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

Study Overview
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Brief Summary
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The primary objective of this study is to assess the efficacy of filgotinib, lanraplenib, and tirabrutinib in adults with active Sjogren's Syndrome (SjS).

Official Title
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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

Conditions
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Sjogren's Syndrome

Intervention / Treatment
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* Drug: Lanraplenib
* Drug: Filgotinib
* Drug: Tirabrutinib
* Drug: Lanraplenib placebo
* Drug: Filgotinib placebo
* Drug: Tirabrutinib placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lanraplenib<br>Lanraplenib + filgotinib placebo + tirabrutinib placebo for up to 49.4 weeks. | Drug: Lanraplenib<br>* 1 x 30 mg tablet administered orally once daily<br>* Other names: GS-9876;Drug: Filgotinib placebo<br>* 1 x tablet administered orally once daily<br>Drug: Tirabrutinib placebo<br>* 1 x tablet administered orally once daily<br>|
| Experimental: Filgotinib<br>Filgotinib + lanraplenib placebo + tirabrutinib placebo for up to 50.4 weeks. | Drug: Filgotinib<br>* 1 x 200 mg tablet administered orally once daily<br>* Other names: GS-6034;Drug: Lanraplenib placebo<br>* 1 x tablet administered orally once daily<br>Drug: Tirabrutinib placebo<br>* 1 x tablet administered orally once daily<br>|
| Experimental: Tirabrutinib<br>Tirabrutinib + filgotinib placebo + lanraplenib placebo for up to 50.3 weeks. | Drug: Tirabrutinib<br>* 1 x 40 mg tablet administered orally once daily<br>* Other names: GS-4059;Drug: Lanraplenib placebo<br>* 1 x tablet administered orally once daily<br>Drug: Filgotinib placebo<br>* 1 x tablet administered orally once daily<br>|
| Placebo Comparator: Placebo, then active treatment<br>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<br>* 1 x 30 mg tablet administered orally once daily<br>* Other names: GS-9876;Drug: Filgotinib<br>* 1 x 200 mg tablet administered orally once daily<br>* Other names: GS-6034;Drug: Tirabrutinib<br>* 1 x 40 mg tablet administered orally once daily<br>* Other names: GS-4059;Drug: Lanraplenib placebo<br>* 1 x tablet administered orally once daily<br>Drug: Filgotinib placebo<br>* 1 x tablet administered orally once daily<br>Drug: Tirabrutinib placebo<br>* 1 x tablet administered orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | 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. | 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 |