NCT04833855已完成2 期
A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose-Ranging, Phase 2b Study to Evaluate Efficacy and Safety of Tezepelumab for the Treatment of Chronic Spontaneous Urticaria
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 183
- 试验地点
- 81
- 主要终点
- Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Week 16
研究概览
简要总结
The primary objective of this study is to evaluate the effect of tezepelumab on improvement in the Urticaria Activity Score over 7 days (UAS7).
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent must be obtained prior to participation in the study.
- •Male and female participants ≥ 18 years and ≤ 80 years of age at the time of screening.
- •Chronic spontaneous urticaria (CSU) diagnosis for ≥ 6 months at the time of screening.
- •CSU inadequately controlled by second generation H1-antihistamines (sgAH) at enrollment, as defined by all of the following:
- •The presence of itch and hives for >= 6 consecutive weeks at any time prior to screening visit 2
- •Failure to respond to an sgAH (up to 4 times the approved dose)
- •Urticaria Activity Score over 7 days (UAS7) (range 0-42) >= 16 and Hives Severity Score over 7 days (HSS7) (range 0-21) >= 8 during the 7 days prior to enrollment
- •Participant with CSU who discontinued, is intolerant to, or was an inadequate responder to anti-IgE therapies despite being treated with omalizumab 300 mg every 4 weeks (Q4W) for 6 months or higher doses of omalizumab > 2 months or another anti-IgE therapy. Note: This criterion is only applicable for anti-IgE-experienced participants.
- •Participant willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedules.
- •Subject must have been on a sgAH at approved or increased doses (up to 4x the approved dose) for treatment of CSU for at least 3 consecutive days immediately prior to the day -14 screening visit (screening visit 2) and must have documented current use on the day of screening visit 1
排除标准
- •Disease related, including but not limited to:
- •Urticaria is solely due to inducible urticaria
- •Active dermatologic diseases (or conditions) other than chronic urticaria, with urticaria wheals or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency)
- •Any other active skin disease associated with chronic itching that might influence, in the investigator's opinion, the study evaluations and results (eg, atopic dermatitis, dermatitis herpetiformis, senile pruritus, etc.)
- •History of a clinically significant infection within 28 days prior to day 1 that, in the opinion of the investigator or medical monitor, might compromise the safety of the participant in the study, interfere with evaluation of the investigational product, or reduce the participants ability to participate in the study.
- •Evidence of active tuberculosis (TB) (in the opinion of the investigator), either treated or untreated, or a positive purified protein derivative (PPD) or QuantiFERON-TB Gold Plus (QFT-Plus) test for TB during screening.
- •History of malignancy, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy ≥ 12 months prior to screening or other malignancies treated with apparent success with curative therapy ≥ 5 years prior to screening visit
- •Subject is unable to complete an electronic patient diary or complete questionnaires, or does not meet the required level of compliance with the eDiary during the 14 days sgAH stabilization period
- •Other medical conditions
- •History or evidence of severe depression, schizophrenia, previous suicide attempts, or suicidal ideation.
- •Prior/concomitant therapy, including but not limited to:
- •Treatment with any biologic products (eg, omalizumab, ligelizumab) within 4 months or 5 half-lives (whichever is longer) prior to screening visit 1
- •Routine (daily or every other day for 5 or more consecutive days) use of systemic corticosteroids, systemic hydroxychloroquine, methotrexate, cyclosporine A, cyclophosphamide, tacrolimus, azathioprine, and mycophenolate mofetil within 30 days prior to screening visit
- •Major surgery within 8 weeks prior to screening visit 1 or planned inpatient surgery or hospitalization during the study period.
- •Receipt of Ig or blood products within 30 days prior to screening visit
- •Vaccination with a live or attenuated vaccine within 30 days prior to screening visit
- •Receipt of COVID-19 vaccines and inactive/killed vaccinations (eg, inactive influenza) are allowed, provided the vaccinations are not administered within 7 days before or after any study dosing visit.
- •Known hypersensitivity, including severe hypersensitivity reactions and/or history of anaphylactic shock, to any of the products or components to be administered during dosing or to products of similar chemical classes (ie, to murine, chimeric, or human antibodies.
研究组 & 干预措施
Group 7: Tezepelumab Dose 2
Experimental
Participants previously treated with anti-IgE therapies will receive tezepelumab.
干预措施: Tezepelumab Dose 2 (Biological)
Group 1: Omalizumab
Active Comparator
Participants naive to anti-IgE therapies will receive omalizumab.
干预措施: Omalizumab (Biological)
Group 2: Placebo
Placebo Comparator
Participants naive to anti-IgE therapies will receive a placebo.
干预措施: Placebo (Biological)
Group 3: Tezepelumab Dose 1
Experimental
Participants naive to anti-IgE therapies will receive tezepelumab.
干预措施: Tezepelumab Dose 1 (Biological)
Group 4: Tezepelumab Dose 2
Experimental
Participants naive to anti-IgE therapies will receive tezepelumab.
干预措施: Tezepelumab Dose 2 (Biological)
Group 5: Placebo
Placebo Comparator
Participants previously treated with anti-IgE therapies will receive a placebo.
干预措施: Placebo (Biological)
Group 6: Tezepelumab Dose 1
Experimental
Participants previously treated with anti-IgE therapies will receive tezepelumab.
干预措施: Tezepelumab Dose 1 (Biological)
结局指标
主要结局
Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Week 16
时间窗: Baseline and Week 16
The UAS is a CSU-specific patient-reported outcome measure with 2 components: Hives Severity Score (HSS) for number of wheals and an Itch Severity Score (ISS) for itch intensity, and are each scored from 0 (no wheals, no itch) to 3 (\>50 wheals, severe itch) for the previous 24 hours. The HSS and ISS are combined to give a daily UAS ranging from 0 to 6. The sum of the daily UAS over a 7-day period provides the UAS7, from 0 (no symptoms) to 42 (severe urticaria). The least squares mean (LSM) estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline UAS7, treatment, study week and the interaction between treatment and study week. A negative change from baseline indicates an improvement in urticaria activity.
次要结局
- Number of Participants With a Change From Baseline in HSS7 of ≤ -5.5 (Minimal Important Difference)(Baseline and Week 16)
- Change From Baseline in ISS Over 7 Days (ISS7) at Week 16(Baseline and Week 16)
- Number of Participants With a Change From Baseline in UAS7 of ≤ -10 (Minimal Important Difference)(Baseline and Week 16)
- Number of Participants With a UAS7 of ≤ 6 (Minimal Residual Disease) at Week 16(Week 16)
- Number of Participants With a Change From Baseline in ISS7 of ≤ -5 (Minimal Important Difference)(Baseline and Week 16)
- Number of Cumulative Days of sgAH Rescue Medication Use From Baseline to Week 16(Baseline to Week 16)
- Serum Concentration of Tezepelumab(Week 1 pre-dose, Weeks 2, 4, 8, 12, 16, 24, and 32)
- Change From Baseline in HSS Over 7 Days (HSS7) at Week 16(Baseline and Week 16)
- Number of Participants With ISS7 = 0 at Week 16 (Complete Resolution)(Week 16)
- Change From Baseline in SQS7: Sum of Average Daily Q1 - Q3 at Week 16(Baseline and Week 16)
- Change From Baseline in Weekly Angioedema Activity Score (AAS7) at Week 16(Baseline and Week 16)
- Number of Participants With an AECT Score = 16 at Week 16 (Complete Control)(Baseline and Week 16)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Day 1 Week 1 to Week 32, up to 32 weeks)
- Change From Baseline in the Angioedema Quality of Life Questionnaire (AE-QoL) at Week 16(Baseline and Week 16)
- Number of Participants With a UAS7 = 0 at Week 16 (Complete Response)(Week 16)
- Number of Participants With HSS7 = 0 at Week 16 (Complete Resolution)(Week 16)
- Change From Baseline in Weekly Sleep Quality Score (SQS7): Sum of Daily SQS at Week 16(Baseline and Week 16)
- Change From Baseline in Urticaria Control Test (UCT) Score at Week 16(Baseline and Week 16)
- Change From Baseline in Weekly Sleep Interference Score (SIS7) at Week 16(Baseline and Week 16)
- Number of Cumulative Weeks That Participants Achieved AAS7 = 0 at Week 16 (Angioedema Occurrence Free)(Baseline to Week 16)
- Change From Baseline in the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Week 16(Baseline and Week 16)
- Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 16(Baseline and Week 16)
- Change From Baseline in the Angioedema Control Test (AECT) Score at Week 16(Baseline and Week 16)
- Change From Baseline in the Work Productivity and Activity Impairment Questionnaire: Chronic Urticaria (WPAI-CU) Score at Week 16(Baseline and Week 16)
研究者
研究点 (81)
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