Clincosm LogoSign in Get a demo

Study to Assess Safety and Efficacy of Filgotinib, Lanraplenib and Tirabrutinib in Adults With Active Sjogren's Syndrome

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT03100942
Collaborator
Galapagos NV (Industry), Ono Pharmaceutical Co. Ltd (Industry)
152
Enrollment
53
Locations
4
Arms
29
Actual Duration (Months)
2.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
152 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
May 1, 2017
Actual Primary Completion Date :
Jan 10, 2019
Actual Study Completion Date :
Oct 2, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Lanraplenib

Lanraplenib + filgotinib placebo + tirabrutinib placebo for up to 49.4 weeks.

Drug: Lanraplenib
1 x 30 mg tablet administered orally once daily
Other Names:
  • GS-9876

    • Drug: Filgotinib placebo
    1 x tablet administered orally once daily

    Drug: Tirabrutinib placebo
    1 x tablet administered orally once daily
    Experimental: Filgotinib

    Filgotinib + lanraplenib placebo + tirabrutinib placebo for up to 50.4 weeks.

    Drug: Filgotinib
    1 x 200 mg tablet administered orally once daily
    Other Names:
  • GS-6034

    • Drug: Lanraplenib placebo
    1 x tablet administered orally once daily

    Drug: Tirabrutinib placebo
    1 x tablet administered orally once daily
    Experimental: Tirabrutinib

    Tirabrutinib + filgotinib placebo + lanraplenib placebo for up to 50.3 weeks.

    Drug: Tirabrutinib
    1 x 40 mg tablet administered orally once daily
    Other Names:
  • GS-4059

    • Drug: Lanraplenib placebo
    1 x tablet administered orally once daily

    Drug: Filgotinib placebo
    1 x tablet administered orally once daily
    Placebo Comparator: Placebo, then active treatment

    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: filgotinib + lanraplenib placebo + tirabrutinib placebo lanraplenib + filgotinib placebo + tirabrutinib placebo tirabrutinib + filgotinib placebo + lanraplenib placebo

    Drug: Lanraplenib
    1 x 30 mg tablet administered orally once daily
    Other Names:
  • GS-9876

    • Drug: Filgotinib
    1 x 200 mg tablet administered orally once daily
    Other Names:
  • GS-6034

    • Drug: Tirabrutinib
    1 x 40 mg tablet administered orally once daily
    Other Names:
  • GS-4059

    • Drug: Lanraplenib placebo
    1 x tablet administered orally once daily

    Drug: Filgotinib placebo
    1 x tablet administered orally once daily

    Drug: Tirabrutinib placebo
    1 x tablet administered orally once daily

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Fulfilling Protocol-Specified Response Criteria at Week 12, as Compared to Baseline [Week 12]

      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).

    Secondary Outcome Measures

    1. Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) at Week 12 [Baseline; 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.

    2. Change From Baseline in EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) at Week 12 [Baseline; 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.

    3. Change From Baseline in ESSDAI at Week 24 [Baseline; 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.

    4. Change From Baseline in ESSPRI at Week 24 [Baseline; 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 AARR Arizona Arthritis & Rheumatology Research Mesa Arizona United States 85202
    2 AARR Arizona Arthritis & Rheumatology Research Phoenix Arizona United States 85032
    3 Medvin Clinical Research Covina California United States 91723
    4 Inland Rheumatology Clinical Trials, Inc. Upland California United States 91786
    5 Denver Arthritis Clinic Denver Colorado United States 80230
    6 Clinical Research of West Florida, Inc. Clearwater Florida United States 33765
    7 Omega Research Consultants LLC DeBary Florida United States 32713
    8 Center for Rheumatology Immunology and Arthritis Fort Lauderdale Florida United States 33309
    9 Suncoast Clinical Research, Inc. New Port Richey Florida United States 34668
    10 IRIS Research and Development, LLC Plantation Florida United States 33324
    11 North Georgia Rheumatology Group, PC Lawrenceville Georgia United States 30046
    12 Springfield Clinic Springfield Illinois United States 62703
    13 Center for Arthritis & Osteoporosis Elizabethtown Kentucky United States 42701
    14 June DO, PC Lansing Michigan United States 48910
    15 North Mississippi Medical Clinics, Inc. - Clinical Research Tupelo Mississippi United States 38801
    16 Clayton Medical Associates Saint Louis Missouri United States 63117
    17 Physician Research Collaboration, LLC Lincoln Nebraska United States 68516
    18 Albuquerque Clinical Trials Albuquerque New Mexico United States 87102
    19 Joint and Muscle Research Institute Charlotte North Carolina United States 28204
    20 Cape Fear Arthritis Care, PLLC Leland North Carolina United States 28451
    21 PMG Research of Salisbury Salisbury North Carolina United States 28144
    22 East Penn Rheumatology Associates, P.C. Bethlehem Pennsylvania United States 18015
    23 Altoona Center for Clinical Research Duncansville Pennsylvania United States 16635
    24 Clinical Research Center of Reading, LLC Wyomissing Pennsylvania United States 19610
    25 ClinSearch Chattanooga Tennessee United States 37421
    26 Ramesh C. Gupta, MD Memphis Tennessee United States 38119
    27 Diagnostic Group Integrated Healthcare System, Pllc Beaumont Texas United States 77701
    28 Accurate Clinical Research Inc. Houston Texas United States 77034
    29 Southwest Rheumatology Research Mesquite Texas United States 75150
    30 Trinity Universal Research Associates Plano Texas United States 75024
    31 Arthritis & Osteoporosis Clinic Waco Texas United States 76710
    32 Wasatch Peak Family Practice Layton Utah United States 84041
    33 The Center for Arthritis and Rheumatic Diseases, PC Chesapeake Virginia United States 23320
    34 Arthritis Northwest Spokane Washington United States 99204
    35 Centrum Kliniczno-Badawcze Elbląg Poland 82-300
    36 Intermedius Kościan Poland 64-000
    37 Centrum Badan Klinicznych S.C Poznan Poland 60-733
    38 Ai Centrum Medyczne Poznan Poland 61-113
    39 Centrum Medyczne Amed Warszawa Targowek Warszawa Poland 03-921
    40 Centrum Medyczne Oporow Wroclaw Poland 52-416
    41 Hospital de la Santa Creu i Sant Pau Barcelona Spain 08025
    42 Hospital General Universitario De Elche Elche Spain 03203
    43 Hospital Universitario de Fuenlabrada Fuenlabrada Spain 28942
    44 Hospital Regional Universitario de Malaga Málaga Spain 29009
    45 Hospital De Merida Mérida Spain 6800
    46 Corporacio Sanitaria Parc Taulí de Sabadell Sabadell Spain 08208
    47 Hospital Clinico Universitario de Salamanca San Vicente Spain 37007
    48 Hospital Quironsalud Infanta Luisa Sevilla Spain 41010
    49 Doncaster Royal Infirmary Doncaster United Kingdom DN2 5LT
    50 Western General Hospital Edinburgh United Kingdom EX4 2XU
    51 Princess Alexandra Hospital Harlow United Kingdom CM20 1QX
    52 Great Western Hospital Swindon United Kingdom SN3 6BB
    53 Warrington Hospital Warrington United Kingdom WA5 1QG

    Sponsors and Collaborators

    • Gilead Sciences
    • Galapagos NV
    • Ono Pharmaceutical Co. Ltd

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT03100942
    Other Study ID Numbers:
    • GS-US-445-4189
    • 2016-003558-34
    First Posted:
    Apr 4, 2017
    Last Update Posted:
    Oct 23, 2020
    Last Verified:
    Oct 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Sjogren's Syndrome
    Syndrome

    Study Results

    Participant Flow

    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.
    Pre-assignment Detail 348 participants were screened.
    Arm/Group Title Lanraplenib Filgotinib Tirabrutinib Placebo Placebo to Lanraplenib Placebo to Filgotinib Placebo to Tirabrutinib
    Arm/Group Description 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. 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 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 Participants received filgotinib placebo + lanraplenib placebo + tirabrutinib placebo tablets orally once daily for 24 weeks. 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: filgotinib + lanraplenib placebo + tirabrutinib placebo lanraplenib + filgotinib placebo + tirabrutinib placebo tirabrutinib + filgotinib placebo + lanraplenib placebo 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. 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. 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.
    Period Title: Randomized Treatment Period
    STARTED 38 38 39 37 0 0 0
    COMPLETED 26 29 33 32 0 0 0
    NOT COMPLETED 12 9 6 5 0 0 0
    Period Title: Randomized Treatment Period
    STARTED 0 0 0 0 10 12 10
    COMPLETED 0 0 0 0 10 12 9
    NOT COMPLETED 0 0 0 0 0 0 1

    Baseline Characteristics

    Arm/Group Title Lanraplenib Filgotinib Tirabrutinib Placebo Total
    Arm/Group Description 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. 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. 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. 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) Total of all reporting groups
    Overall Participants 37 38 39 36 150
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    56.2
    (9.72)
    52.2
    (10.54)
    55.8
    (10.06)
    53.2
    (10.28)
    54.4
    (10.20)
    Sex: Female, Male (Count of Participants)
    Female
    36
    97.3%
    38
    100%
    37
    94.9%
    35
    97.2%
    146
    97.3%
    Male
    1
    2.7%
    0
    0%
    2
    5.1%
    1
    2.8%
    4
    2.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    6
    16.2%
    4
    10.5%
    1
    2.6%
    6
    16.7%
    17
    11.3%
    Not Hispanic or Latino
    31
    83.8%
    34
    89.5%
    38
    97.4%
    30
    83.3%
    133
    88.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    1
    2.8%
    1
    0.7%
    Asian
    0
    0%
    1
    2.6%
    1
    2.6%
    0
    0%
    2
    1.3%
    Black
    5
    13.5%
    5
    13.2%
    4
    10.3%
    5
    13.9%
    19
    12.7%
    White
    31
    83.8%
    32
    84.2%
    34
    87.2%
    30
    83.3%
    127
    84.7%
    Other
    1
    2.7%
    0
    0%
    0
    0%
    0
    0%
    1
    0.7%
    Region of Enrollment (participants) [Number]
    United States
    26
    70.3%
    27
    71.1%
    30
    76.9%
    23
    63.9%
    106
    70.7%
    Poland
    7
    18.9%
    4
    10.5%
    5
    12.8%
    6
    16.7%
    22
    14.7%
    Spain
    2
    5.4%
    4
    10.5%
    3
    7.7%
    4
    11.1%
    13
    8.7%
    United Kingdom
    2
    5.4%
    3
    7.9%
    1
    2.6%
    3
    8.3%
    9
    6%
    European League Against Rheumatism (EULAR) Sjogren's syndrome disease activity index (ESSDAI) (Score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Score on a scale]
    10.5
    (4.89)
    10.2
    (6.23)
    10.4
    (5.36)
    9.3
    (3.96)
    10.1
    (5.16)
    EULAR Sjogren's syndrome patient reported index (ESSPRI) (Score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Score on a scale]
    6.6
    (1.90)
    6.3
    (2.31)
    5.9
    (2.39)
    5.9
    (2.24)
    6.2
    (2.22)

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Fulfilling Protocol-Specified Response Criteria at Week 12, as Compared to Baseline
    Description 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).
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set included all randomized participants who received at least one dose of study drug. Included participants with available data.
    Arm/Group Title Lanraplenib Filgotinib Tirabrutinib Placebo
    Arm/Group Description Lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks Filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks Tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet) orally once daily for 48 weeks 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)
    Measure Participants 35 37 37 34
    Number (95% Confidence Interval) [percentage of participants]
    42.9
    115.9%
    43.2
    113.7%
    35.1
    90%
    26.5
    73.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lanraplenib, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1597
    Comments P-values were obtained from Cochran-Mantel-Haenszel (CMH) test stratified by randomization stratification factors.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in Response Rates
    Estimated Value 15.6
    Confidence Interval (2-Sided) 95%
    -6.3 to 37.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments For the analysis of the difference in response rates, the data with missing response values were imputed by multiple imputation method with logistic regression.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1694
    Comments P-values were obtained from CMH test stratified by randomization stratification factors.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in Response Rates
    Estimated Value 16.6
    Confidence Interval (2-Sided) 95%
    -5.1 to 38.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments For the analysis of the difference in response rates, the data with missing response values were imputed by multiple imputation method with logistic regression.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tirabrutinib, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3309
    Comments P-values were obtained from CMH test stratified by randomization stratification factors.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in Response Rates
    Estimated Value 8.1
    Confidence Interval (2-Sided) 95%
    -13.2 to 29.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments For the analysis of the difference in response rates, the data with missing response values were imputed by multiple imputation method with logistic regression.
    2. Secondary Outcome
    Title Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) at Week 12
    Description 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.
    Time Frame Baseline; Week 12

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title Lanraplenib Filgotinib Tirabrutinib Placebo
    Arm/Group Description Lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks Filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks Tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet) orally once daily for 48 weeks 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)
    Measure Participants 37 38 39 36
    Least Squares Mean (Standard Error) [score on a scale]
    -2.5
    (0.76)
    -4.7
    (0.72)
    -3.2
    (0.73)
    -3.9
    (0.76)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lanraplenib, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2066
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 1.3
    Confidence Interval (2-Sided) 95%
    -0.7 to 3.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.05
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3998
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -2.9 to 1.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.04
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tirabrutinib, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5113
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.7
    Confidence Interval (2-Sided) 95%
    -1.4 to 2.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.04
    Estimation Comments
    3. Secondary Outcome
    Title Change From Baseline in EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) at Week 12
    Description 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.
    Time Frame Baseline; Week 12

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title Lanraplenib Filgotinib Tirabrutinib Placebo
    Arm/Group Description Lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks Filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks Tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet) orally once daily for 48 weeks 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)
    Measure Participants 37 38 39 36
    Least Squares Mean (Standard Error) [score on a scale]
    -1.0
    (0.34)
    -1.4
    (0.33)
    -1.4
    (0.33)
    -1.0
    (0.34)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lanraplenib, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9446
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.9 to 1.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.47
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3977
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -1.3 to 0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.47
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tirabrutinib, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4966
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -1.2 to 0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.47
    Estimation Comments
    4. Secondary Outcome
    Title Change From Baseline in ESSDAI at Week 24
    Description 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.
    Time Frame Baseline; Week 24

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title Lanraplenib Filgotinib Tirabrutinib Placebo
    Arm/Group Description Lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks Filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks Tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet) orally once daily for 48 weeks 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)
    Measure Participants 37 38 39 36
    Least Squares Mean (Standard Error) [score on a scale]
    -4.3
    (0.81)
    -5.4
    (0.75)
    -4.0
    (0.75)
    -4.2
    (0.78)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lanraplenib, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9564
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -2.2 to 2.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.10
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2788
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -3.3 to 0.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.07
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tirabrutinib, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8047
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -1.8 to 2.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.06
    Estimation Comments
    5. Secondary Outcome
    Title Change From Baseline in ESSPRI at Week 24
    Description 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.
    Time Frame Baseline; Week 24

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title Lanraplenib Filgotinib Tirabrutinib Placebo
    Arm/Group Description Lanraplenib (1 x 30 mg tablet) + filgotinib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks Filgotinib (1 x 200 mg tablet) + lanraplenib placebo (1 x tablet) + tirabrutinib placebo (1 x tablet) orally once daily for 48 weeks Tirabrutinib (1 x 40 mg tablet) + filgotinib placebo (1 x tablet) + lanraplenib placebo (1 x tablet) orally once daily for 48 weeks 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)
    Measure Participants 37 38 39 36
    Least Squares Mean (Standard Error) [score on a scale]
    -1.1
    (0.34)
    -0.8
    (0.31)
    -1.2
    (0.31)
    -0.9
    (0.33)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lanraplenib, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6782
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -1.1 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.46
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9171
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.8 to 0.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.45
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tirabrutinib, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4641
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -1.2 to 0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.45
    Estimation Comments

    Adverse Events

    Time Frame First dose date up to last dose date (Maximum: 50.4 weeks) plus 30 days
    Adverse Event Reporting Description The Safety Analysis Set included participants who received at least one dose of study drug.
    Arm/Group Title Lanraplenib Filgotinib Tirabrutinib Placebo to Lanraplenib Placebo to Filgotinib Placebo to Tirabrutinib Placebo on Placebo Controlled Period
    Arm/Group Description 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. 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. 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. 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. 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. 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. 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: filgotinib + lanraplenib placebo + tirabrutinib placebo lanraplenib + filgotinib placebo + tirabrutinib placebo tirabrutinib + filgotinib placebo + lanraplenib placeboy once daily for 24 weeks.
    All Cause Mortality
    Lanraplenib Filgotinib Tirabrutinib Placebo to Lanraplenib Placebo to Filgotinib Placebo to Tirabrutinib Placebo on Placebo Controlled Period
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Serious Adverse Events
    Lanraplenib Filgotinib Tirabrutinib Placebo to Lanraplenib Placebo to Filgotinib Placebo to Tirabrutinib Placebo on Placebo Controlled Period
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/37 (8.1%) 5/38 (13.2%) 1/39 (2.6%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 2/36 (5.6%)
    Cardiac disorders
    Acute coronary syndrome 1/37 (2.7%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Gastrointestinal disorders
    Gastrooesophageal reflux disease 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 1/36 (2.8%)
    Pancreatitis 0/37 (0%) 1/38 (2.6%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Pancreatitis acute 1/37 (2.7%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Infections and infestations
    Diverticulitis 0/37 (0%) 1/38 (2.6%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/37 (0%) 0/38 (0%) 1/39 (2.6%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Rheumatoid arthritis 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 1/36 (2.8%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Nervous system disorders
    Migraine 0/37 (0%) 1/38 (2.6%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Psychiatric disorders
    Suicidal ideation 1/37 (2.7%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Renal and urinary disorders
    Renal failure 0/37 (0%) 1/38 (2.6%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Respiratory, thoracic and mediastinal disorders
    Interstitial lung disease 0/37 (0%) 1/38 (2.6%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Other (Not Including Serious) Adverse Events
    Lanraplenib Filgotinib Tirabrutinib Placebo to Lanraplenib Placebo to Filgotinib Placebo to Tirabrutinib Placebo on Placebo Controlled Period
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 30/37 (81.1%) 31/38 (81.6%) 32/39 (82.1%) 10/10 (100%) 10/12 (83.3%) 7/10 (70%) 23/36 (63.9%)
    Blood and lymphatic system disorders
    Anaemia 1/37 (2.7%) 0/38 (0%) 2/39 (5.1%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Lymphadenopathy 2/37 (5.4%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 0/36 (0%)
    Lymphopenia 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Neutropenia 2/37 (5.4%) 2/38 (5.3%) 0/39 (0%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Eye disorders
    Corneal erosion 0/37 (0%) 0/38 (0%) 0/39 (0%) 1/10 (10%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Vision blurred 0/37 (0%) 1/38 (2.6%) 1/39 (2.6%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Gastrointestinal disorders
    Abdominal pain upper 0/37 (0%) 1/38 (2.6%) 1/39 (2.6%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 0/36 (0%)
    Constipation 0/37 (0%) 0/38 (0%) 3/39 (7.7%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Dental caries 2/37 (5.4%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Diarrhoea 3/37 (8.1%) 3/38 (7.9%) 3/39 (7.7%) 1/10 (10%) 2/12 (16.7%) 0/10 (0%) 1/36 (2.8%)
    Food poisoning 0/37 (0%) 1/38 (2.6%) 0/39 (0%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Gastrooesophageal reflux disease 0/37 (0%) 0/38 (0%) 1/39 (2.6%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 1/36 (2.8%)
    Lip blister 0/37 (0%) 2/38 (5.3%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Nausea 2/37 (5.4%) 4/38 (10.5%) 2/39 (5.1%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 1/36 (2.8%)
    Vomiting 2/37 (5.4%) 3/38 (7.9%) 2/39 (5.1%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    General disorders
    Asthenia 0/37 (0%) 1/38 (2.6%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 0/36 (0%)
    Fatigue 4/37 (10.8%) 0/38 (0%) 3/39 (7.7%) 2/10 (20%) 1/12 (8.3%) 0/10 (0%) 2/36 (5.6%)
    Pyrexia 3/37 (8.1%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 1/36 (2.8%)
    Immune system disorders
    Seasonal allergy 1/37 (2.7%) 1/38 (2.6%) 2/39 (5.1%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Infections and infestations
    Bronchitis 2/37 (5.4%) 3/38 (7.9%) 1/39 (2.6%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 3/36 (8.3%)
    Conjunctivitis viral 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Fungal skin infection 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Furuncle 1/37 (2.7%) 0/38 (0%) 1/39 (2.6%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Gastroenteritis viral 3/37 (8.1%) 2/38 (5.3%) 3/39 (7.7%) 2/10 (20%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Helicobacter infection 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 1/36 (2.8%)
    Herpes zoster 0/37 (0%) 2/38 (5.3%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Influenza 1/37 (2.7%) 0/38 (0%) 3/39 (7.7%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Laryngitis 2/37 (5.4%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Lower respiratory tract infection 2/37 (5.4%) 0/38 (0%) 1/39 (2.6%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Nasopharyngitis 3/37 (8.1%) 6/38 (15.8%) 4/39 (10.3%) 1/10 (10%) 1/12 (8.3%) 2/10 (20%) 4/36 (11.1%)
    Oral herpes 2/37 (5.4%) 3/38 (7.9%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Otitis media 0/37 (0%) 1/38 (2.6%) 0/39 (0%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Pharyngitis 0/37 (0%) 2/38 (5.3%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 2/36 (5.6%)
    Pneumonia 0/37 (0%) 2/38 (5.3%) 1/39 (2.6%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Sinusitis 2/37 (5.4%) 1/38 (2.6%) 5/39 (12.8%) 1/10 (10%) 0/12 (0%) 0/10 (0%) 3/36 (8.3%)
    Upper respiratory tract infection 4/37 (10.8%) 6/38 (15.8%) 9/39 (23.1%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 4/36 (11.1%)
    Urinary tract infection 1/37 (2.7%) 2/38 (5.3%) 4/39 (10.3%) 2/10 (20%) 2/12 (16.7%) 0/10 (0%) 6/36 (16.7%)
    Vaginal infection 0/37 (0%) 0/38 (0%) 0/39 (0%) 1/10 (10%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Viral pharyngitis 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 0/36 (0%)
    Vulvovaginal mycotic infection 0/37 (0%) 0/38 (0%) 2/39 (5.1%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Injury, poisoning and procedural complications
    Arthropod bite 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 0/36 (0%)
    Contusion 0/37 (0%) 2/38 (5.3%) 2/39 (5.1%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 1/36 (2.8%)
    Fall 1/37 (2.7%) 2/38 (5.3%) 2/39 (5.1%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Investigations
    Alanine aminotransferase increased 4/37 (10.8%) 1/38 (2.6%) 2/39 (5.1%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Aspartate aminotransferase increased 4/37 (10.8%) 1/38 (2.6%) 1/39 (2.6%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Blood creatine phosphokinase increased 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Blood potassium increased 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Light chain analysis increased 0/37 (0%) 0/38 (0%) 1/39 (2.6%) 1/10 (10%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Liver function test abnormal 0/37 (0%) 0/38 (0%) 0/39 (0%) 1/10 (10%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Transaminases increased 0/37 (0%) 0/38 (0%) 0/39 (0%) 1/10 (10%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 4/37 (10.8%) 4/38 (10.5%) 6/39 (15.4%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Back pain 1/37 (2.7%) 1/38 (2.6%) 1/39 (2.6%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 0/36 (0%)
    Exostosis 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 0/36 (0%)
    Muscle spasms 0/37 (0%) 2/38 (5.3%) 2/39 (5.1%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Musculoskeletal pain 1/37 (2.7%) 1/38 (2.6%) 0/39 (0%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Myalgia 2/37 (5.4%) 0/38 (0%) 1/39 (2.6%) 1/10 (10%) 0/12 (0%) 1/10 (10%) 1/36 (2.8%)
    Neck pain 0/37 (0%) 1/38 (2.6%) 1/39 (2.6%) 2/10 (20%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Osteoarthritis 1/37 (2.7%) 2/38 (5.3%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 1/36 (2.8%)
    Pain in extremity 0/37 (0%) 3/38 (7.9%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Rheumatoid arthritis 1/37 (2.7%) 1/38 (2.6%) 0/39 (0%) 1/10 (10%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Temporomandibular joint syndrome 0/37 (0%) 1/38 (2.6%) 0/39 (0%) 2/10 (20%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Nervous system disorders
    Dizziness 3/37 (8.1%) 1/38 (2.6%) 1/39 (2.6%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 3/36 (8.3%)
    Headache 0/37 (0%) 3/38 (7.9%) 3/39 (7.7%) 1/10 (10%) 1/12 (8.3%) 1/10 (10%) 1/36 (2.8%)
    Migraine 1/37 (2.7%) 1/38 (2.6%) 0/39 (0%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Sciatica 0/37 (0%) 3/38 (7.9%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Psychiatric disorders
    Insomnia 1/37 (2.7%) 1/38 (2.6%) 2/39 (5.1%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 1/36 (2.8%)
    Respiratory, thoracic and mediastinal disorders
    Allergic sinusitis 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Cough 0/37 (0%) 1/38 (2.6%) 3/39 (7.7%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 3/36 (8.3%)
    Epistaxis 0/37 (0%) 0/38 (0%) 1/39 (2.6%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 0/36 (0%)
    Oropharyngeal pain 0/37 (0%) 2/38 (5.3%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 0/36 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 0/37 (0%) 2/38 (5.3%) 2/39 (5.1%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 2/36 (5.6%)
    Hyperhidrosis 1/37 (2.7%) 2/38 (5.3%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Pruritus 0/37 (0%) 0/38 (0%) 0/39 (0%) 1/10 (10%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Pruritus generalised 2/37 (5.4%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Rash 4/37 (10.8%) 2/38 (5.3%) 3/39 (7.7%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 2/36 (5.6%)
    Rash macular 0/37 (0%) 0/38 (0%) 2/39 (5.1%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Rash papular 1/37 (2.7%) 0/38 (0%) 2/39 (5.1%) 0/10 (0%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Rash pruritic 1/37 (2.7%) 0/38 (0%) 1/39 (2.6%) 1/10 (10%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Skin lesion 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 0/36 (0%)
    Urticaria 0/37 (0%) 0/38 (0%) 0/39 (0%) 1/10 (10%) 0/12 (0%) 0/10 (0%) 0/36 (0%)
    Vascular disorders
    Hypertension 0/37 (0%) 3/38 (7.9%) 3/39 (7.7%) 0/10 (0%) 1/12 (8.3%) 0/10 (0%) 0/36 (0%)
    Vasculitis 0/37 (0%) 0/38 (0%) 0/39 (0%) 0/10 (0%) 0/12 (0%) 1/10 (10%) 0/36 (0%)

    Limitations/Caveats

    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.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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

    Results Point of Contact

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT03100942
    Other Study ID Numbers:
    • GS-US-445-4189
    • 2016-003558-34
    First Posted:
    Apr 4, 2017
    Last Update Posted:
    Oct 23, 2020
    Last Verified:
    Oct 1, 2020