology/keac167.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
No
Description
Not provided
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
348 participants were screened.
Recruitment Details
Participants were enrolled at study sites in the United States and Europe. The first participant was screened on 01 May 2017. The last study visit occurred on 02 October 2019.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Lanraplenib
Lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for up to 49.4 weeks.
FG001
Filgotinib
Filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for up to 50.4 weeks
Periods
Title
Milestones
Reasons Not Completed
Randomized Treatment Period
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jul 12, 2018
Nov 18, 2019
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
GS-9876
Filgotinib
Drug
1 x 200 mg tablet administered orally once daily
Filgotinib
Placebo, then active treatment
GS-6034
Tirabrutinib
Drug
1 x 40 mg tablet administered orally once daily
Placebo, then active treatment
Tirabrutinib
GS-4059
Lanraplenib placebo
Drug
1 x tablet administered orally once daily
Filgotinib
Placebo, then active treatment
Tirabrutinib
Filgotinib placebo
Drug
1 x tablet administered orally once daily
Lanraplenib
Placebo, then active treatment
Tirabrutinib
Tirabrutinib placebo
Drug
1 x tablet administered orally once daily
Filgotinib
Lanraplenib
Placebo, then active treatment
Baseline; Week 12
Change From Baseline in EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) at Week 12
The ESSPRI is a participant-reported questionnaire to assess subjective participant symptoms and includes 3 domains (dryness, pain, and fatigue). Each domain is scored on scale of 0-10 (0 = no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight. Minimum score can be 0 and maximum score can be 10. A negative change from baseline value indicates improvement.
Baseline; Week 12
Change From Baseline in ESSDAI at Week 24
The ESSDAI is a physician-administered tool designed to measure disease activity. It consists of 12 organ-specific 'domains' contributing to disease activity associated with the participant's Sjogren's Syndrome only (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, biological). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. Overall score (ranges from 0 (no activity) to 123 (worst activity)) is calculated as sum of all individual weighted domain scores. A negative change from baseline value indicates improvement.
Baseline; Week 24
Change From Baseline in ESSPRI at Week 24
The ESSPRI is a participant-reported questionnaire to assess subjective participant symptoms and includes 3 domains (dryness, pain, and fatigue). Each domain is scored on scale of 0-10 (0 = no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight. Minimum score can be 0 and maximum score can be 10. A negative change from baseline value indicates improvement.
Baseline; Week 24
Phoenix
Arizona
85032
United States
Medvin Clinical Research
Covina
California
91723
United States
Inland Rheumatology Clinical Trials, Inc.
Upland
California
91786
United States
Denver Arthritis Clinic
Denver
Colorado
80230
United States
Clinical Research of West Florida, Inc.
Clearwater
Florida
33765
United States
Omega Research Consultants LLC
DeBary
Florida
32713
United States
Center for Rheumatology Immunology and Arthritis
Fort Lauderdale
Florida
33309
United States
Suncoast Clinical Research, Inc.
New Port Richey
Florida
34668
United States
IRIS Research and Development, LLC
Plantation
Florida
33324
United States
North Georgia Rheumatology Group, PC
Lawrenceville
Georgia
30046
United States
Springfield Clinic
Springfield
Illinois
62703
United States
Center for Arthritis & Osteoporosis
Elizabethtown
Kentucky
42701
United States
June DO, PC
Lansing
Michigan
48910
United States
North Mississippi Medical Clinics, Inc. - Clinical Research
Tupelo
Mississippi
38801
United States
Clayton Medical Associates
St Louis
Missouri
63117
United States
Physician Research Collaboration, LLC
Lincoln
Nebraska
68516
United States
Albuquerque Clinical Trials
Albuquerque
New Mexico
87102
United States
Joint and Muscle Research Institute
Charlotte
North Carolina
28204
United States
Cape Fear Arthritis Care, PLLC
Leland
North Carolina
28451
United States
PMG Research of Salisbury
Salisbury
North Carolina
28144
United States
East Penn Rheumatology Associates, P.C.
Bethlehem
Pennsylvania
18015
United States
Altoona Center for Clinical Research
Duncansville
Pennsylvania
16635
United States
Clinical Research Center of Reading, LLC
Wyomissing
Pennsylvania
19610
United States
ClinSearch
Chattanooga
Tennessee
37421
United States
Ramesh C. Gupta, MD
Memphis
Tennessee
38119
United States
Diagnostic Group Integrated Healthcare System, Pllc
Beaumont
Texas
77701
United States
Accurate Clinical Research Inc.
Houston
Texas
77034
United States
Southwest Rheumatology Research
Mesquite
Texas
75150
United States
Trinity Universal Research Associates
Plano
Texas
75024
United States
Arthritis & Osteoporosis Clinic
Waco
Texas
76710
United States
Wasatch Peak Family Practice
Layton
Utah
84041
United States
The Center for Arthritis and Rheumatic Diseases, PC
Participants who received placebo for 24 weeks were re-randomized at the Week 24 visit and received lanraplenib (1 × 30 mg tablet) + filgotinib placebo (1 × tablet) + tirabrutinib placebo (1 × tablet) orally once daily for up to 25.1 weeks.
FG005
Placebo to Filgotinib
Participants who received placebo for 24 weeks were re-randomized at the Week 24 visit and received filgotinib (1 × 200 mg tablet) + lanraplenib placebo (1 × tablet) + tirabrutinib placebo (1 × tablet) orally once daily for up to 24.4 weeks.
FG006
Placebo to Tirabrutinib
Participants who received placebo for 24 weeks were re-randomized at the Week 24 visit and received tirabrutinib (1 × 40 mg tablet) + filgotinib placebo (1 × tablet) + lanraplenib placebo (1 × tablet) orally once daily for up to 24.9 weeks.
FG00038 subjects
FG00138 subjects
FG00239 subjects
FG00337 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
COMPLETED
FG00026 subjects
FG00129 subjects
FG00233 subjects
FG00332 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
NOT COMPLETED
FG00012 subjects
FG0019 subjects
FG0026 subjects
FG0035 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Type
Comment
Reasons
Withdrew Consent
FG0004 subjects
FG0015 subjects
FG0023 subjects
FG0033 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Adverse Event
FG0005 subjects
FG0012 subjects
FG0021 subjects
FG0030 subjects
FG004
Investigator's Discretion
FG0002 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Protocol Violation
FG0000 subjects
FG0011 subjects
FG0021 subjects
FG0031 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Randomized but Didn't Receive Study Drug
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Placebo Arm Re-Randomized
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG00410 subjects
FG00512 subjects
FG00610 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Withdrew Consent
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
The Safety Analysis Set included participants who received at least one dose of study drug.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Lanraplenib
Lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for up to 49.4 weeks.
BG001
Filgotinib
Filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for up to 50.4 weeks.
BG002
Tirabrutinib
Tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet) orally once daily for up to 50.3 weeks.
BG003
Placebo
Participants received filgotinib placebo + lanraplenib placebo + tirabrutinib placebo tablets orally once daily for 24 weeks. At Week 24 Visit, participants were rerandomized 1:1:1, in a blinded fashion and received either of the three experimental study drugs orally once daily through Week 48:
lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet)
filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet)
tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet)
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00037
BG00138
BG00239
BG00336
BG004150
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00056.2± 9.72
BG00152.2± 10.54
BG00255.8± 10.06
BG003
Sex: Female, Male
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
Female
BG00036
BG00138
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0006
BG0014
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Region of Enrollment
Number
participants
No
Title
Denominators
Categories
United States
Title
Measurements
BG00026
BG00127
BG002
European League Against Rheumatism (EULAR) Sjogren's syndrome disease activity index (ESSDAI)
Overall score (ranged from 0 (best) to 123 (worst activity)) was calculated as sum of all individual weighted domain scores. For additional details on this index, please see Outcome Measures# 2 and 4.
Mean
Standard Deviation
Score on a scale
Title
Denominators
Categories
Title
Measurements
BG00010.5± 4.89
BG001
EULAR Sjogren's syndrome patient reported index (ESSPRI)
The ESSPRI is a patient-reported questionnaire to assess subjective patient symptoms and includes 3 domains (dryness, pain, and fatigue). Each domain scored on scale of 0-10 (0 = no symptoms at all and 10 = worst symptoms imaginable), and an overall score is calculated as the mean of the three individual domain scores where all domains carry the same weight. Minimum score can be 0 and maximum score can be 10.
Mean
Standard Deviation
Score on a scale
Title
Denominators
Categories
Title
Measurements
BG0006.6± 1.90
BG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Percentage of Participants Fulfilling Protocol-Specified Response Criteria at Week 12, as Compared to Baseline
Response was defined as: Improvement ≥ 20% in ≥ 3 of 5 participant-reported Sjogren's syndrome (SjS) related visual analogue score (VAS) measures (participant's assessment of global disease, pain, oral dryness, ocular dryness and fatigue), with no increase defined as > 30 mm from baseline (Day 1) in any of the above 5 VAS measures, AND either ≥ 20% improvement in high sensitivity C-reactive protein (hsCRP) (if hsCRP ≥ 1.5 x upper limit of normal [ULN] on Day 1) or no increase in hsCRP to ≥ 1.5 x ULN (if hsCRP < 1.5 x ULN on Day 1).
The Full Analysis Set included all randomized participants who received at least one dose of study drug. Included participants with available data.
Posted
Number
95% Confidence Interval
percentage of participants
Week 12
ID
Title
Description
OG000
Lanraplenib
Lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks
OG001
Filgotinib
Filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks
OG002
Tirabrutinib
Tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet) orally once daily for 48 weeks
OG003
Placebo
Participants received filgotinib placebo + lanraplenib placebo + tirabrutinib placebo tablets orally once daily for 24 weeks. At Week 24 Visit, participants were rerandomized 1:1:1, in a blinded fashion and received either of the three experimental study drugs orally once daily through Week 48:
filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet)
lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet)
tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet)
Units
Counts
Participants
OG00035
OG00137
OG00237
OG003
Title
Denominators
Categories
Title
Measurements
OG00042.9(25.0 to 60.7)
OG00143.2(25.9 to 60.6)
OG00235.1(18.4 to 51.9)
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Cochran-Mantel-Haenszel
0.1597
P-values were obtained from Cochran-Mantel-Haenszel (CMH) test stratified by randomization stratification factors.
Difference in Response Rates
15.6
2-Sided
95
-6.3
37.6
For the analysis of the difference in response rates, the data with missing response values were imputed by multiple imputation method with logistic regression.
Superiority
Secondary
Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) at Week 12
The ESSDAI is a physician-administered tool designed to measure disease activity. It consists of 12 organ-specific 'domains' contributing to disease activity associated with the participant's Sjogren's Syndrome only (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, biological). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. Overall score (ranges from 0 (no activity) to 123 (worst activity)) is calculated as sum of all individual weighted domain scores. A negative change from baseline value indicates improvement.
Participants in the Full Analysis Set were analyzed.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline; Week 12
ID
Title
Description
OG000
Lanraplenib
Lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks
OG001
Filgotinib
Filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks
OG002
Secondary
Change From Baseline in EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) at Week 12
The ESSPRI is a participant-reported questionnaire to assess subjective participant symptoms and includes 3 domains (dryness, pain, and fatigue). Each domain is scored on scale of 0-10 (0 = no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight. Minimum score can be 0 and maximum score can be 10. A negative change from baseline value indicates improvement.
Participants in the Full Analysis Set were analyzed.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline; Week 12
ID
Title
Description
OG000
Lanraplenib
Lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks
OG001
Filgotinib
Filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks
OG002
Tirabrutinib
Tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet) orally once daily for 48 weeks
Secondary
Change From Baseline in ESSDAI at Week 24
The ESSDAI is a physician-administered tool designed to measure disease activity. It consists of 12 organ-specific 'domains' contributing to disease activity associated with the participant's Sjogren's Syndrome only (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, biological). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. Overall score (ranges from 0 (no activity) to 123 (worst activity)) is calculated as sum of all individual weighted domain scores. A negative change from baseline value indicates improvement.
Participants in the Full Analysis Set were analyzed.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline; Week 24
ID
Title
Description
OG000
Lanraplenib
Lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks
OG001
Filgotinib
Filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks
OG002
Tirabrutinib
Secondary
Change From Baseline in ESSPRI at Week 24
The ESSPRI is a participant-reported questionnaire to assess subjective participant symptoms and includes 3 domains (dryness, pain, and fatigue). Each domain is scored on scale of 0-10 (0 = no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight. Minimum score can be 0 and maximum score can be 10. A negative change from baseline value indicates improvement.
Participants in the Full Analysis Set were analyzed.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline; Week 24
ID
Title
Description
OG000
Lanraplenib
Lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks
OG001
Filgotinib
Filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks
OG002
Tirabrutinib
Tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet) orally once daily for 48 weeks
Time Frame
First dose date up to last dose date (Maximum: 50.4 weeks) plus 30 days
Description
The Safety Analysis Set included participants who received at least one dose of study drug.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Lanraplenib
Lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for up to 49.4 weeks.
0
37
3
37
30
37
EG001
Filgotinib
Filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for up to 50.4 weeks.
0
38
5
38
31
38
EG002
Tirabrutinib
Tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet) orally once daily for up to 50.3 weeks.
0
39
1
39
32
39
EG003
Placebo to Lanraplenib
Participants who received placebo for 24 weeks were rerandomized at the Week 24 visit and received lanraplenib (1 × 30 mg tablet) + filgotinib placebo (1 × tablet) + tirabrutinib placebo (1 × tablet) orally once daily for up to 25.1 weeks.
0
10
0
10
10
10
EG004
Placebo to Filgotinib
Participants who received placebo for 24 weeks were rerandomized at the Week 24 visit and received filgotinib (1 × 200 mg tablet) + lanraplenib placebo (1 × tablet) + tirabrutinib placebo (1 × tablet) orally once daily for up to 24.4 weeks.
0
12
1
12
10
12
EG005
Placebo to Tirabrutinib
Participants who received placebo for 24 weeks were rerandomized at the Week 24 visit and received tirabrutinib (1 × 40 mg tablet) + filgotinib placebo (1 × tablet) + lanraplenib placebo (1 × tablet) orally once daily for up to 24.9 weeks.
0
10
0
10
7
10
EG006
Placebo on Placebo Controlled Period
Participants received filgotinib placebo + lanraplenib placebo + tirabrutinib placebo tablets orally once daily for 24 weeks in placebo controlled period.
At Week 24 visit, participants were re-randomized 1:1:1, in a blinded fashion and receive either of the following study drugs through Week 48:
tirabrutinib + filgotinib placebo + lanraplenib placeboy once daily for 24 weeks.
0
36
2
36
23
36
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Acute coronary syndrome
Cardiac disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG0030 affected10 at risk
EG0040 affected12 at risk
EG0050 affected10 at risk
EG0060 affected36 at risk
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0011 affected38 at risk
EG0020 affected39 at risk
EG003
Pancreatitis acute
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0011 affected38 at risk
EG0020 affected39 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0021 affected39 at risk
EG003
Rheumatoid arthritis
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Breast cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Migraine
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0011 affected38 at risk
EG0020 affected39 at risk
EG003
Suicidal ideation
Psychiatric disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0011 affected38 at risk
EG0020 affected39 at risk
EG003
Interstitial lung disease
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0011 affected38 at risk
EG0020 affected39 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0010 affected38 at risk
EG0022 affected39 at risk
EG0030 affected10 at risk
EG0040 affected12 at risk
EG0050 affected10 at risk
EG0060 affected36 at risk
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA 22.0
Systematic Assessment
EG0002 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Lymphopenia
Blood and lymphatic system disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 22.0
Systematic Assessment
EG0002 affected37 at risk
EG0012 affected38 at risk
EG0020 affected39 at risk
EG003
Corneal erosion
Eye disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Vision blurred
Eye disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0011 affected38 at risk
EG0021 affected39 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0011 affected38 at risk
EG0021 affected39 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0023 affected39 at risk
EG003
Dental caries
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0002 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0003 affected37 at risk
EG0013 affected38 at risk
EG0023 affected39 at risk
EG003
Food poisoning
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0011 affected38 at risk
EG0020 affected39 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0021 affected39 at risk
EG003
Lip blister
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0012 affected38 at risk
EG0020 affected39 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0002 affected37 at risk
EG0014 affected38 at risk
EG0022 affected39 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0002 affected37 at risk
EG0013 affected38 at risk
EG0022 affected39 at risk
EG003
Asthenia
General disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0011 affected38 at risk
EG0020 affected39 at risk
EG003
Fatigue
General disorders
MedDRA 22.0
Systematic Assessment
EG0004 affected37 at risk
EG0010 affected38 at risk
EG0023 affected39 at risk
EG003
Pyrexia
General disorders
MedDRA 22.0
Systematic Assessment
EG0003 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Seasonal allergy
Immune system disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0011 affected38 at risk
EG0022 affected39 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0002 affected37 at risk
EG0013 affected38 at risk
EG0021 affected39 at risk
EG003
Conjunctivitis viral
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Fungal skin infection
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Furuncle
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0010 affected38 at risk
EG0021 affected39 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0003 affected37 at risk
EG0012 affected38 at risk
EG0023 affected39 at risk
EG003
Helicobacter infection
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0012 affected38 at risk
EG0020 affected39 at risk
EG003
Influenza
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0010 affected38 at risk
EG0023 affected39 at risk
EG003
Laryngitis
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0002 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0002 affected37 at risk
EG0010 affected38 at risk
EG0021 affected39 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0003 affected37 at risk
EG0016 affected38 at risk
EG0024 affected39 at risk
EG003
Oral herpes
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0002 affected37 at risk
EG0013 affected38 at risk
EG0020 affected39 at risk
EG003
Otitis media
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0011 affected38 at risk
EG0020 affected39 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0012 affected38 at risk
EG0020 affected39 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0012 affected38 at risk
EG0021 affected39 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0002 affected37 at risk
EG0011 affected38 at risk
EG0025 affected39 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0004 affected37 at risk
EG0016 affected38 at risk
EG0029 affected39 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0012 affected38 at risk
EG0024 affected39 at risk
EG003
Vaginal infection
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Viral pharyngitis
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Vulvovaginal mycotic infection
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0022 affected39 at risk
EG003
Arthropod bite
Injury, poisoning and procedural complications
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0012 affected38 at risk
EG0022 affected39 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0012 affected38 at risk
EG0022 affected39 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 22.0
Systematic Assessment
EG0004 affected37 at risk
EG0011 affected38 at risk
EG0022 affected39 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 22.0
Systematic Assessment
EG0004 affected37 at risk
EG0011 affected38 at risk
EG0021 affected39 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Blood potassium increased
Investigations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Light chain analysis increased
Investigations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0021 affected39 at risk
EG003
Liver function test abnormal
Investigations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Transaminases increased
Investigations
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0004 affected37 at risk
EG0014 affected38 at risk
EG0026 affected39 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0011 affected38 at risk
EG0021 affected39 at risk
EG003
Exostosis
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0012 affected38 at risk
EG0022 affected39 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0011 affected38 at risk
EG0020 affected39 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0002 affected37 at risk
EG0010 affected38 at risk
EG0021 affected39 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0011 affected38 at risk
EG0021 affected39 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0012 affected38 at risk
EG0020 affected39 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0013 affected38 at risk
EG0020 affected39 at risk
EG003
Rheumatoid arthritis
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0011 affected38 at risk
EG0020 affected39 at risk
EG003
Temporomandibular joint syndrome
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0011 affected38 at risk
EG0020 affected39 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0003 affected37 at risk
EG0011 affected38 at risk
EG0021 affected39 at risk
EG003
Headache
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0013 affected38 at risk
EG0023 affected39 at risk
EG003
Migraine
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0011 affected38 at risk
EG0020 affected39 at risk
EG003
Sciatica
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0013 affected38 at risk
EG0020 affected39 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0011 affected38 at risk
EG0022 affected39 at risk
EG003
Allergic sinusitis
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0011 affected38 at risk
EG0023 affected39 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0021 affected39 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0012 affected38 at risk
EG0020 affected39 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0012 affected38 at risk
EG0022 affected39 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0012 affected38 at risk
EG0020 affected39 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Pruritus generalised
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0002 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0004 affected37 at risk
EG0012 affected38 at risk
EG0023 affected39 at risk
EG003
Rash macular
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0022 affected39 at risk
EG003
Rash papular
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0010 affected38 at risk
EG0022 affected39 at risk
EG003
Rash pruritic
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected37 at risk
EG0010 affected38 at risk
EG0021 affected39 at risk
EG003
Skin lesion
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
Hypertension
Vascular disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0013 affected38 at risk
EG0023 affected39 at risk
EG003
Vasculitis
Vascular disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected37 at risk
EG0010 affected38 at risk
EG0020 affected39 at risk
EG003
An unplanned review of unblinded clinical trial data was performed in this study that was not prospectively specified in the protocol. There was no impact on the overall integrity or conclusions of the study.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:
The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
The study has been completed at all study sites for at least 2 years
P-values were obtained from CMH test stratified by randomization stratification factors.
Difference in Response Rates
16.6
2-Sided
95
-5.1
38.3
For the analysis of the difference in response rates, the data with missing response values were imputed by multiple imputation method with logistic regression.
Superiority
OG002
OG003
Cochran-Mantel-Haenszel
0.3309
P-values were obtained from CMH test stratified by randomization stratification factors.
Difference in Response Rates
8.1
2-Sided
95
-13.2
29.4
For the analysis of the difference in response rates, the data with missing response values were imputed by multiple imputation method with logistic regression.
Superiority
Tirabrutinib
Tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet) orally once daily for 48 weeks
OG003
Placebo
Participants received filgotinib placebo + lanraplenib placebo + tirabrutinib placebo tablets orally once daily for 24 weeks. At Week 24 Visit, participants were rerandomized 1:1:1, in a blinded fashion and received either of the three experimental study drugs orally once daily through Week 48:
filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet)
lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet)
tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet)
Units
Counts
Participants
OG00037
OG00138
OG00239
OG00336
Title
Denominators
Categories
Title
Measurements
OG000-2.5± 0.76
OG001-4.7± 0.72
OG002-3.2± 0.73
OG003-3.9± 0.76
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Least Squares (LS) Means, 95% confidence interval (CI), and P-values were obtained from Mixed Effects Model for Repeated Measures (MMRM) with the terms for baseline value, treatment, stratification factors, visit, and treatment-by-visit interaction.
MMRM
0.2066
LS Mean Difference
1.3
Standard Error of the Mean
1.05
2-Sided
95
-0.7
3.4
Superiority
OG001
OG003
LS Means, 95% CI, and P-values were obtained from MMRM with the terms for baseline value, treatment, stratification factors, visit, and treatment-by-visit interaction.
MMRM
0.3998
LS Mean Difference
-0.9
Standard Error of the Mean
1.04
2-Sided
95
-2.9
1.2
Superiority
OG002
OG003
LS Means, 95% CI, and P-values were obtained from MMRM with the terms for baseline value, treatment, stratification factors, visit, and treatment-by-visit interaction.
MMRM
0.5113
LS Mean Difference
0.7
Standard Error of the Mean
1.04
2-Sided
95
-1.4
2.7
Superiority
OG003
Placebo
Participants received filgotinib placebo + lanraplenib placebo + tirabrutinib placebo tablets orally once daily for 24 weeks. At Week 24 Visit, participants were rerandomized 1:1:1, in a blinded fashion and received either of the three experimental study drugs orally once daily through Week 48:
filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet)
lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet)
tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet)
Units
Counts
Participants
OG00037
OG00138
OG00239
OG00336
Title
Denominators
Categories
Title
Measurements
OG000-1.0± 0.34
OG001-1.4± 0.33
OG002-1.4± 0.33
OG003-1.0± 0.34
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
LS Means, 95% CI, and P-values were obtained from MMRM with the terms for baseline value, treatment, stratification factors, visit, and treatment-by-visit interaction.
MMRM
0.9446
LS Mean Difference
0.0
Standard Error of the Mean
0.47
2-Sided
95
-0.9
1.0
Superiority
OG001
OG003
LS Means, 95% CI, and P-values were obtained from MMRM with the terms for baseline value, treatment, stratification factors, visit, and treatment-by-visit interaction.
MMRM
0.3977
LS Mean Difference
-0.4
Standard Error of the Mean
0.47
2-Sided
95
-1.3
0.5
Superiority
OG002
OG003
LS Means, 95% CI, and P-values were obtained from MMRM with the terms for baseline value, treatment, stratification factors, visit, and treatment-by-visit interaction.
MMRM
0.4966
LS Mean Difference
-0.3
Standard Error of the Mean
0.47
2-Sided
95
-1.2
0.6
Superiority
Tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet) orally once daily for 48 weeks
OG003
Placebo
Participants received filgotinib placebo + lanraplenib placebo + tirabrutinib placebo tablets orally once daily for 24 weeks. At Week 24 Visit, participants were rerandomized 1:1:1, in a blinded fashion and received either of the three experimental study drugs orally once daily through Week 48:
filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet)
lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet)
tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet)
Units
Counts
Participants
OG00037
OG00138
OG00239
OG00336
Title
Denominators
Categories
Title
Measurements
OG000-4.3± 0.81
OG001-5.4± 0.75
OG002-4.0± 0.75
OG003-4.2± 0.78
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
LS Means, 95% CI, and P-values were obtained from MMRM with the terms for baseline value, treatment, stratification factors, visit, and treatment-by-visit interaction.
MMRM
0.9564
LS Mean Difference
-0.1
Standard Error of the Mean
1.10
2-Sided
95
-2.2
2.1
Superiority
OG001
OG003
LS Means, 95% CI, and P-values were obtained from MMRM with the terms for baseline value, treatment, stratification factors, visit, and treatment-by-visit interaction.
MMRM
0.2788
LS Mean Difference
-1.2
Standard Error of the Mean
1.07
2-Sided
95
-3.3
0.9
Superiority
OG002
OG003
LS Means, 95% CI, and P-values were obtained from MMRM with the terms for baseline value, treatment, stratification factors, visit, and treatment-by-visit interaction.
MMRM
0.8047
LS Mean Difference
0.3
Standard Error of the Mean
1.06
2-Sided
95
-1.8
2.3
Superiority
OG003
Placebo
Participants received filgotinib placebo + lanraplenib placebo + tirabrutinib placebo tablets orally once daily for 24 weeks. At Week 24 Visit, participants were rerandomized 1:1:1, in a blinded fashion and received either of the three experimental study drugs orally once daily through Week 48:
filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet)
lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet)
tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet)
Units
Counts
Participants
OG00037
OG00138
OG00239
OG00336
Title
Denominators
Categories
Title
Measurements
OG000-1.1± 0.34
OG001-0.8± 0.31
OG002-1.2± 0.31
OG003-0.9± 0.33
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
LS Means, 95% CI, and P-values were obtained from MMRM with the terms for baseline value, treatment, stratification factors, visit, and treatment-by-visit interaction.
MMRM
0.6782
LS Mean Difference
-0.2
Standard Error of the Mean
0.46
2-Sided
95
-1.1
0.7
Superiority
OG001
OG003
LS Means, 95% CI, and P-values were obtained from MMRM with the terms for baseline value, treatment, stratification factors, visit, and treatment-by-visit interaction.
MMRM
0.9171
LS Mean Difference
0.0
Standard Error of the Mean
0.45
2-Sided
95
-0.8
0.9
Superiority
OG002
OG003
LS Means, 95% CI, and P-values were obtained from MMRM with the terms for baseline value, treatment, stratification factors, visit, and treatment-by-visit interaction.