Efficacy and Safety Comparison of Brodalumab Versus Guselkumab in Adult Subjects With Moderate-to-severe Plaque Psoriasis and Inadequate Response to Ustekinumab
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- LEO Pharma
- 入组人数
- 113
- 试验地点
- 4
- 主要终点
- Having Psoriasis Area and Severity Index (PASI) 100 Response at Week 16
研究概览
简要总结
The trial investigates the efficacy and safety of brodalumab against guselkumab in treatment for patients with moderate-to-severe plaque psoriasis who still have some remaining symptoms after ustekinumab treatment.
详细描述
Brodalumab is an anti-interleukin 17 receptor A antibody (IL-17RA) and blocks the inflammatory effects of different IL-17 cytokines (IL-17A, IL-17C, IL-17F, IL-17A/F heterodimer, and IL-17E) in the skin. With increasing availability of novel biologics with new targets, the complexity of choosing the appropriate biologic treatment is ever more challenging for physicians. Therefore, the primary objective of this trial is to compare the efficacy of brodalumab versus guselkumab in adult participants with moderate to severe plaque psoriasis and inadequate response to ustekinumab, thereby providing new scientific information that could support decision making in the clinical setting. The study will run approximately 32 weeks for each participant (including a 2- to 4-weeks screening period and a 28-week treatment period), with the primary endpoint measurement at Week 16. Participants receive subcutaneous injections of brodalumab or guselkumab. Dummy injections are also given, so participants and assessors are unaware of which treatment is given.
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, Outcomes Assessor)
盲法说明
Brodalumab (1.5 mL) and guselkumab (1.0 mL) are in pre-filled syringes and packaged open-label. Dummy injections are used for blinding.
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
- •Participant has a diagnosis of plaque psoriasis for at least 6 months before the first administration of investigational medicinal product (IMP) as determined by the investigator.
- •Participant has inadequately controlled plaque psoriasis currently treated with ustekinumab, and fulfils ALL of the following criteria:
- •Ustekinumab administered at least 3 times at or higher than the approved dose or frequency before randomisation.
- •IGA ≥2 at screening and baseline.
- •Absolute PASI >3 at screening and baseline.
- •Participant has no evidence of active tuberculosis according to local standard of care for patients requiring initiation of a biologic treatment. Participants with adequately treated latent tuberculosis, according to local guidelines, are eligible.
排除标准
- •Participant was diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis, or other skin conditions (e.g. eczema) that would interfere with evaluations of the effect of IMP on plaque psoriasis.
- •Participant has clinically important active infections or infestations, chronic, recurrent, or latent infections or infestations, or is immunocompromised (e.g. human immunodeficiency virus).
- •Participant has any systemic disease (e.g. renal failure, heart failure, hypertension, liver disease, diabetes, anaemia) considered by the investigator to be clinically significant and uncontrolled.
- •Participant has a known history of Crohn's disease.
- •Participant has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma.
- •Participant has a history of malignancy within 5 years, except for treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma.
- •Participant has a known history of active tuberculosis.
- •Participant has a history of suicidal behaviour (i.e. 'actual suicide attempt', 'interrupted attempt', 'aborted attempt', or 'preparatory acts or behaviour') based on the Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire at screening or baseline.
- •Participant has any suicidal ideation of severity 4 or 5 ('some intent to act, no plan' or 'specific plan and intent') based on the C-SSRS questionnaire at screening or baseline.
- •Participant has a Patient Health Questionnaire-8 (PHQ-8) score of ≥10, corresponding to moderate to severe depression at screening or baseline.
- •Participant has previously been treated with any anti-interleukin (IL)-17A, anti-IL 17 receptor subunit A, or anti-IL-23 besides ustekinumab.
- •Participant has known or suspected hypersensitivity to any component(s) of the IMPs.
研究组 & 干预措施
Arm 1 (brodalumab + dummy 1)
Participants receive:
- Brodalumab 210 mg (1.5 ml) at Weeks 0, 1, 2, and then every 2 weeks.
- Dummy 1 (placebo 1.0 ml) at Weeks 0, 4, and then every 8 weeks.
干预措施: Brodalumab (Biological)
Arm 1 (brodalumab + dummy 1)
Participants receive:
- Brodalumab 210 mg (1.5 ml) at Weeks 0, 1, 2, and then every 2 weeks.
- Dummy 1 (placebo 1.0 ml) at Weeks 0, 4, and then every 8 weeks.
干预措施: Placebo (Other)
Arm 2 (guselkumab + dummy 2)
Participants receive:
- Guselkumab 100 mg (1.0 ml) at Weeks 0, 4, and then every 8 weeks.
- Dummy 2 (placebo 1.5 ml) at Weeks 0, 1, 2, and then every 2 weeks.
干预措施: Placebo (Other)
Arm 2 (guselkumab + dummy 2)
Participants receive:
- Guselkumab 100 mg (1.0 ml) at Weeks 0, 4, and then every 8 weeks.
- Dummy 2 (placebo 1.5 ml) at Weeks 0, 1, 2, and then every 2 weeks.
干预措施: Guselkumab (Biological)
结局指标
主要结局
Having Psoriasis Area and Severity Index (PASI) 100 Response at Week 16
时间窗: Week 16
Having 100% improvement from baseline in PASI score. The outcome measure is summarized using the least squares mean percentage of subjects having PASI 100 response at Week 16, based on a logistic regression model adjusted for baseline body weight (\<=100 kg,\>100 kg) and baseline PASI score. The PASI is the most widely used tool in clinical practice and clinical trials to assess psoriasis severity and extent. Assessment is done based on the condition of the disease at the time of evaluation, not in relation to the condition at a previous visit. The investigator assesses the severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions (head/neck, trunk, upper extremities, lower extremities) according to a severity scale. The investigator also assesses the extent of psoriasis within each of the 4 body regions. This gives a composite score ranging from 0 to 72, with higher values indicating a more severe/extensive condition.
次要结局
- Time to PASI 90 Response (Summarized as the Cumulative Incidence for Achieving PASI 90 at Each Timepoint, Stratified by Weight)(up to 28 weeks)
- Having IGA of 0 or 1, Assessed Separately at Weeks 16 and 28.(Weeks 16 and 28)
- Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Component Score From Baseline, Assessed Separately at Weeks 4, 8, 16, and 28.(Weeks 4, 8, 16, and 28)
- Time to PASI 100 Response (Summarized as the Cumulative Incidence for Achieving PASI 100 at Each Timepoint, Stratified by Weight)(up to 28 weeks)
- Having Investigator's Global Assessment (IGA) of 0, Assessed Separately at Weeks 16 and 28.(Weeks 16 and 28)
- Having Dermatology Life Quality Index (DLQI) Total Score of 0 or 1, Assessed Separately at Weeks 4, 8, 12, 16, 20, 24, and 28.(Weeks 4, 8, 12, 16, 20, 24, and 28)
- Occurrence of Treatment-emergent Adverse Events (AEs) From Baseline to Week 28.(From baseline to Week 28)
- Having PASI 100 Response, Assessed Separately at Weeks 4, 8, and 28.(Weeks 4, 8, and 28)
- Having PASI 90 Response, Assessed Separately at Weeks 4, 8, 16, and 28.(Weeks 4, 8, 16, and 28)
- Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Physical Component Score From Baseline, Assessed Separately at Weeks 4, 8, 16, and 28.(Weeks 4, 8, 16, and 28)