A Randomized, Double-blind, Placebo-controlled, Multi-center, Parallel-group Study of Dupilumab in Patients With Chronic Inducible Cold Urticaria Who Remain Symptomatic Despite the Use of H1-antihistamine Treatment
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 82
- 试验地点
- 33
- 主要终点
- Percentage of Participants With Negative Ice Cube Provocation Test at Week 24
研究概览
简要总结
Primary Objective:
To demonstrate the efficacy of dupilumab in adult and adolescent participants with primary acquired chronic inducible cold urticaria (ColdU) who remain symptomatic despite the use of an H1-antihistamine
Secondary Objectives:
To demonstrate the efficacy of dupilumab on primary acquired chronic inducible ColdU disease control To demonstrate the efficacy of dupilumab on primary acquired chronic inducible ColdU local signs and symptoms (hives/wheals, itch, burning sensation and pain) after provocation test To demonstrate the efficacy of dupilumab on primary acquired chronic inducible ColdU disease activity To demonstrate improvement in health-related quality-of-life and overall disease status and severity To evaluate the ability of dupilumab in reducing the proportion of participants who require rescue therapy To evaluate the proportion of participants with cold exposure triggered urticaria To evaluate safety outcome measures To evaluate immunogenicity of dupilumab
详细描述
The duration of study for each participant included 2-4 weeks of screening period, 24 weeks of treatment period and 12 weeks of post treatment period.
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
- 12 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant had to be ≥12 years to 80 years of age inclusive at the time of signing the informed consent
- •Participants who had a diagnosis of primary acquired chronic inducible ColdU defined as recurrence of itchy wheals and/or angioedema due to cold for longer than 6 weeks prior to screening visit (Visit 1)
- •Participants with positive ice cube provocation test, ie, presenting at least a confluent hive/wheal on the exposed skin area, at the screening visit (Visit 1) and randomization visit (Visit 2)
- •Participants meeting at least 1 of the following criteria despite regular/daily or as needed use of H1-antihistamine (AH):
- •Urticaria Control Test (UCT) (4 item) <12 at the screening visit (Visit 1) and randomization visit (Visit 2)
- •Within 6 months prior to the screening visit, documented medical history of cold exposure triggered anaphylaxis or oropharyngeal edema
- •Within 6 months prior to the screening visit, documented medical history of cold exposure triggered urticaria requiring emergency medical care visit or treatment with epinephrine
- •Participants using a study defined H1-antihistamine regularly/daily or as needed for primary acquired chronic inducible cold urticaria
- •Body weight ≥30 kg
排除标准
- •Participants were excluded from the study if any of the following criteria applied:
- •Clearly defined underlying etiology for urticaria other than primary acquired chronic inducible ColdU
- •Presence of skin morbidities other than cold urticaria that may interfere with the assessment of the study outcomes
- •Active atopic dermatitis
- •Severe concomitant illness(es) that, in the investigator's judgment, would have adversely affected the patient's participation in the study
- •Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated.
- •Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection
- •Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the screening visit and during the screening period
- •Known or suspected immunodeficiency
- •Active malignancy or history of malignancy within 5 years before the baseline visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin
- •History of systemic hypersensitivity or anaphylaxis to any other biologic therapy or any of its excipients.
- •Participation in prior dupilumab clinical study, or have been treated with commercially available dupilumab.
- •The above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Dupilumab
Dose regimens, on top of regular or as needed non-sedating H1-antihistamine
干预措施: Dupilumab SAR231893 (Drug)
Dupilumab
Dose regimens, on top of regular or as needed non-sedating H1-antihistamine
干预措施: Non sedating H1-antihistamine (Drug)
Matched Placebo
Placebo, on top of regular/as needed non-sedating H1-antihistamine
干预措施: Placebo (Drug)
Matched Placebo
Placebo, on top of regular/as needed non-sedating H1-antihistamine
干预措施: Non sedating H1-antihistamine (Drug)
结局指标
主要结局
Percentage of Participants With Negative Ice Cube Provocation Test at Week 24
时间窗: Week 24
The ice cube provocation test is the most frequently used provocation method for cold urticaria (ColdU). A negative ice cube provocation test was defined as the absence of confluent hives/wheal at the entire skin site of exposure after ice cube provocation test. Ice cube was applied on forearm skin for 5 minutes. Provocation test reading time was 10 minutes after removal of ice cube.
次要结局
- Change From Baseline in Cold Urticaria Signs and Symptoms Severity Scale Score at Week 24(Baseline, Week 24)
- Percentage of Participants With Cold Exposure Triggered Urticaria That Required Hospitalization/Emergency Medical Care Visit or Treatment With Epinephrine(From first IMP administration (Day 1) up to 14 weeks after last IMP administration (i.e., up to Week 36))
- Change From Baseline in Local Skin Burning Sensation Scale Score at Weeks 12 and 24(Baseline, Week 12 and Week 24)
- Percentage of Participants With Urticaria Control Test Score >=12 at Week 24(Week 24)
- Change From Baseline in Local Wheal Intensity Likert Scale Score at Weeks 12 and 24(Baseline, Week 12 and Week 24)
- Change From Baseline in Local Itch Severity Scale Score at Weeks 12 and 24(Baseline, Week 12 and Week 24)
- Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) Scale Scores at Week 24(Baseline, Week 24)
- Percentage of Participants Receiving Rescue Therapy for Primary Acquired Chronic Inducible Cold Urticaria(From first investigational medicinal product (IMP) administration (Day 1) up to Week 24)
- Number of Participants With Treatment-emergent Antidrug Antibodies (ADA) Response(From first IMP administration (Day 1) up to 14 weeks after last IMP administration (i.e., up to Week 36))
- Percentage of Participants With an Improvement of >=3 Points From Baseline in Urticaria Control Test Score at Week 24(Baseline to Week 24)
- Change From Baseline in Percentage of Cold Urticaria Sign and Symptom-Free Days at Week 24(Baseline, Week 24)
- Change From Baseline in Cold Urticaria Quality of Life (ColdU-QoL) Scale Score at Week 24(Baseline, Week 24)
- Change From Baseline in Urticaria Control Test (UCT) Scale Scores at Week 24(Baseline to Week 24)
- Change From Baseline in Local Pain Severity Scale Score at Weeks 12 and 24(Baseline, Week 12 and Week 24)
- Percentage of Participants With Negative Ice Cube Provocation Test at Week 12(Week 12)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(From first IMP administration (Day 1) up to 14 weeks after last IMP administration (i.e., up to Week 36))