A Multicenter, Randomized, Double-Blind, Placebo Controlled 24-Week Study Followed by Long Term Evaluation of Efficacy and Safety of Ixekizumab (LY2439821) in Biologic Disease-Modifying Antirheumatic Drug-Experienced Patients With Active Psoriatic Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 363
- 试验地点
- 105
- 主要终点
- Percentage of Participants Achieving American College of Rheumatology 20 Index (ACR20)
研究概览
简要总结
The main purpose of this study is to evaluate how effective and safe the study drug known as ixekizumab is in participants with active psoriatic arthritis.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Presents with established diagnosis of active psoriatic arthritis (PsA) for at least 6 months, and currently meets Classification for Psoriatic Arthritis (CASPAR) criteria
- •Active PsA defined as the presence of at least 3 tender and at least 3 swollen joints
- •Presence of active psoriatic skin lesion or a history of plaque psoriasis (Ps)
- •Men must agree to use a reliable method of birth control or remain abstinent during the study
- •Women must agree to use reliable birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment
- •Have been treated with 1 or more conventional disease-modifying antirheumatic drugs (cDMARDs)
- •Have had prior treatment with at least 1 and not more than 2 tumor necrosis factor (TNF) inhibitors. The participant must have discontinued at least 1 TNF inhibitor due to either an inadequate response (based on a minimum of 12 weeks on therapy) or documented intolerance.
排除标准
- •Current use of biologic agents for treatment of Ps or PsA
- •Inadequate response to greater than 2 biologic DMARDs
- •Current use of more than one cDMARDs
- •Diagnosis of active inflammatory arthritic syndromes or spondyloarthropathies other than PsA
- •Have received treatment with interleukin (IL) -17 or IL12/23 targeted monoclonal antibody (MAb) therapy
- •Serious disorder or illness other than psoriatic arthritis
- •Serious infection within the last 3 months
- •Breastfeeding or nursing (lactating) women
研究组 & 干预措施
Ixekizumab 80 milligram (mg) every 2 Weeks (Q2W)
Blinded Treatment Period (Week(wk) 0-24): Participants (pts) received a starting dose of 160 mg of ixekizumab (ixe) given as 2 subcutaneous (SC) injections at Wk 0 followed by 1 SC injection of 80 mg of ixe Q2W given on Wks 2,4,6,8,10,12,14,16,18,20,22, and 24.Week 16 inadequate responders (IR) from the placebo treatment group who were re-randomized (1:1) to ixe 80 mg Q2W and IR from ixekizumab 80 mg Q2W who continued on ixekizumab 80 mg Q2W. Pts receive rescue therapy while receiving ixekizumab given as 1 injection of 80 mg Q2W given on Wks 16,18,20,22,24. Extension Period (Wk24-156):Pts who were randomized to ixe 80 mg Q2W at week 0 and continued on ixe 80 mg Q2W during the Extension Period. Pts who received ixekizumab 80 mg Q2W,who were either completed the study or discontinued the study early entered the post-treatment follow-up period (12-24 weeks).
干预措施: Placebo (Drug)
Ixekizumab 80 milligram (mg) every 2 Weeks (Q2W)
Blinded Treatment Period (Week(wk) 0-24): Participants (pts) received a starting dose of 160 mg of ixekizumab (ixe) given as 2 subcutaneous (SC) injections at Wk 0 followed by 1 SC injection of 80 mg of ixe Q2W given on Wks 2,4,6,8,10,12,14,16,18,20,22, and 24.Week 16 inadequate responders (IR) from the placebo treatment group who were re-randomized (1:1) to ixe 80 mg Q2W and IR from ixekizumab 80 mg Q2W who continued on ixekizumab 80 mg Q2W. Pts receive rescue therapy while receiving ixekizumab given as 1 injection of 80 mg Q2W given on Wks 16,18,20,22,24. Extension Period (Wk24-156):Pts who were randomized to ixe 80 mg Q2W at week 0 and continued on ixe 80 mg Q2W during the Extension Period. Pts who received ixekizumab 80 mg Q2W,who were either completed the study or discontinued the study early entered the post-treatment follow-up period (12-24 weeks).
干预措施: Ixekizumab 80 mg Q2W (Drug)
Ixekizumab 80 mg Q4W
Blinded Treatment Period (Week 0-24): Participants (pts) received a starting dose of 160 mg of ixekizumab (ixe) given as 2 subcutaneous (SC) injections at Wk 0 followed by 1 SC injection of 80 mg of ixe Q4W given on Wks 4, 8 and 12 alternating with placebo for ixe injections Q4W given on Wks 2,6,10,14,18, and 22.Week 16 inadequate responders (IR) from the placebo treatment group who were re-randomized (1:1) to ixe 80 mg Q4W and IR from ixekizumab 80 mg Q4W who continued on ixekizumab 80 mg Q4W. Pts receive rescue therapy while receiving ixekizumab given as 1 injection of 80 mg Q4W given on Wks 16 and 20 alternating with placebo for ixe injections Q4W given on Wks 18 and 22.Extension Period (Wk24-156):Pts who were randomized to ixe 80 mg Q4W at week 0 and continued on ixe 80 mg Q4W during the Extension Period.Pts who received ixekizumab 80 mg Q4W,who were either completed the study or discontinued the study early entered the post-treatment follow-up period (12-24 weeks).
干预措施: Placebo (Drug)
Ixekizumab 80 mg Q4W
Blinded Treatment Period (Week 0-24): Participants (pts) received a starting dose of 160 mg of ixekizumab (ixe) given as 2 subcutaneous (SC) injections at Wk 0 followed by 1 SC injection of 80 mg of ixe Q4W given on Wks 4, 8 and 12 alternating with placebo for ixe injections Q4W given on Wks 2,6,10,14,18, and 22.Week 16 inadequate responders (IR) from the placebo treatment group who were re-randomized (1:1) to ixe 80 mg Q4W and IR from ixekizumab 80 mg Q4W who continued on ixekizumab 80 mg Q4W. Pts receive rescue therapy while receiving ixekizumab given as 1 injection of 80 mg Q4W given on Wks 16 and 20 alternating with placebo for ixe injections Q4W given on Wks 18 and 22.Extension Period (Wk24-156):Pts who were randomized to ixe 80 mg Q4W at week 0 and continued on ixe 80 mg Q4W during the Extension Period.Pts who received ixekizumab 80 mg Q4W,who were either completed the study or discontinued the study early entered the post-treatment follow-up period (12-24 weeks).
干预措施: Ixekizumab 80 mg Q4W (Drug)
Placebo
Blinded Treatment Period (Wk 0-24): Pts received placebo for Ixe as 2 SC injections followed by 1 SC injection Q2W given on Wks 2,4,6,8,10,12,14,16,18,20,22 and 24. Pts initially randomized to placebo treatment group in the double blind treatment period,flagged as IR at Wk 16,re-randomized to ixe 80 mg Q2W/Q4W for the remainder of the current period and following period. Extended Treatment Period (Wk 24-156): Pts who were randomized to placebo at Week 0 then randomized to ixekizumab 80 mg Q2W/Q4W during the Extension Period.Pts who remained on placebo at the completion of the double blind treatment period received the first dose of ixe (160 mg starting dose) at Wk 24.Pts who were IRs at Wk 16 and were re-randomized to ixe at Wk 16 received the first dose of ixe (160 mg starting dose) at Wk 16. Pts who received placebo,who were either completed the study or discontinued the study early entered the post-treatment follow-up period (12-24 weeks).
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Achieving American College of Rheumatology 20 Index (ACR20)
时间窗: Week 24
ACR20 response is defined as a greater than or equal to (≥) 20% improvement from baseline for tender joint count (TJC) and swollen joint count (SJC) and in at least 3 of the following 5 criteria: Participant's assessment of Joint Pain visual analog scale (VAS), Participant's Global Assessment of Disease Activity VAS (PatGA), Physician's Global Assessment of the Disease Activity VAS (PGA), Participant's Assessment of Physical Function using the Health Assessment Questionnaire Disability Index (HAQ-DI), or Acute Phase Reactant as measured by high sensitivity C-reactive protein (hs-CRP).
次要结局
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score(Baseline, Week 24)
- Percentage of Participants Achieving ACR20(Week 12)
- Percentage of Participants Achieving American College of Rheumatology 50 Index (ACR50)(Week 24)
- Percentage of Participants Achieving American College of Rheumatology 70 Index (ACR70)(Week 24)
- Percentage of Participants With Psoriasis Area and Severity Index (PASI) 75(Week 12)
- Percentage of Patients Achieving Minimal Disease Activity (MDA)(Week 24)
- Percentage of Patients Achieving Complete Resolution in Enthesitis as Assessed by the Leeds Enthesitis Index (LEI)(Week 24)
- Change From Baseline in Itch Numeric Rating Scale (NRS)(Baseline, Week 12)
- Percentage of Participants Achieving ACR 70(Week 52 and Week 156)
- Change From Baseline in Tender Joint Count (TJC)(Baseline, Week 24)
- Change From Baseline in Swollen Joint Count (SJC)(Baseline, Week 24)
- Change From Baseline in Participants Assessment of Pain Visual Analog Scale (VAS)(Baseline, Week 24)
- Change From Baseline in Patients Global Assessment of Disease Activity VAS(Baseline, Week 24)
- Change From Baseline in Physicians Global Assessment of Disease Activity VAS(Baseline, Week 24)
- Change From Baseline in C-Reactive Protein (CRP)(Baseline, Week 24)
- Change From Baseline in Disease Activity Score-CRP (DAS28-CRP)(Baseline, Week 24)
- Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score(Baseline, Week 24)
- Change From Baseline in Fatigue Severity Numeric Rating Scale (NRS) Score(Baseline, Week 24)
- Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Scores: Physical Component Summary (PCS)(Baseline, Week 24)
- Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Scores: Mental Component Summary (MCS)(Baseline, Week 24)
- Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA)(Week 24)
- Pharmacokinetics (PK):Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Ixekizumab(All immunogenicity samples post the first Ixekizumab dose (Week 4, 12, 24, 36, and 52) and PK samples collected per dedicated sparse sampling plan (4-5 samples per patient) across Weeks 1 through 24 and Early termination visit (ETV))
- Pharmacokinetics: Area Under the Concentration-Time Curve for Dosing Interval (Tau) at Steady State [AUC(Tau,Steady State)] of Ixekizumab(All immunogenicity samples post the first Ixekizumab dose (Week 4, 12, 24, 36, and 52) and PK samples collected per dedicated sparse sampling plan (4-5 samples per patient) across Weeks 1 through 24 and Early termination visit (ETV))
- Percentage of Participants Achieving ACR 20(Week 52 and Week 156)
- Percentage of Participants Achieving ACR 50(Week 52 and Week 156)