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

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

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

Study Overview

• Status: Completed
• Conditions: Sjogren's Syndrome
• Intervention / Treatment: Drug: Lanraplenib; Drug: Filgotinib placebo; Drug: Tirabrutinib placebo; Drug: Filgotinib; Drug: Lanraplenib placebo; Drug: Tirabrutinib

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / 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: Tirabrutinib placebo; 1 x tablet administered orally once daily; 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
Experimental: Tirabrutinib; Tirabrutinib + filgotinib placebo + lanraplenib placebo for up to 50.3 weeks.	Drug: Filgotinib placebo; 1 x tablet administered orally once daily; Drug: Lanraplenib placebo; 1 x tablet administered orally once daily; Drug: Tirabrutinib; 1 x 40 mg tablet administered orally once daily; Other Names: GS-4059
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 placebo; 1 x tablet administered orally once daily; Drug: Tirabrutinib placebo; 1 x tablet administered orally once daily; 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; 1 x 40 mg tablet administered orally once daily; Other Names: GS-4059

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: Ono Pharmaceutical Co. Ltd; Galapagos NV

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): January 10, 2019
• Study Completion (Actual): October 2, 2019

Study Registration Dates

• First Submitted: March 31, 2017
• First Submitted That Met QC Criteria: March 31, 2017
• First Posted (Actual): April 4, 2017

Study Record Updates

• Last Update Posted (Actual): October 23, 2020
• Last Update Submitted That Met QC Criteria: October 1, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Sjogren's Syndrome
• Other Study ID Numbers: GS-US-445-4189; 2016-003558-34 (EudraCT Number)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No