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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
Show Show 53 study locations
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