A Two-part Exploratory Study Combining a Pilot Study in Healthy Subjects and Chronic Spontaneous Urticaria Patients (Part 1) and a Randomized, Subject, Investigator and Sponsor-blinded, Placebo Controlled, Study (Part 2) to Assess the MechAniSm of acTion of ligElizumab (QGE031) in Patients With Chronic uRticaria (MASTER)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Part 1: Wheal and erythema size after skin prick test with several different ciprofloxacin and icatibant concentrations.
研究概览
简要总结
The purpose of the study is to investigate the mechanism of action for ligelizumab (QGE031) treatment in patients with chronic urticaria.
The study has two parts. The study population will consist of approximately 68 male and female healthy volunteers and patients. In Part 1, approximately 20 healthy volunteers and patients with chornic urticaria will be enrolled. In Part 2 approximately 48 patients with chronic urticaria (spontaneous chronic urticaria, cholinergic urticaria or cold urticaria). Part 1 consists of a screening period up 2 weeks and a visit with skin tests; there is no treatment taken in Part 1. Part 2 is randomized, subject, investigator and sponsor blinded. It consists of a screening period up to 4 weeks, a 16 week treatment period and a 12-week follow-up period after last treatment. A follow-up call at Week 32 will be performed via telephone.
详细描述
There are 58 patients out of 68 participants (10 are Healthy Volunteers)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
盲法说明
Part 1 is not masked Part 2 is masked
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers • Healthy male and female subjects in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
- •CSU and CINDU patients (cold and cholinergic urticaria)
- •Part 2: Positive response to challenge test with ciprofloxacin 250 mg/ml or 125 mg/ml, defined as a wheal formation with longest diameter of at least 3 mm and middle perpendicular diameter of at least 2 mm at Day
- •CSU patients
- •Diagnosis of CSU, not adequately controlled with H1-AH at approved doses alone at the time of randomization, as defined by all of the following:
- •UAS7 score (range 0-42) ≥ 16 and HSS7 (range 0-21) ≥ 8 during 7 days prior to randomization
- •CSU for ≥ 6 months CINDU patients (cold and cholinergic urticaria)
- •For patients with cold urticaria: Cold urticaria symptoms persisting for at least 6 months prior to study enrollment and a positive cold urticaria provocation test defined as wheal response to TempTest 4.0® at Day
- •For patients with cholinergic urticaria: Cholinergic urticaria symptoms for at least 6 months prior to enrollment and a positive response in the challenge test defined as a wheal response in the pulse controlled ergometry provocation test (30 minutes bicycle challenge) at Day 1
排除标准
- •Healthy volunteers
- •History of allergies or allergy to the challenge substances including ciprofloxacin, icatibant, other quinolones or excipients of the substances being used in the study.
- •Recent (within the last three years) and/or recurrent history of autonomic dysfunction (e.g. recurrent episodes of fainting, palpitations, etc.).
- •Donation or loss of 450 mL or more blood within eight weeks prior to initial dosing, or longer if required by local regulations.
- •CSU and CINDU patients (cold and cholinergic urticaria)
- •History of allergies or allergy to the challenge substances including ciprofloxacin, icatibant (Part 1 only), other quinolones or excipients of the substances being used in this study.
- •Contraindications to or hypersensitivity to antihistamines (such as fexofenadine, loratadine, cetirizine, rupatadine, bilastine) or epinephrine or any of the ingredients.
- •History or presence of renal disease and/or estimated glomerular filtration (eGFR) rate of < 35 mL/min as calculated by the CKD-EPI formula at Screening.
- •For subjects who enter Part 2: Patients with a history of or a risk of parasite infections (recent stay in tropical/subtropical areas with low hygiene standards). To allow enrollment of a patient at risk perform stool examinations for ova or parasites and demonstrate absence of infection first.
- •Diseases with possible signs and symptoms of urticaria or angioedema such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and hereditary or acquired angioedema (e.g. due to C1 inhibitor deficiency).
- •CSU patients • Clearly defined underlying etiology for chronic urticaria symptoms other than CSU. This includes the following: CSU patients should not have inducible urticaria forms impacting their daily symptoms in a relevant way, such as but not limited to urticaria factitia, cold-, heat-, solar-, pressure-, delayed pressure, aquagenic-, cholinergic-, or contact-urticaria.
- •CINDU patients (cold and cholinergic urticaria)
- •Clearly defined underlying etiology for chronic urticaria symptoms other than CINDU. This includes the following: CINDU patients should not have spontaneous urticaria impacting their symptoms in a relevant way.
- •Other protocol-defined inclusion/exclusion criteria may apply .
研究组 & 干预措施
Ligelizumab
test drug
干预措施: Ligelizumab (Drug)
Placebo
placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Part 1: Wheal and erythema size after skin prick test with several different ciprofloxacin and icatibant concentrations.
时间窗: At Day 1
Size of the wheal and erythema in mm will be measured after the skin prick and intradermal tests are performed. Different dilution steps will be applied (to differentiate Chronic Spontaneous Urticaria patients and healthy controls) for ciprofloxacin and icatibant to determine the conditions to be used in Part 2.
Part 2: Change in wheal size after challenge procedure from Day 1 (pre-dose) to week 16.
时间窗: Day 1 and Week 16
Size of wheal in mm2 after skin prick test and autologous serum skin test will be measured.
次要结局
- Part 2: Urticaria Control Test(Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28)
- Part 2: Weekly Urticaria Activity Score(Throughout the study (to 28 weeks))
- Part 2: Cholinergic Urticaria Activity score(Day 1 to Week 28)
- Part 2: Chronic Urticaria Quality of Life questionnaire(Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28)
- Part 2: Angioedema control test(Day 1, Week 16, Week 28)
- Part 2: Cholinergic Urticaria Quality of Life questionnaire(Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28)
- Part 2: Provocation test for cholinergic patients(Day 1, Week 4, Week 16, Week 28)
- Part 2: Temperature trigger test for cold urticaria patients(Day 1, Week 4, Week 16, Week 28)
- Part 2: Number of patients with adverse events(Throughout the study (to 28 weeks))