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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 67
- 试验地点
- 74
- 主要终点
- Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 20% Improvement Response at Week 12
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meet Classification Criteria for Psoriatic Arthritis (CASPAR) and have a history consistent with psoriatic arthritis (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
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Filgotinib (Drug)
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.
干预措施: Placebo to match filgotinib (Drug)
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.
干预措施: Placebo to match adalimumab (Drug)
Filgotinib 100 mg (Main Study)
Participants will receive PTM filgotinib 200 mg + filgotinib 100 mg + PTM adalimumab for up to 16 weeks.
干预措施: Filgotinib (Drug)
Filgotinib 100 mg (Main Study)
Participants will receive PTM filgotinib 200 mg + filgotinib 100 mg + PTM adalimumab for up to 16 weeks.
干预措施: Placebo to match filgotinib (Drug)
Filgotinib 100 mg (Main Study)
Participants will receive PTM filgotinib 200 mg + filgotinib 100 mg + PTM adalimumab for up to 16 weeks.
干预措施: Placebo to match adalimumab (Drug)
Adalimumab (Main Study)
Participants will receive PTM filgotinib 200 mg + PTM filgotinib 100 mg + adalimumab 40 mg injection for up to 16 weeks.
干预措施: Adalimumab (Drug)
Adalimumab (Main Study)
Participants will receive PTM filgotinib 200 mg + PTM filgotinib 100 mg + adalimumab 40 mg injection for up to 16 weeks.
干预措施: Placebo to match filgotinib (Drug)
Placebo (Main Study)
Participants will receive PTM filgotinib 200 mg + PTM filgotinib 100 mg + PTM adalimumab injection for up to 16 weeks.
干预措施: Placebo to match filgotinib (Drug)
Placebo (Main Study)
Participants will receive PTM filgotinib 200 mg + PTM filgotinib 100 mg + PTM adalimumab injection for up to 16 weeks.
干预措施: Placebo to match adalimumab (Drug)
Filgotinib 200 mg (Long Term Extension [LTE])
Participants will receive filgotinib 200 mg + PTM filgotinib 100 mg for up to 34 weeks.
干预措施: Filgotinib (Drug)
Filgotinib 200 mg (Long Term Extension [LTE])
Participants will receive filgotinib 200 mg + PTM filgotinib 100 mg for up to 34 weeks.
干预措施: Placebo to match filgotinib (Drug)
Filgotinib 100 mg (LTE)
Participants will receive PTM filgotinib 200 mg + filgotinib 100 mg for up to 34 weeks.
干预措施: Filgotinib (Drug)
Filgotinib 100 mg (LTE)
Participants will receive PTM filgotinib 200 mg + filgotinib 100 mg for up to 34 weeks.
干预措施: Placebo to match filgotinib (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 20% Improvement Response at Week 12
时间窗: Week 12
ACR20 response is achieved when the participant has: ≥ 20% improvement (reduction) from baseline in tender joint count based on 68 joints (TJC68), swollen joint count based on 66 joints (SJC66) and in at least 3 of the following 5 items: patient's global assessment of disease activity (PGADA) using a visual analogue scale (VAS) on a scale of 0 (very well) to 100 (very poor); physician's global assessment of disease activity (PHGADA) using a VAS on a scale of 0 (no disease activity) to 100 (maximum disease activity); health assessment questionnaire-disability index (HAQ-DI) inclusive of activities scored on a scale of 0 (no disability) to 3 (completely disabled); HAQ-DI pain assessment using VAS on a scale of 0 (no pain) to 100 (serious pain), and high-sensitivity C-reactive protein (hsCRP).
次要结局
- Percentage of Participants Who Achieved Very Low Disease Activity (VLDA) Response at Weeks 4, 8, 12, and 16(Weeks 4, 8, 12, and 16)
- Change From Baseline in Leeds Enthesitis Index (LEI) at Weeks 4, 8, 12, and 16 in Participants With Enthesitis at Baseline(Baseline, 4, 8, 12, and 16 weeks)
- Change From Baseline in Psoriatic Arthritis Disease Activity Score (PASDAS) at Weeks 4 and 16(Baseline, 4, and 16 weeks)
- Change From Baseline in Modified Nail Psoriasis Severity Index (mNAPSI) at Weeks 4, 8, 12, and 16 in Participants With Psoriatic Nail Involvement at Baseline(Baseline, 4, 8, 12, and 16 weeks)
- Percentage of Participants Who Achieved Minimal Disease Activity (MDA) Response at Weeks 4, 8, 12, and 16(Weeks 4, 8, 12, and 16)
- Change From Baseline in Disease Activity in Psoriatic Arthritis (DAPSA) at Weeks 2, 4, 8, 12, and 16(Baseline, 2, 4, 8, 12, and 16 weeks)
- Percentage of Participants Who Achieved an American College of Rheumatology 20% Improvement Response at Weeks 2, 4, 8, 12, and 16(Weeks 2, 4, 8, 12, and 16)
- Percentage of Participants Who Achieved an American College of Rheumatology 70% Improvement Response at Weeks 2, 4, 8, 12, and 16(Weeks 2, 4, 8, 12, and 16)
- Change From Baseline in Physician's Global Assessment of Psoriasis (PhGAP) at Weeks 2, 4, 8, 12, and 16 in Participants With Psoriasis Covering ≥ 3% of the Body Surface Area (BSA) at Baseline(Baseline, 2, 4, 8, 12, and 16 weeks)
- Percentage of Participants Who Achieved an American College of Rheumatology 50% Improvement Response at Weeks 2, 4, 8, 12, and 16(Weeks 2, 4, 8, 12, and 16)
- Change From Baseline in Individual ACR Component: Physician's Global Assessment of Disease Activity (PhGADA) at Weeks 2, 4, 8, 12, and 16(Baseline, 2, 4, 8, 12, and 16 weeks)
- Change From Baseline in Individual ACR Component: Health Assessment Questionnaire Disability Index (HAQ-DI)'s Pain Assessment at Weeks 2, 4, 8, 12, and 16(Baseline, 2, 4, 8, 12, and 16 weeks)
- Percentage of Participants Who Achieved DAPSA LDA at Weeks 2, 4, 8, 12, and 16(Weeks 2, 4, 8, 12, and 16)
- Percentage of Participants Who Achieved Psoriasis Area and Severity Index 75% Improvement (PASI75) Response at Weeks 4, 8, 12, and 16 in Participants With Psoriasis Covering ≥ 3% of the BSA at Baseline(Weeks 4, 8, 12, and 16)
- Percentage of Participants With PASDAS Low Disease Activity (LDA) at Weeks 4 and 16(Weeks 4, and 16)
- Percentage of Participants Who Achieved PASDAS Remission at Weeks 4 and 16(Weeks 4, and 16)
- Change From Baseline in Individual ACR Component: Tender Joint Count Based on 68 Joints (TJC68) at Weeks 2, 4, 8, 12, and 16(Baseline, 2, 4, 8, 12, and 16 weeks)
- Percentage of Participants Who Achieved DAS28(CRP) LDA at Weeks 2, 4, 8, 12, and 16(Weeks 2, 4, 8, 12, and 16)
- Percentage of Participants Who Achieved DAS28 (CRP) Remission at Weeks 2, 4, 8, 12, and 16(Weeks 2, 4, 8, 12, and 16)
- Change From Baseline in 12-Item Psoriatic Arthritis Impact of Disease (PsAID-12) Score at Weeks 4 and 16(Baseline, 4, and 16 weeks)
- Change From Baseline in ACR Component: Swollen Joint Count Based on 66 Joints (SJC66) at Weeks 2, 4, 8, 12, and 16(Baseline, 2, 4, 8, 12, and 16 weeks)
- Change From Baseline in Individual ACR Component: Patient's Global Assessment of Disease Activity (PGADA) at Weeks 2, 4, 8, 12, and 16(Baseline, 2, 4, 8, 12, and 16 weeks)
- Change From Baseline in Disease Activity Score 28 (DAS28) C-Reactive Protein (CRP) at Weeks 2, 4, 8, 12, and 16(Baseline, 2, 4, 8, 12, and 16 weeks)
- Time to Achieve DAS28 (CRP) LDA(Up to 19 weeks)
- Percentage of Participants Who Achieved Psoriatic Arthritis Response Criteria (PsARC) Response at Weeks 2, 4, 8, 12, and 16(Weeks 2, 4, 8, 12, and 16)
- Change From Baseline in Psoriasis Area and Severity Index (PASI) at Weeks 4, 8, 12, and 16 in Participants With Psoriasis Covering ≥ 3% of the BSA at Baseline(Baseline, 4, 8, 12, and 16 weeks)
- Change From Baseline in Individual ACR Component: High-Sensitivity C-Reactive Protein (hsCRP) at Weeks 2, 4, 8, 12, and 16(Baseline, 2, 4, 8, 12, and 16 weeks)
- Percentage of Participants Who Achieved Psoriasis Area and Severity Index 90% Improvement (PASI90) Response at Weeks 4, 8, 12, and 16 in Participants With Psoriasis Covering ≥ 3% of the BSA at Baseline(Weeks 4, 8, 12, and 16)
- Change From Baseline in Mental Component Score (MCS) of the 36-Item Short-Form Version 2 (SF-36v2) at Weeks 4 and 16(Baseline, 4, and 16 weeks)
- Time to Achieve DAPSA LDA(Up to 19 weeks)
- Percentage of Participants Who Achieved Psoriasis Area and Severity Index 50% Improvement (PASI50) Response at Weeks 4, 8, 12, and 16 in Participants With Psoriasis Covering ≥ 3% of the BSA at Baseline(Weeks 4, 8, 12, and 16)
- Change From Baseline in Leeds Dactylitis Index (LDI) at Weeks 4, 8, 12, and 16 in Participants With Dactylitis at Baseline(Baseline, 4, 8, 12, and 16 weeks)
- Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Weeks 2, 4, 8, 12, and 16(Baseline, 2, 4, 8, 12, and 16 weeks)
- Percentage of Participants Who Achieved DAPSA Remission at Weeks 2, 4, 8, 12, and 16(Weeks 2, 4, 8, 12, and 16)
- Percentage of Participants Who Achieved Psoriasis Area and Severity Index 100% Improvement (PASI100) Response at Weeks 4, 8, 12, and 16 in Participants With Psoriasis Covering ≥ 3% of the BSA at Baseline(Weeks 4, 8, 12, and 16)
- Change From Baseline in Tender Dactylitis Count (TDC) at Weeks 4, 8, 12, and 16 in Participants With Dactylitis at Baseline(Baseline, 4, 8, 12, and 16 weeks)
- Change From Baseline in Physical Component Score (PCS) of the SF-36v2 at Weeks 4 and 16(Baseline, 4, and 16 weeks)
- Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index at Weeks 4, 8, 12, and 16 in Participants With Enthesitis at Baseline(Baseline, 4, 8, 12, and 16 weeks)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) Score at Weeks 4 and 16(Baseline, 4, and 16 weeks)