A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Efficacy and Safety of LY2439821 to Etanercept and Placebo in Patients With Moderate-to-Severe Plaque Psoriasis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,224
- 试验地点
- 1
- 主要终点
- Percentage of Participants With a Static Physician Global Assessment (sPGA) of (0,1) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: Static Physician Global Assessment [sPGA])
研究概览
简要总结
This study will assess the safety and efficacy of ixekizumab (LY2439821) compared to etanercept and placebo in participants with moderate to severe chronic plaque psoriasis.
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
- •Present with chronic plaque psoriasis based on a confirmed diagnosis of chronic plaque psoriasis for at least 6 months prior to first dose of study drug
- •At least 10% Body Surface Area (BSA) of psoriasis at screening and at first dose of study drug
- •Static Physician Global Assessment (sPGA) score of at least 3 and Psoriasis Area and Severity Index (PASI) score of at least 12 at screening and at first dose of study drug
- •Candidate for phototherapy and/or systemic therapy
- •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
排除标准
- •Pustular, erythrodermic, and/or guttate forms of psoriasis
- •History of drug-induced psoriasis
- •Prior use of etanercept
- •Clinically significant flare of psoriasis during the 12 weeks prior to randomization
- •Concurrent or recent use of any biologic agent
- •Received non-biologic systemic psoriasis therapy or phototherapy (including psoralens and ultraviolet A [PUVA], ultraviolet B [UVB]) within the previous 4 weeks; or had topical psoriasis treatment within the previous 2 weeks prior to randomization
- •Cannot avoid excessive sun exposure or use of tanning booths for at least 4 weeks prior to randomization and during the study
- •Have participated in any study with interleukin 17 (IL-17) antagonists, including ixekizumab
- •Serious disorder or illness other than plaque psoriasis
- •Serious infection within the last 3 months
- •Breastfeeding or nursing (lactating) women
研究组 & 干预措施
80 mg ixekizumab Dosing Regimen 1
Administered by two 80 mg subcutaneous (SC) injections at Week 0, then one 80 mg SC injection per Dosing Regimen 1 until Week 12. At Week 12, ixekizumab responders are re-randomized to placebo, Dosing Regimen 2 or Dosing Regimen 3. Ixekizumab non-responders are assigned to Dosing Regimen 2.
干预措施: 80 mg ixekizumab Dosing Regimen (Drug)
80 mg ixekizumab Dosing Regimen 2
Administered by two 80 mg SC injections at Week 0, then one 80 mg SC injection per Dosing Regimen 2 until Week 12. At Week 12, ixekizumab responders are re-randomized to placebo, Dosing Regimen 2 or Dosing Regimen 3. Ixekizumab non-responders are assigned to Dosing Regimen 2.
干预措施: 80 mg ixekizumab Dosing Regimen (Drug)
80 mg ixekizumab Dosing Regimen 3
Dosing Regimen 3 is not used until Week 12. At Week 12, ixekizumab responders re-randomized to this arm will receive Dosing Regimen 3.
干预措施: 80 mg ixekizumab Dosing Regimen (Drug)
50 mg etanercept
Administered by one 50 mg SC injection twice weekly starting at Week 0 up to Week 12. At Week 12, etanercept responders are assigned to placebo, and nonresponders to Dosing Regimen 2.
干预措施: 50 mg etanercept (Drug)
Placebo for ixekizumab
Placebo for ixekizumab administered by two SC injections at Week 0, then one SC injection per Dosing Regimen 1 until Week 12. At Week 12, placebo responders are assigned to placebo, and nonresponders to Dosing Regimen 2. Placebo for etanercept administered by one SC injection twice weekly starting at Week 0 up to Week 12 was used to blind etanercept injections for Dosing Regimen 1, Dosing Regimen 2, and Placebo Comparator groups.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With a Static Physician Global Assessment (sPGA) of (0,1) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: Static Physician Global Assessment [sPGA])
时间窗: Week 12
The sPGA is the physician's determination of the participant's Psoriasis (Ps) lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's Ps was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of "0" or "1" with at least a 2-point improvement from baseline.
Percentage of Participants Achieving Psoriasis Area and Severity Index (PASI) ≥75% (PASI75) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: Psoriasis Area and Severity Index [PASI])
时间窗: Week 12
The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region \* area score \* weighing factor (head \[0.1\], upper limbs \[0.2\], trunk \[0.3\], lower limbs \[0.4\]). Overall scores range from 0 (no Ps) to 72 (the most severe disease). Participants achieving PASI75 were defined as having an improvement of ≥75% in the PASI score compared to baseline.
次要结局
- Percentage of Participants Achieving an sPGA (0) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: [sPGA])(Week 12)
- Percentage of Participants Achieving PASI 90% (PASI90) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: [PASI])(Week 12)
- Percentage of Participants Achieving PASI 100% (PASI100)(Week 12)
- Percentage of Participants Maintaining an sPGA (0,1) From Week 12 After Re-randomization at Start of Maintenance Dosing Period to Week 60(Week 60)
- Change From Baseline in Patient's Global Assessment (PatGA) of Disease Severity(Baseline, 12 weeks)
- Change From Baseline Psoriasis Scalp Severity Index (PSSI) Score(Baseline, Week 12)
- Change From Baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores(Baseline, Week 12)
- Change From Baseline in Nail Psoriasis Severity Index (NAPSI)(Baseline, Week 12)
- Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score(Baseline, Week 12)
- Percentage of Participants With Itching Severity (Itch Numeric Rating Scale [NRI]) Score ≥4 Point Reduction From Baseline(Week 12)
- Change From Baseline in Percent of Body Surface Area (BSA) Involvement of Psoriasis(Baseline, Week 12)
- Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO)(Baseline, Week 12)
- Percentage of Participants Achieving Palmoplantar PASI (PPASI) of ≥50% (PPASI50), ≥75% (PPASI75) or 100% (PPASI100) Improvement(Week 12)
- Percentage of Participants With Anti-Ixekizumab Antibodies(Baseline to Week 12)
- Change From Baseline in Dermatology-Specific Quality of Life Index (DLQI) Total Score (Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes [PRO])(Baseline, Week 12)