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

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ClinicalTrials.gov Identifier: NCT03100942
Recruitment Status : Completed
First Posted : April 4, 2017
Results First Posted : January 22, 2020
Last Update Posted : October 23, 2020
Sponsor:
Collaborators:
Galapagos NV
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Gilead Sciences

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
Sjogren's Syndrome Drug: Lanraplenib Drug: Filgotinib Drug: Tirabrutinib Drug: Lanraplenib placebo Drug: Filgotinib placebo Drug: Tirabrutinib placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
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 : January 10, 2019
Actual Study Completion Date : October 2, 2019

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: 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 Name: GS-9876

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

Drug: Tirabrutinib
1 x 40 mg tablet administered orally once daily
Other Name: 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




Primary Outcome Measures :
  1. Percentage of Participants Fulfilling Protocol-Specified Response Criteria at Week 12, as Compared to Baseline [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03100942


Locations
Hide Hide 53 study locations
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United States, Arizona
AARR Arizona Arthritis & Rheumatology Research
Mesa, Arizona, United States, 85202
AARR Arizona Arthritis & Rheumatology Research
Phoenix, Arizona, United States, 85032
United States, California
Medvin Clinical Research
Covina, California, United States, 91723
Inland Rheumatology Clinical Trials, Inc.
Upland, California, United States, 91786
United States, Colorado
Denver Arthritis Clinic
Denver, Colorado, United States, 80230
United States, Florida
Clinical Research of West Florida, Inc.
Clearwater, Florida, United States, 33765
Omega Research Consultants LLC
DeBary, Florida, United States, 32713
Center for Rheumatology Immunology and Arthritis
Fort Lauderdale, Florida, United States, 33309
Suncoast Clinical Research, Inc.
New Port Richey, Florida, United States, 34668
IRIS Research and Development, LLC
Plantation, Florida, United States, 33324
United States, Georgia
North Georgia Rheumatology Group, PC
Lawrenceville, Georgia, United States, 30046
United States, Illinois
Springfield Clinic
Springfield, Illinois, United States, 62703
United States, Kentucky
Center for Arthritis & Osteoporosis
Elizabethtown, Kentucky, United States, 42701
United States, Michigan
June DO, PC
Lansing, Michigan, United States, 48910
United States, Mississippi
North Mississippi Medical Clinics, Inc. - Clinical Research
Tupelo, Mississippi, United States, 38801
United States, Missouri
Clayton Medical Associates
Saint Louis, Missouri, United States, 63117
United States, Nebraska
Physician Research Collaboration, LLC
Lincoln, Nebraska, United States, 68516
United States, New Mexico
Albuquerque Clinical Trials
Albuquerque, New Mexico, United States, 87102
United States, North Carolina
Joint and Muscle Research Institute
Charlotte, North Carolina, United States, 28204
Cape Fear Arthritis Care, PLLC
Leland, North Carolina, United States, 28451
PMG Research of Salisbury
Salisbury, North Carolina, United States, 28144
United States, Pennsylvania
East Penn Rheumatology Associates, P.C.
Bethlehem, Pennsylvania, United States, 18015
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States, 16635
Clinical Research Center of Reading, LLC
Wyomissing, Pennsylvania, United States, 19610
United States, Tennessee
ClinSearch
Chattanooga, Tennessee, United States, 37421
Ramesh C. Gupta, MD
Memphis, Tennessee, United States, 38119
United States, Texas
Diagnostic Group Integrated Healthcare System, Pllc
Beaumont, Texas, United States, 77701
Accurate Clinical Research Inc.
Houston, Texas, United States, 77034
Southwest Rheumatology Research
Mesquite, Texas, United States, 75150
Trinity Universal Research Associates
Plano, Texas, United States, 75024
Arthritis & Osteoporosis Clinic
Waco, Texas, United States, 76710
United States, Utah
Wasatch Peak Family Practice
Layton, Utah, United States, 84041
United States, Virginia
The Center for Arthritis and Rheumatic Diseases, PC
Chesapeake, Virginia, United States, 23320
United States, Washington
Arthritis Northwest
Spokane, Washington, United States, 99204
Poland
Centrum Kliniczno-Badawcze
Elbląg, Poland, 82-300
Intermedius
Kościan, Poland, 64-000
Centrum Badan Klinicznych S.C
Poznan, Poland, 60-733
Ai Centrum Medyczne
Poznan, Poland, 61-113
Centrum Medyczne Amed Warszawa Targowek
Warszawa, Poland, 03-921
Centrum Medyczne Oporow
Wroclaw, Poland, 52-416
Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Hospital General Universitario De Elche
Elche, Spain, 03203
Hospital Universitario de Fuenlabrada
Fuenlabrada, Spain, 28942
Hospital Regional Universitario de Malaga
Málaga, Spain, 29009
Hospital De Merida
Mérida, Spain, 6800
Corporacio Sanitaria Parc Taulí de Sabadell
Sabadell, Spain, 08208
Hospital Clinico Universitario de Salamanca
San Vicente, Spain, 37007
Hospital Quironsalud Infanta Luisa
Sevilla, Spain, 41010
United Kingdom
Doncaster Royal Infirmary
Doncaster, United Kingdom, DN2 5LT
Western General Hospital
Edinburgh, United Kingdom, EX4 2XU
Princess Alexandra Hospital
Harlow, United Kingdom, CM20 1QX
Great Western Hospital
Swindon, United Kingdom, SN3 6BB
Warrington Hospital
Warrington, United Kingdom, WA5 1QG
Sponsors and Collaborators
Gilead Sciences
Galapagos NV
Ono Pharmaceutical Co. Ltd
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol  [PDF] July 12, 2018
Statistical Analysis Plan  [PDF] May 30, 2019

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT03100942    
Other Study ID Numbers: GS-US-445-4189
2016-003558-34 ( EudraCT Number )
First Posted: April 4, 2017    Key Record Dates
Results First Posted: January 22, 2020
Last Update Posted: October 23, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Sjogren's Syndrome
Syndrome
Disease
Pathologic Processes
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Xerostomia
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Dry Eye Syndromes
Lacrimal Apparatus Diseases
Eye Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases