Randomized, Double-Blinded, Placebo-Controlled, Parallel-Design, Dose-Range Finding Study of Subcutaneous Tildrakizumab (SCH 900222/MK-3222) in Subjects With Moderate-to-Severe Chronic Plaque Psoriasis (Study P05495)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 355
- 主要终点
- Percentage of Participants With a Psoriasis Area and Severity Index (PASI)75 Response at Week 16
研究概览
简要总结
This is a response-driven study of tildrakuzumab for the treatment of moderate to severe chronic plaque psoriasis. The primary study hypothesis is that one or more doses of tildrakizumab will be superior to placebo for the treatment of psoriasis.
详细描述
Each participant will be enrolled in the trial for approximately 72-76 weeks. Each participant will receive assigned treatment at Weeks 0 and 4 in Part I. At Week 16, the dosage of treatment the patient is assigned to may be adjusted based on the Psoriasis Area and Severity Index (PASI) 75 response (responder vs non-responder). Participants will receive study medication once every 12 weeks during Part 2 (Weeks 16 to 52); no participants will receive placebo in Part 2. Part 3 is an observational period and each subject will continue to be monitored on a monthly basis through Week 72. Subjects will not receive any study medication during Part 3.
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
- •Adult participants (≥18 years of age) with a diagnosis of moderate-to-severe chronic plaque psoriasis (defined by ≥10% body surface area [BSA] involvement, "moderate" or greater score on the Physician's Global Assessment [PGA] scale, and PASI score ≥12 at Baseline)
- •Participants must have a diagnosis of predominantly plaque psoriasis for ≥6 months (as determined by interview and confirmation of diagnosis through physical examination by investigator) and be considered candidates for phototherapy or systemic therapy. Participants with psoriatic arthritis may be included in the study
排除标准
- •Nonplaque forms of psoriasis specifically erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis
- •Participants who will require oral or injectable corticosteroids during the trial
- •Presence of any infection requiring treatment with systemic antibiotics within 2 weeks prior to Screening, or serious infection (eg, pneumonia, cellulitis, bone or joint infections) requiring hospitalization or treatment with intravenous antibiotics within 8 weeks prior to Screening
- •Participants with evidence of active or untreated latent tuberculosis (TB) according to Screening criteria specified in the protocol. (Prophylactic treatment for latent TB as per local guidelines must be initiated at least 4 weeks prior to treatment with study medication)
- •Previous exposure to any agents targeting interleukin-12 (IL-12) and/or Interleukin-23 (IL-23)
- •Participants with prior exposure to two or more tumor necrosis factor (TNF) antagonists with discontinuation due to lack of efficacy.
研究组 & 干预措施
Part 1: Tildrakizumab 5 mg
Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4
干预措施: tildrakizumab (Biological)
Part 1: Tildrakizumab 25 mg
Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4
干预措施: tildrakizumab (Biological)
Part 1: Tildrakizumab 100 mg
Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4
干预措施: tildrakizumab (Biological)
Part 1: Tildrakizumab 200 mg
Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4
干预措施: tildrakizumab (Biological)
Part 1: Placebo
Participants receive placebo, SC, at Weeks 0 and 4
干预措施: Placebo (Drug)
Part 2: Tildrakizumab 5 mg
Participants receive tildrakizumab 5 mg, SC, every 12 weeks for up to 36 weeks
干预措施: tildrakizumab (Biological)
Part 2: Tildrakizumab 25 mg
Participants receive tildrakizumab 25 mg, SC, every 12 weeks for up to 36 weeks
干预措施: tildrakizumab (Biological)
Part 2: Tildrakizumab 100 mg
Participants receive tildrakizumab 100 mg, SC, every 12 weeks for up to 36 weeks
干预措施: tildrakizumab (Biological)
Part 2: Tildrakizumab 200 mg
Participants receive tildrakizumab 200 mg, SC, every 12 weeks for up to 36 weeks
干预措施: tildrakizumab (Biological)
结局指标
主要结局
Percentage of Participants With a Psoriasis Area and Severity Index (PASI)75 Response at Week 16
时间窗: Week 16
The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease). PASI 75 response was defined as \>=75% improvement in PASI score when compared to the baseline score.
Number of Participants Experiencing Adverse Events
时间窗: Up to 72 weeks
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
Number of Particpants Discontinuing Study Treatment Due to Adverse Events
时间窗: Up to 52 weeks
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. Participants may be discontinued from study drug due to adverse events, but remain on the study.
次要结局
- PASI 75 Response Rate by Time(Up to 16 Weeks)
- Percentage of Participants With Physician's Global Assessment (PGA) of "Cleared" or "Minimal" at Week 16(Week 16)
- Percentage of Participants With PASI 90 Response at Week 16(Week 16)
- Percentage of Participants With PASI 100 Response at Week 16(Week 16)
- Mean Change From Baseline in PASI Score at Weeks 12 and 16(Baseline and Weeks 12 and 16)
- Percentage of Participants With a PASI 75 Response at Week 12(Week 12)
- Percentage of Participants Achieving a >=5 Point Reduction in DLQI at Week 16(Week 16)
- Percentage of Participants With PASI 50 Response at Week 16(Week 16)
- Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16(Week 16)
- Percentage of Participants Achieving DLQI Score of 0 or 1 at Week 16(Week 16)