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Study to Evaluate the Efficacy and Safety of Filgotinib in Participants With Active Psoriatic Arthritis Who Are Naive to Biologic DMARD Therapy (PENGUIN 1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04115748
Recruitment Status : Active, not recruiting
First Posted : October 4, 2019
Last Update Posted : June 25, 2020
Sponsor:
Collaborator:
Galapagos NV
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
The primary objective of this study is to evaluate the effect of filgotinib compared to placebo as assessed by the American College of Rheumatology 20% improvement (ACR20) response in participants with active psoriatic arthritis who are naive to biologic disease-modifying anti-rheumatic drug (DMARD) therapy. The study consists of two parts, the Main Study and the Long Term Extension (LTE).

Condition or disease Intervention/treatment Phase
Psoriatic Arthritis Drug: Filgotinib Drug: Adalimumab Drug: Placebo to match filgotinib Drug: Placebo to match adalimumab Phase 3

Detailed Description:
28April2020: The study recruitment is currently on pause due to the coronavirus disease (COVID-19) pandemic. The overall status will be updated when the study begins recruiting again

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 854 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Placebo and Adalimumab-controlled Study to Evaluate the Efficacy and Safety of Filgotinib in Subjects With Active Psoriatic Arthritis Who Are Naive to Biologic DMARD Therapy
Actual Study Start Date : December 3, 2019
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : May 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Adalimumab

Arm Intervention/treatment
Experimental: Filgotinib 200 mg (Main Study)
Participants will receive filgotinib 200 mg + placebo to match (PTM) filgotinib 100 mg + PTM adalimumab injection for up to 16 weeks.
Drug: Filgotinib
Tablets administered orally once daily with or without food
Other Names:
  • GS-6034
  • GLPG0634

Drug: Placebo to match filgotinib
Tablets administered orally once daily with or without food

Drug: Placebo to match adalimumab
Injection administered subcutaneously once every 2 weeks

Experimental: Filgotinib 100 mg (Main Study)
Participants will receive PTM filgotinib 200 mg + filgotinib 100 mg + PTM adalimumab for up to 16 weeks.
Drug: Filgotinib
Tablets administered orally once daily with or without food
Other Names:
  • GS-6034
  • GLPG0634

Drug: Placebo to match filgotinib
Tablets administered orally once daily with or without food

Drug: Placebo to match adalimumab
Injection administered subcutaneously once every 2 weeks

Active Comparator: Adalimumab (Main Study)
Participants will receive PTM filgotinib 200 mg + PTM filgotinib 100 mg + adalimumab 40 mg injection for up to 16 weeks.
Drug: Adalimumab
Injection administered subcutaneously once every 2 weeks

Drug: Placebo to match filgotinib
Tablets administered orally once daily with or without food

Placebo Comparator: Placebo (Main Study)
Participants will receive PTM filgotinib 200 mg + PTM filgotinib 100 mg + PTM adalimumab injection for up to 16 weeks.
Drug: Placebo to match filgotinib
Tablets administered orally once daily with or without food

Drug: Placebo to match adalimumab
Injection administered subcutaneously once every 2 weeks

Experimental: Filgotinib 200 mg (LTE)
Participants will receive filgotinib 200 mg + PTM filgotinib 100 mg for up to 2 years.
Drug: Filgotinib
Tablets administered orally once daily with or without food
Other Names:
  • GS-6034
  • GLPG0634

Drug: Placebo to match filgotinib
Tablets administered orally once daily with or without food

Experimental: Filgotinib 100 mg (LTE)
Participants will receive PTM filgotinib 200 mg + filgotinib 100 mg for up to 2 years.
Drug: Filgotinib
Tablets administered orally once daily with or without food
Other Names:
  • GS-6034
  • GLPG0634

Drug: Placebo to match filgotinib
Tablets administered orally once daily with or without food




Primary Outcome Measures :
  1. Percentage of Participants who Achieve an American College of Rheumatology (ACR) 20% Improvement Response at Week 12 [ Time Frame: Week 12 ]
    ACR20 is calculated as an at least 20% improvement from baseline in both tender and swollen joint counts and an at least 20% improvement in at least 3 of the following 5 measures: participant's global assessment of disease activity, physician's global assessment of disease activity, participant's assessment of pain, health assessment questionnaire - disability index (HAQ-DI) and an acute-phase reactant high sensitivity C-reactive protein (hsCRP).


Secondary Outcome Measures :
  1. Change from Baseline in Psoriatic Arthritis Disease Activity Score (PASDAS) [ Time Frame: Baseline; Weeks 4, 16 ]
    PASDAS is a composite disease activity measure for psoriatic arthritis. The PASDAS covers the physician's global assessment of disease activity and participant's global assessment of disease activity, the Short-Form Health Survey (SF-36) Physical Component Score (PCS), swollen and tender joint counts, enthesitis and dactylitis, as well as hsCRP. A lower score indicates better function.

  2. Percentage of Participants who Achieved Minimal Disease Activity (MDA) Response [ Time Frame: Weeks 4, 8, 12, 16 ]
    Minimal disease activity will be determined by tender and swollen joint counts, PASI or body surface area (BSA), participant's assessment of pain, participant's global assessment of disease activity, HAQ-DI, and SPARCC Enthesitis Index.

  3. Percentage of Participants who Achieved Very Low Disease Activity (VLDA) Response [ Time Frame: Weeks 4, 8, 12, 16 ]
    VLDA will be determined by tender and swollen joint counts, PASI or BSA, participant's assessment of pain, participant's global assessment of disease activity, HAQ-DI, and SPARCC Enthesitis Index.

  4. Change from Baseline in Disease Activity in Psoriatic Arthritis (DAPSA) [ Time Frame: Baseline; Weeks 2, 4, 8, 12, 16 ]
    DAPSA is a psoriatic arthritis disease activity measure, calculated by summing swollen and tender joint counts, participant's assessment of pain, participant's global assessment of disease activity, and hsCRP.

  5. Change from Baseline in Physician's Global Assessment of Psoriasis (PhGAP) in Participants with Psoriasis Covering ≥ 3% of the BSA at Baseline [ Time Frame: Baseline; Weeks 2, 4, 8, 12, 16 ]
    The physician's global assessment of psoriasis is used to determine the participant's psoriasis lesions overall at a given time point. The participant's psoriasis disease activity will be assessed by a physician, using a 6-point scale, which ranges from 0 (cleared) to 5 (severe).

  6. Change from Baseline in Modified Nail Psoriasis Severity Index (mNAPSI) in Participants with Psoriatic Nail Involvement at Baseline [ Time Frame: Baseline; Weeks 4, 8, 12, 16 ]
    Each fingernail was assessed for psoriasis with mNAPSI, and the scores of all 10 fingernails were combined. Investigators assessed each nail abnormality for each of a participant's nails by grading 3 features or groups of features (pitting, onycholysis and oil-drop dyschromia, and crumbling) and noting the presence or absence of 4 features (leukonychia, splinter hemorrhages, hyperkeratosis, and red spots in the lunula). The range of possible scores was 0 to 130, with a score of 0 indicating absence of nail psoriasis and a score of 130 indicating the most severe nail psoriasis. A decrease in mNAPSI score indicates improvement.

  7. Change from Baseline in Leeds Enthesitis Index (LEI) in Participants with Enthesitis at Baseline [ Time Frame: Baseline; Weeks 4, 8, 12, 16 ]
    Enthesitis will be assessed using LEI. The LEI was developed to assess enthesitis in participants with PsA, and evaluates the presence (score of 1) or absence of pain (score of 0) by applying local pressure to Lateral elbow epicondyle, left and right, Medial femoral condyle, left and right, and Achilles tendon insertion, left and right. LEI scores ranging from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness).

  8. Change from Baseline in 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) [ Time Frame: Baseline; Weeks 4, 16 ]
    The PsAID questionnaire assesses the impact of PsA on people's lives. It is a 12-item questionnaire, where each item will be scored between 0 and 10. All items are prioritized according to importance of the health domain it represents. A higher score on the PsAID indicates more impact of the disease.

  9. Percentage of Participants with Psoriatic Arthritis Disease Activity Score (PASDAS) Low Disease Activity (LDA) [ Time Frame: Baseline; Weeks 4, 16 ]
    PASDAS LDA is defined as PASDAS ≤ 3.2.

  10. Percentage of Participants who Achieve PASDAS Remission [ Time Frame: Baseline; Weeks 4, 16 ]
    PASDAS remission is defined as PASDAS ≤ 1.9.

  11. Percentage of Participants who Achieve an American College of Rheumatology 20% Improvement Response [ Time Frame: Baseline; Weeks 2, 4, 8, 16 ]
    ACR20 is calculated as an at least 20% improvement from baseline in both tender and swollen joint counts and an at least 20% improvement in at least 3 of the following 5 measures: participant's global assessment of disease activity, physician's global assessment of disease activity, participant's assessment of pain, HAQ-DI and an acute-phase reactant hsCRP.

  12. Percentage of Participants who Achieve an American College of Rheumatology 50% Improvement Response [ Time Frame: Weeks 2, 4, 8, 12, 16 ]
    ACR50 is calculated as an at least 50% improvement from baseline in both tender and swollen joint counts and an at least 50% improvement in at least 3 of the following 5 measures: participant's global assessment of disease activity, physician's global assessment of disease activity, participant's assessment of pain, HAQ-DI, and an acute-phase reactant hsCRP.

  13. Percentage of Participants who Achieve an American College of Rheumatology 70% Improvement Response [ Time Frame: Baseline; Weeks 2, 4, 8, 12, 16 ]
    ACR70 is calculated as an at least 70% improvement from baseline in both tender and swollen joint counts and an at least 70% improvement in at least 3 of the following 5 measures: participant's global assessment of disease activity, physician's global assessment of disease activity, participant'ss assessment of pain, HAQ-DI and an acute-phase reactant (high sensitivity C-reactive protein [hsCRP]).

  14. Change from Baseline in Individual Components of the American College of Rheumatology Response Criteria [ Time Frame: Baseline; Weeks 2, 4, 8, 12, 16 ]
    Components of ACR include tender and swollen joint counts, participant's global assessment of disease activity, physician's global assessment of disease activity, participant's assessment of pain, HAQ-DI and hsCRP.

  15. Change from Baseline in Participants who Achieve Disease Activity Score 28 (DAS28) C-Reactive Protein (CRP) [ Time Frame: Baseline; Weeks 2, 4, 8, 12, 16 ]
    DAS28(CRP) is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), participant's global assessment of disease activity and hsCRP. Higher values indicate higher disease activity. A negative change from baseline indicates improvement.

  16. Percentage of Participants who Achieve DAS28(CRP) LDA [ Time Frame: Baseline; Weeks 2, 4, 8, 12, 16 ]
    DAS28(CRP) LDA is defined as DAS28(CRP) ≤ 3.2.

  17. Percentage of Participants who Achieve DAS28(CRP) Remission [ Time Frame: Baseline; Weeks 2, 4, 8, 12, 16 ]
    DAS28(CRP) remission is defined as DAS28(CRP) < 2.6.

  18. Time to Achieve DAS28(CRP) LDA [ Time Frame: First dose date up to 16 weeks ]
    Time to achieve DAS28(CRP) LDA is the number of days from the first dose date of study drug administration to the first time when a participant achieves DAS28(CRP) LDA, or censored if a participant does not achieve DAS28(CRP) LDA or missing.

  19. Percentage of Participants who Achieve DAPSA LDA [ Time Frame: Baseline; Weeks 2, 4, 8, 12, 16 ]
    DAPSA LDA is defined as DAPSA ≤ 14.

  20. Percentage of Participants who Achieve DAPSA Remission [ Time Frame: Baseline; Weeks 2, 4, 8, 12, 16 ]
    DAPSA remission is defined as DAPSA ≤ 4.

  21. Time to Achieve DAPSA LDA [ Time Frame: First dose date up to 16 weeks ]
    Time to achieve DAPSA LDA is the number of days from the first dose date of study drug administration to the first time when a participant achieves DAPSA LDA, or censored if a participant does not achieve DAPSA LDA or missing.

  22. Percentage of Participants who Achieve Psoriatic Arthritis Response Criteria (PsARC) Response [ Time Frame: Baseline; Weeks 2, 4, 8, 12, 16 ]
    PsARC consists of four components: assessment of joint tenderness and swelling utilizing 68/66 joint counts respectively, participant's global assessment of disease activity, and physician's global assessment of disease activity.

  23. Change from Baseline in Psoriasis Area and Severity Index (PASI) in Participants with Psoriasis Covering ≥ 3% of the BSA at Baseline [ Time Frame: Baseline; Weeks 4, 8, 12, 16 ]
    PASI will be assessed in participants with psoriasis covering ≥ 3% of the BSA at Baseline. PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head and neck, trunk, upper limbs, and lower limbs. Each of these areas are assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percent [%] to 100% involvement), and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 (no psoriasis) to 72. A higher score indicates more severe disease.

  24. Percentage of Participants who Achieve Psoriasis Area and Severity Index 50% Improvement (PASI50) Response [ Time Frame: Weeks 4, 8, 12, 16 ]
    The PASI50 will be assessed in participants with psoriasis covering ≥ 3% of the BSA at Baseline. A PASI50 response represents at least a 50% improvement from baseline in the PASI score.

  25. Percentage of Participants who Achieve Psoriasis Area and Severity Index 75% Improvement (PASI75) Response with Psoriasis Covering ≥ 3% of the Body Surface Area [ Time Frame: Weeks 4, 8, 12, 16 ]
    The PASI75 will be assessed in participants with psoriasis covering ≥ 3% of the BSA at Baseline. A PASI75 response represents at least a 75% improvement from baseline in the PASI score.

  26. Percentage of Participants who Achieve Psoriasis Area and Severity Index 90% Improvement (PASI90) Response [ Time Frame: Weeks 4, 8, 12, 16 ]
    The PASI90 will be assessed in participants with psoriasis covering ≥ 3% of the BSA at Baseline. A PASI90 response represents at least a 90% improvement from baseline in the PASI score.

  27. Percentage of Participants who Achieve Psoriasis Area and Severity Index 100% Improvement (PASI100) Response [ Time Frame: Weeks 4, 8, 12, 16 ]
    The PASI100 will be assessed in participants with psoriasis covering ≥ 3% of the BSA at Baseline. A PASI100 response represents a 100% improvement from baseline in the PASI score.

  28. Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index in Participants with Enthesitis at Baseline [ Time Frame: Baseline; Weeks 4, 8, 12, 16 ]
    The SPARCC Enthesitis Index identifies the presence or absence of tenderness at 16 enthesial sites, including the bilateral Achilles tendons, plantar fascia insertion at the calcaneus, patellar tendon insertion at the base of the patella, quadriceps insertion into the superior border of the patella, supraspinatus insertion into the greater tuberosity of the humerus, and medial and lateral epicondyles. Tenderness is quantified as present (1) or absent (0) for each of the 16 sites, with an overall total score ranging from 0 to 16. Higher score indicates a greater number of sites that are affected by enthesitis.

  29. Change from Baseline in Leeds Dactylitis Index (LDI) in Participants with Dactylitis at Baseline [ Time Frame: Baseline; Weeks 4, 8, 12, 16 ]
    LDI quantitatively measures dactylitis using the circumference of involved digits and control digits and tenderness of involved digits. Digits affected by dactylitis are defined as those with an at least 10% difference in the ratio of circumference of the affected digit to the contralateral digit. The control digit is either the contralateral digit (digit on opposite hand or foot), or if the contralateral digit is also affected, values from a standard reference table. Tenderness of affected digits is assessed on a scale from 0 [no tenderness] to 3 [tender and withdrawn]. A higher LDI indicates worse dactylitis.

  30. Change from Baseline in Tender Dactylitis Count (TDC) [ Time Frame: Baseline; Weeks 4, 8, 12, 16 ]
    TDC will be assessed in participants with dactylitis at Baseline. TDC is a simple count based on the presence or absence of tender joints.

  31. Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) [ Time Frame: Baseline; Weeks 2, 4, 8, 12, 16 ]
    HAQ-DI is used to monitor the participant's self-assessed physical function or disability. This 20 -question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 function areas (getting dressed, arising, eating, walking, hygiene, reaching, gripping, and activities). HAQ-DI total score ranges from 0 to 3, with higher scores indicating greater dysfunction.

  32. Change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) [ Time Frame: Baseline; Weeks 4, 16 ]
    FACIT-Fatigue is a 13-item questionnaire, with each item scored on a 5-point scale ranging from 0 (not at all) to 4 (very much). FACIT-Fatigue total score ranges 0 to 52. Higher scores represent better fatigue status.

  33. Change From Baseline in Mental Component Score (MCS) and Physical Component Score (PCS) of the Medical Outcomes SF-36 Version 2 [ Time Frame: Baseline; Weeks 4, 16 ]
    Composite endpoint of change from baseline in MCS and PCS scores in SF-36 Version 2. The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and 2 component scores (MCS and PCS). MCS consists of social functioning, vitality, mental health, and role-emotional scales. PCS consists of physical functioning, bodily pain, role-physical, and general health scales. Each domain will be scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Meet Classification Criteria for Psoriatic Arthritis (CASPAR) and have a history consistent with PsA ≥ 6 months at Screening
  • Have active PsA defined as ≥ 3 swollen joints (from a 66 swollen joint count [SJC]) and ≥ 3 tender joints (from a 68 tender joint count [TJC]) at Screening and Day 1; these may or may not be the same joints at Screening and Day 1
  • Must have a documented history or active signs of at least one of the following at Screening:

    • Plaque psoriasis
    • Nail changes attributed to psoriasis
  • Have had inadequate response or intolerance to ≥1 conventional synthetic disease-modifying anti-rheumatic drug (csDMARD), apremilast and / or NSAID, administered over the course of ≥ 12 weeks for the treatment of PsA, as per local guidelines / standard of care

Key Exclusion Criteria:

  • Prior PsA or psoriasis treatment with a biologic DMARD
  • Prior exposure to a janus kinase (JAK) inhibitor > 2 doses
  • Any active / recent infection
  • Any chronic and / or uncontrolled medical condition that would put the individual at increased risk during study participation or circumstances which may make an individual unlikely or unable to complete or comply with study procedures and requirements, per investigator judgement
  • Any moderately to severely active musculoskeletal or skin disorder other than PsA or plaque psoriasis that would interfere with assessment of study parameters, as per judgement of investigator

NOTE: Prior history of reactive arthritis or axial spondyloarthritis is permitted if there is documentation of change in diagnosis to PsA or additional diagnosis of PsA

  • Any history of an inflammatory arthropathy with onset before age 16 years old
  • Active autoimmune disease that would interfere with assessment of study parameters or increase risk to the individual by participating in the study (e.g. uveitis, inflammatory bowel disease, uncontrolled thyroiditis, systemic vasculitis, transverse myelitis), per judgement of investigator
  • Pregnancy or nursing females
  • Active drug or alcohol abuse, as per judgement of investigator

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): NCT04115748


Locations
Show Show 18 study locations
Sponsors and Collaborators
Gilead Sciences
Galapagos NV
Investigators
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Study Director: Gilead Study Director Gilead Sciences
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT04115748    
Other Study ID Numbers: GS-US-431-4566
2019-001996-35 ( EudraCT Number )
JapicCTI-205202 ( Registry Identifier: JapicCTI )
First Posted: October 4, 2019    Key Record Dates
Last Update Posted: June 25, 2020
Last Verified: June 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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Arthritis
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents