A Dose-Ranging And Efficacy Study of LY2439821 (An Anti-IL-17 Antibody) In Patients With Moderate-To-Severe Psoriasis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 142
- 试验地点
- 1
- 主要终点
- Percentage of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement
研究概览
简要总结
The primary purpose for this study is to help answer the following research questions
- The safety of ixekizumab (LY2439821) and any side effects that might be associated with it.
- Whether ixekizumab can help participants with Psoriasis.
- How much ixekizumab should be given to participants.
详细描述
The study is a Phase 2 study with 3 parts. Part A is a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging design, Part B is an optional, open label extension design and Part C is an additional optional extension period with an open-label design(up to approximately 104 weeks). Approximately 125 participants will be randomized to 1 of 4 ixekizumab groups or to placebo (approximately 25 participants per group) in Part A. Participants will be evaluated for treatment efficacy and the primary endpoint will be evaluated at week 12. Between week 20 and week 32, participants with a less than 75% improvement in their Psoriasis Area and Severity Index (PASI) score compared to baseline will be eligible to begin Part B. Participants in Part B will receive subcutaneous (SC) injections of ixekizumab 120 milligrams (mg) every 4 weeks through week 236. Subsequent to an amendment on May 2012, administration changed to 80 mg every 4 weeks through Week 236. Participants in Part C may receive SC injections of ixekizumab 80 mg every 4 weeks for up to an additional 104 weeks through approximately week 340. Participants who complete Part A, Part B, and Part C will have a total study participation of approximately 344 weeks.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
10 mg Ixekizumab
Part A:
10 milligrams (mg) ixekizumab given subcutaneous (SC) on weeks 0, 2, 4, 8, 12 and 16 for a total of six administrations.
Part B: (optional)
120 mg ixekizumab given SC Q4W. Subsequent to an amendment on May 2012, administration changed to 80 mg Q4W through Week 236.
Part C: (optional)
80 mg ixekizumab given SC Q4W through approximately week 344.
干预措施: Ixekizumab (Biological)
25 mg Ixekizumab
Part A:
25 mg ixekizumab given SC on weeks 0, 2, 4, 8, 12 and 16 for a total of six administrations.
Part B: (optional)
120 mg ixekizumab given SC (Q4W). Subsequent to an amendment on May 2012, administration changed to 80 mg Q4W through Week 236.
Part C: (optional)
80 mg ixekizumab given SC Q4W through approximately week 344.
干预措施: Ixekizumab (Biological)
75 mg Ixekizumab
Part A:
75 mg ixekizumab given SC on weeks 0, 2, 4, 8, 12 and 16 for a total of six administrations.
Part B: (optional)
120 mg ixekizumab given SC Q4W. Subsequent to an amendment on May 2012, administration changed to 80 mg Q4W through Week 236.
Part C: (optional)
80 mg ixekizumab given SC Q4W through approximately week 344.
干预措施: Ixekizumab (Biological)
150 mg Ixekizumab
Part A:
150 mg ixekizumab given SC on weeks 0, 2, 4, 8, 12 and 16 for a total of six administrations.
Part B: (optional)
Administered 120 mg ixekizumab SC Q4W. Subsequent to an amendment on May 2012, administration changed to 80 mg Q4W through Week 236.
Part C: (optional) 80 mg ixekizumab given SC Q4W through approximately week 344.
干预措施: Ixekizumab (Biological)
Placebo
Part A:
Placebo given on weeks 0, 2, 4, 8, 12 and 16 for a total of six administrations.
Part B: (optional) 120 mg ixekizumab given SC Q4W. Subsequent to an amendment on May 2012, administration changed to 80 mg Q4W through Week 236.
Part C: (optional)
80 mg ixekizumab given SC Q4W through approximately week 344.
干预措施: Ixekizumab (Biological)
Placebo
Part A:
Placebo given on weeks 0, 2, 4, 8, 12 and 16 for a total of six administrations.
Part B: (optional) 120 mg ixekizumab given SC Q4W. Subsequent to an amendment on May 2012, administration changed to 80 mg Q4W through Week 236.
Part C: (optional)
80 mg ixekizumab given SC Q4W through approximately week 344.
干预措施: Placebo (Drug)
120 mg Ixekizumab
Part B: (optional)
120 mg ixekizumab given SC every 4 weeks. Subsequent to an amendment on May 2012, administration changed to 80 mg every 4 weeks through Week 236.
Part C: (optional) 80 mg ixekizumab given SC every 4 weeks through approximately week 344.
干预措施: Ixekizumab (Biological)
80 mg Ixekizumab
Part B: (optional)
Subsequent to an amendment on May 2012, administration changed to 80 mg ixekizumab Q4W through Week 236.
Part C: (optional) 80 mg ixekizumab given SC every 4 weeks through approximately week 344.
干预措施: Ixekizumab (Biological)
结局指标
主要结局
Percentage of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement
时间窗: Week 12
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 (none) to 4 (very severe). 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 psoriasis) to 72 (the most severe disease).Participants achieving PASI 75 were defined as having an improvement of ≥75% in the PASI score compared to baseline.
Percentage of PASI Improvement From Baseline to 12 Week Endpoint
时间窗: Baseline to 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 (none) to 4 (very severe). Each area is scored by itself and the scores were 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 psoriasis) to 72 (the most severe disease). Least squares (LS) mean values were calculated using mixed model repeated measures (MMRM) and controlled for baseline as a covariate, visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured.
次要结局
- Percentage of Participants With a Static Physician's Global Assessment (sPGA) Score of Cleared (0) or Minimal (1) With at Least a 2 Point Improvement" at Week 12(Week 12)
- Number of Participants With Treatment Emergent Adverse Events Up to 20 Weeks(Baseline Up to 20 Weeks)
- Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 16(Baseline, Week 16)
- Change From Baseline in 16-Item Quick Inventory of Depressive Symptoms- Self Rated (QIDS-SR16) Total Score at Week 16(Baseline, Week 16)
- Change From Baseline in Patient Global Assessment (PatGA) at Week 12(Baseline, 12 Weeks)
- Change From Baseline in Pain Visual Analog Scale (VAS) at Week 12(Baseline, Week 12)
- Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-S) at Week 16(Baseline, Week 16)
- Number of Participants Who Received Medical Care Measured by Medical Care Resource Utilization (PMRU))(Week 16)
- Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI Q) at Week 16(Baseline, Week 16)
- Change From Baseline in Medical Outcomes Study Short-Form 36 (SF-36) - Physical Component Score (PCS) and Mental Component Score (MCS) at Week 16(Baseline, Week 16)
- Change From Baseline in Nail Psoriasis Severity Index (NAPSI) in Participants With Nail Psoriasis at Week 12(Baseline, Week 12)
- Ixekizumab Systemic Clearance (CL) (Serum Concentrations of Ixekizumab From Baseline Through 32 Weeks)(Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32)
- Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 12(Baseline, Week 12)
- Change From Baseline in Palmoplantar Psoriasis Severity Index (PPASI) in Participants With Palmoplantar Psoriasis at Week 12(Baseline, Week 12)
- Change From Baseline in Scalp Psoriasis Severity Index (PSSI) in Participants With Scalp Psoriasis at Week 12(Baseline, Week 12)
- Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score Total Score at Week 16(Baseline, Week 16)
- Percentage of Participants Who Achieve a 75% Improvement in the Psoriasis Area and Severity Index (PASI 75)(Week 32)
- Percentage of PASI Improvement From Baseline Through 32 Weeks(Baseline Through 32 Weeks)
- Percentage of Participants With Static Physician's Global Assessment (sPGA) of (0,1)(Baseline Up to 240 Weeks)
- Percentage of Participants With a Static Physician's Global Assessment (sPGA) Score of Cleared (0) or Minimal (1) With at Least a 2 Point Improvement(Week 32)
- Change From Baseline in Hospital Anxiety and Depression Scale (HADS)(Baseline Up to 240 Weeks)
- Percentage of Participants With Anti-Ixekizumab Antibodies(Baseline through Week 20)
- Number of Participants With Patient's Global Assessment of Disease Activity (PatGA)(Week 240)
- Change From Baseline in Pain Visual Analog Scale (VAS)(Baseline Up to 240 Weeks)
- Change From Baseline up to 240 Weeks in Scalp Psoriasis Severity Index (PSSI) in Participants With Scalp Psoriasis(Baseline Up to 240 Weeks)
- Percentage of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement(Week 240)
- Change From Baseline in Dermatology Life Quality Index (DLQI)(Baseline Up to 240 Weeks)
- Number of Treatment Emergent Adverse Events up to 344 Weeks(Baseline Up to 344 Weeks)
- Change From Baseline up to 240 Weeks in Nail Psoriasis Severity Index (NAPSI) in Participants With Nail Psoriasis(Baseline Up to 240 Weeks)
- Change From Baseline up to 240 Weeks in Palmoplantar Psoriasis Severity Index (PPASI) in Participants With Palmoplantar Psoriasis(Baseline Up to 240 Weeks)