A Multicenter Study With a Randomized, Double-Blind, Placebo-Controlled Induction Dosing Period Followed by a Randomized Withdrawal Maintenance Dosing Period to Evaluate the Efficacy and Safety of Mirikizumab in Patients With Moderate-to-Severe Plaque Psoriasis OASIS-1
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 530
- 试验地点
- 69
- 主要终点
- Percentage of Participants With a Static Physician's Global Assessment of (sPGA) (0,1) With at Least a 2-point Improvement From Baseline
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of mirikizumab in participants with moderate to severe 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
- Double (Participant, Investigator)
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 an investigator confirmed diagnosis of chronic psoriasis vulgaris for at least 6 months prior to baseline and meet the following criteria:
- •plaque psoriasis involving ≥10% BSA and absolute PASI score ≥12 in affected skin at screening and baseline
- •sPGA score of ≥3 at screening and baseline
- •Candidate for systemic therapy and/or phototherapy for psoriasis.
排除标准
- •Have an unstable or uncontrolled illness, including but not limited to a cerebro-cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurologic disease or abnormal laboratory values at screening, that in the opinion of the investigator, would potentially affect participant safety within the study or of interfering with the interpretation of data.
- •Breastfeeding or nursing women.
- •Have had serious, opportunistic, or chronic/recurring infection within 3 months prior to screening.
- •Have received a Bacillus Calmette-Guerin (BCG) vaccination within 12 months or received live vaccine(s) (including attenuated live vaccines) within 12 weeks of baseline or intend to receive either during the study.
- •Have any other skin conditions (excluding psoriasis) that would affect interpretation of the results.
- •Have received systemic nonbiologic psoriasis therapy or phototherapy within 28 days prior to baseline.
- •Have received topical psoriasis treatment within 14 days prior to baseline.
- •Have received anti-tumor necrosis factor (TNF) biologics, or anti-interleukin (IL)-17 targeting biologics within 12 weeks prior to baseline.
- •Have previous exposure to any biologic therapy targeting IL-23 (including ustekinumab), either licensed or investigational.
研究组 & 干预措施
Mirikizumab
Induction Period:
Participants received 250 milligrams (mg) mirikizumab administered subcutaneously (SC) every 4 weeks (Q4W).
Maintenance Period:
Participants received one of the four options below:
Placebo administered SC every 8 weeks (Q8W) for responders (≥PASI 90).
125 mg mirikizumab administered SC Q8W for responders (≥PASI 90).
250 mg mirikizumab administered SC Q8W for responders (≥PASI 90).
250 mg mirikizumab administered SC Q8W for non-responders (<PASI 90).
干预措施: Mirikizumab (Drug)
Placebo
Induction Period: Participants received placebo administered SC Q4W.
Maintenance Period:
Participants received one of the two options below:
Placebo administered SC Q8W for responders (≥PASI 90).
250 mg mirikizumab administered SC Q4W during week 16 to week 32 and Q8W during week 40 and 48 for non-responders (< PASI 90).
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With a Static Physician's Global Assessment of (sPGA) (0,1) With at Least a 2-point Improvement From Baseline
时间窗: Week 16
The sPGA is the physician's determination of the participant's psoriasis (PsO) lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's PsO 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 a ≥90% Improvement From Baseline in Psoriasis Area and Severity Score (PASI 90)
时间窗: Week 16
PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. 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 PsO) to 72 (the most severe disease).
次要结局
- Percentage of Participants With ≤1% of Body Surface Area (BSA) With Psoriasis Involvement(Week 16)
- Percentage of Participants With a Psoriasis Symptoms Scale (PSS) Symptoms Score of 0 in Those With a PSS Symptoms Score ≥1 at Baseline(Week 16)
- Percentage of Participants Achieving a Dermatology Life Quality Index (DLQI) Total Score of (0,1) With at Least a 5-Point Improvement (Reduction) From Baseline in Participants With a Baseline DLQI Total Score ≥5(Week 16)
- Percentage of Participants Maintaining Clinical Response (PASI 90) After Re-randomization at the Start of the Randomized Withdrawal Period(Week 52)
- Change in Palmoplantar Psoriasis Severity Index (PPASI) Total Score in Participants With Palmoplantar Involvement at Baseline(Week 16)
- Percentage of Participants Achieving a ≥75% Improvement From Baseline in PASI (PASI 75)(Week 16)
- Percentage of Participants Achieving a ≥100% Improvement From Baseline in Psoriasis Area and Severity Score (PASI 100)(Week 16)
- Change in Psoriasis Scalp Severity Index (PSSI) Total Score in Participants With Scalp Involvement at Baseline(Week 16)
- Change in Nail Psoriasis Severity Index (NAPSI) Total Score in Participants With Fingernail Involvement at Baseline(Week 16)
- Change From Baseline on the Short Form (SF)-36 Physical Component Summary (PCS)(Baseline, Week 16)
- Change From Baseline on the SF-36 Mental Component Summary (MCS)(Baseline, Week 16)
- Percentage of Participants With Patient's Global Assessment of Psoriasis (PatGA (0,1)) and >=2 Improvement From Baseline(Baseline, Week 16)
- Change From Baseline on the Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI-PSO)(Baseline, Week 16)
- Change From Baseline in Quick Inventory of Depressive Symptomology (QIDS-SR16) Total Score in Those With a Baseline QIDS-SR16 Total Score ≥11(Baseline, Week 16)
- Percentage of Participants Achieving a Dermatology Life Quality Index (DLQI) (0,1)(Week 16)
- Induction Period: Pharmacokinetics (PK): Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Mirikizumab at Week 16(Week 16: Day 113)